Mitchel L. Zoler, PhD

TORONTO – Among postmenopausal women with osteoporosis, treatment with zoledronic acid had a similar effect on fracture reduction regardless of whether women had a low, intermediate, or high baseline fracture risk, based on a post-hoc analysis of nearly 3,900 women who received the agent in the drug’s pivotal trial for fracture prevention.

The analysis showed that rates of vertebral fractures and total clinical fractures fell by roughly similar amounts, regardless of the women’s baseline fracture risk, with annual injection of zoledronic acid during 3 years of treatment and follow-up.

The rate of hip fractures showed a greater reduction in women who entered the study in the lowest tertile for fracture risk relative to the placebo group than in women with intermediate or high risk, but this difference failed to reach statistical significance, Jane A. Cauley, Dr.P.H. said at the meeting.

The message is that postmenopausal women with osteoporosis should feel comfortable starting zoledronic acid treatment regardless of the severity of their fracture risk at baseline, said Dr. Cauley, professor of epidemiology at the University of Pittsburgh. It is not necessary to target treatment to women with an especially elevated fracture risk, such as those with a high FRAX (Fracture Risk Assessment Tool) score, she explained.

The results support a prior report with similar findings from the Women’s Health Initiative on the impact of estrogen or estrogen plus progesterone on fracture risk (JAMA 2003;290:1729-38). However, results from another prior study on the impact of clodronate on fracture risk suggested that osteoporotic women with the highest baseline fracture risk stood to gain the most from bisphosphonate treatment (Osteoporosis Int. 2009;20:811-17).

The current analysis used data collected in the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) pivotal fracture trial, which randomized 7,765 postmenopausal women to either an annual infusion with 5 mg zoledronic acid or placebo for 3 years (N. Engl. J. Me 2007;356:1809-22). Assessment of the study’s primary end point showed that annual treatment with zoledronic acid significantly cut the rate of vertebral and hip fractures as well as total clinical fractures.

To perform the post-hoc analysis, Dr. Cauley and her associates rated the baseline fracture risk of the 3,889 women randomized to receive zoledronic acid using a modification of the Fracture Index developed for the Study of Osteoporotic Fractures (SOF) (Osteoporosis Int. 2001;12:519-28). The modification calculated a woman’s baseline fracture risk using five of the seven variables of the SOF tool available in the HORIZON records: age, femoral neck bone mineral density T score, clinical fracture history, weight, and smoking status. The two SOF tool elements not available were maternal history of hip fracture and the use of arms to stand from a chair.

Analyses by Dr. Cauley and her associates using SOF data showed that calculating a fracture risk score with the five elements had a 98% correlation with the seven-item score, as well as a 64% correlation with women’s FRAX scores. To further confirm the validity of the modified SOF score, they calculated scores for the 3,876 women enrolled in the placebo arm of HORIZON. During 3 years of follow-up, the rate of total fractures per 1,000 person-years was 30, 35, and 45 respectively in the low-, intermediate-, and high-risk tertiles. Overall, for every 1-point rise in the modified SOF score, the risk of a fracture among the placebo women during follow-up rose by 11%, a statistically significant difference.

The researchers then assessed follow-up fracture rates among the low-, intermediate-, and high-risk women who received zoledronic acid. The rate of morphometric vertebral fractures compared with the placebo group fell by 80% in the low-risk tertile of women, by 69% in the intermediate-risk tertile, and by 68% in the high-risk women, differences that were not statistically significant.

The rate of all clinical fractures dropped by 35% in the low-risk women, 38% in the intermediate-risk women, and 30% in the high-risk women, also nonsignificant differences.

The rate of hip fractures with zoledronic acid treatment compared with placebo fell by 71% in the low-risk women, 41% in intermediate-risk women, and 22% in high-risk women. These between-group differences just missed being statistically significant (P = .06).

Additional analyses also showed that the zoledronic acid treatment consistently increased bone mineral density, and reduced two biomarkers of osteoporosis, procollagen type I N-propeptide and C-telopeptide cross-linked collagen, compared with the placebo group, regardless of baseline fracture risk, Dr. Cauley said.

HORIZON was supported by Novartis, the company that markets zoledronic acid (Reclast). Dr. Cauley said that she has received research funding from and has served as a consultant to Novartis.

TORONTO – Among postmenopausal women with osteoporosis, treatment with zoledronic acid had a similar effect on fracture reduction regardless of whether women had a low, intermediate, or high baseline fracture risk, based on a post-hoc analysis of nearly 3,900 women who received the agent in the drug’s pivotal trial for fracture prevention.

The analysis showed that rates of vertebral fractures and total clinical fractures fell by roughly similar amounts, regardless of the women’s baseline fracture risk, with annual injection of zoledronic acid during 3 years of treatment and follow-up.

The rate of hip fractures showed a greater reduction in women who entered the study in the lowest tertile for fracture risk relative to the placebo group than in women with intermediate or high risk, but this difference failed to reach statistical significance, Jane A. Cauley, Dr.P.H. said at the meeting.

The message is that postmenopausal women with osteoporosis should feel comfortable starting zoledronic acid treatment regardless of the severity of their fracture risk at baseline, said Dr. Cauley, professor of epidemiology at the University of Pittsburgh. It is not necessary to target treatment to women with an especially elevated fracture risk, such as those with a high FRAX (Fracture Risk Assessment Tool) score, she explained.

The results support a prior report with similar findings from the Women’s Health Initiative on the impact of estrogen or estrogen plus progesterone on fracture risk (JAMA 2003;290:1729-38). However, results from another prior study on the impact of clodronate on fracture risk suggested that osteoporotic women with the highest baseline fracture risk stood to gain the most from bisphosphonate treatment (Osteoporosis Int. 2009;20:811-17).

The current analysis used data collected in the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) pivotal fracture trial, which randomized 7,765 postmenopausal women to either an annual infusion with 5 mg zoledronic acid or placebo for 3 years (N. Engl. J. Me 2007;356:1809-22). Assessment of the study’s primary end point showed that annual treatment with zoledronic acid significantly cut the rate of vertebral and hip fractures as well as total clinical fractures.

To perform the post-hoc analysis, Dr. Cauley and her associates rated the baseline fracture risk of the 3,889 women randomized to receive zoledronic acid using a modification of the Fracture Index developed for the Study of Osteoporotic Fractures (SOF) (Osteoporosis Int. 2001;12:519-28). The modification calculated a woman’s baseline fracture risk using five of the seven variables of the SOF tool available in the HORIZON records: age, femoral neck bone mineral density T score, clinical fracture history, weight, and smoking status. The two SOF tool elements not available were maternal history of hip fracture and the use of arms to stand from a chair.

Analyses by Dr. Cauley and her associates using SOF data showed that calculating a fracture risk score with the five elements had a 98% correlation with the seven-item score, as well as a 64% correlation with women’s FRAX scores. To further confirm the validity of the modified SOF score, they calculated scores for the 3,876 women enrolled in the placebo arm of HORIZON. During 3 years of follow-up, the rate of total fractures per 1,000 person-years was 30, 35, and 45 respectively in the low-, intermediate-, and high-risk tertiles. Overall, for every 1-point rise in the modified SOF score, the risk of a fracture among the placebo women during follow-up rose by 11%, a statistically significant difference.

The researchers then assessed follow-up fracture rates among the low-, intermediate-, and high-risk women who received zoledronic acid. The rate of morphometric vertebral fractures compared with the placebo group fell by 80% in the low-risk tertile of women, by 69% in the intermediate-risk tertile, and by 68% in the high-risk women, differences that were not statistically significant.

The rate of all clinical fractures dropped by 35% in the low-risk women, 38% in the intermediate-risk women, and 30% in the high-risk women, also nonsignificant differences.

The rate of hip fractures with zoledronic acid treatment compared with placebo fell by 71% in the low-risk women, 41% in intermediate-risk women, and 22% in high-risk women. These between-group differences just missed being statistically significant (P = .06).

Additional analyses also showed that the zoledronic acid treatment consistently increased bone mineral density, and reduced two biomarkers of osteoporosis, procollagen type I N-propeptide and C-telopeptide cross-linked collagen, compared with the placebo group, regardless of baseline fracture risk, Dr. Cauley said.

HORIZON was supported by Novartis, the company that markets zoledronic acid (Reclast). Dr. Cauley said that she has received research funding from and has served as a consultant to Novartis.

TORONTO – Among postmenopausal women with osteoporosis, treatment with zoledronic acid had a similar effect on fracture reduction regardless of whether women had a low, intermediate, or high baseline fracture risk, based on a post-hoc analysis of nearly 3,900 women who received the agent in the drug’s pivotal trial for fracture prevention.

The analysis showed that rates of vertebral fractures and total clinical fractures fell by roughly similar amounts, regardless of the women’s baseline fracture risk, with annual injection of zoledronic acid during 3 years of treatment and follow-up.

The rate of hip fractures showed a greater reduction in women who entered the study in the lowest tertile for fracture risk relative to the placebo group than in women with intermediate or high risk, but this difference failed to reach statistical significance, Jane A. Cauley, Dr.P.H. said at the meeting.

The message is that postmenopausal women with osteoporosis should feel comfortable starting zoledronic acid treatment regardless of the severity of their fracture risk at baseline, said Dr. Cauley, professor of epidemiology at the University of Pittsburgh. It is not necessary to target treatment to women with an especially elevated fracture risk, such as those with a high FRAX (Fracture Risk Assessment Tool) score, she explained.

The results support a prior report with similar findings from the Women’s Health Initiative on the impact of estrogen or estrogen plus progesterone on fracture risk (JAMA 2003;290:1729-38). However, results from another prior study on the impact of clodronate on fracture risk suggested that osteoporotic women with the highest baseline fracture risk stood to gain the most from bisphosphonate treatment (Osteoporosis Int. 2009;20:811-17).

The current analysis used data collected in the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) pivotal fracture trial, which randomized 7,765 postmenopausal women to either an annual infusion with 5 mg zoledronic acid or placebo for 3 years (N. Engl. J. Me 2007;356:1809-22). Assessment of the study’s primary end point showed that annual treatment with zoledronic acid significantly cut the rate of vertebral and hip fractures as well as total clinical fractures.

To perform the post-hoc analysis, Dr. Cauley and her associates rated the baseline fracture risk of the 3,889 women randomized to receive zoledronic acid using a modification of the Fracture Index developed for the Study of Osteoporotic Fractures (SOF) (Osteoporosis Int. 2001;12:519-28). The modification calculated a woman’s baseline fracture risk using five of the seven variables of the SOF tool available in the HORIZON records: age, femoral neck bone mineral density T score, clinical fracture history, weight, and smoking status. The two SOF tool elements not available were maternal history of hip fracture and the use of arms to stand from a chair.

Analyses by Dr. Cauley and her associates using SOF data showed that calculating a fracture risk score with the five elements had a 98% correlation with the seven-item score, as well as a 64% correlation with women’s FRAX scores. To further confirm the validity of the modified SOF score, they calculated scores for the 3,876 women enrolled in the placebo arm of HORIZON. During 3 years of follow-up, the rate of total fractures per 1,000 person-years was 30, 35, and 45 respectively in the low-, intermediate-, and high-risk tertiles. Overall, for every 1-point rise in the modified SOF score, the risk of a fracture among the placebo women during follow-up rose by 11%, a statistically significant difference.

The researchers then assessed follow-up fracture rates among the low-, intermediate-, and high-risk women who received zoledronic acid. The rate of morphometric vertebral fractures compared with the placebo group fell by 80% in the low-risk tertile of women, by 69% in the intermediate-risk tertile, and by 68% in the high-risk women, differences that were not statistically significant.

The rate of all clinical fractures dropped by 35% in the low-risk women, 38% in the intermediate-risk women, and 30% in the high-risk women, also nonsignificant differences.

The rate of hip fractures with zoledronic acid treatment compared with placebo fell by 71% in the low-risk women, 41% in intermediate-risk women, and 22% in high-risk women. These between-group differences just missed being statistically significant (P = .06).

Additional analyses also showed that the zoledronic acid treatment consistently increased bone mineral density, and reduced two biomarkers of osteoporosis, procollagen type I N-propeptide and C-telopeptide cross-linked collagen, compared with the placebo group, regardless of baseline fracture risk, Dr. Cauley said.

HORIZON was supported by Novartis, the company that markets zoledronic acid (Reclast). Dr. Cauley said that she has received research funding from and has served as a consultant to Novartis.

TORONTO – Among postmenopausal women with osteoporosis, treatment with zoledronic acid had a similar effect on fracture reduction regardless of whether women had a low, intermediate, or high baseline fracture risk, based on a post-hoc analysis of nearly 3,900 women who received the agent in the drug’s pivotal trial for fracture prevention.

The analysis showed that rates of vertebral fractures and total clinical fractures fell by roughly similar amounts, regardless of the women’s baseline fracture risk, with annual injection of zoledronic acid during 3 years of treatment and follow-up.

The rate of hip fractures showed a greater reduction in women who entered the study in the lowest tertile for fracture risk relative to the placebo group than in women with intermediate or high risk, but this difference failed to reach statistical significance, Jane A. Cauley, Dr.P.H. said at the meeting.

The message is that postmenopausal women with osteoporosis should feel comfortable starting zoledronic acid treatment regardless of the severity of their fracture risk at baseline, said Dr. Cauley, professor of epidemiology at the University of Pittsburgh. It is not necessary to target treatment to women with an especially elevated fracture risk, such as those with a high FRAX (Fracture Risk Assessment Tool) score, she explained.

The results support a prior report with similar findings from the Women’s Health Initiative on the impact of estrogen or estrogen plus progesterone on fracture risk (JAMA 2003;290:1729-38). However, results from another prior study on the impact of clodronate on fracture risk suggested that osteoporotic women with the highest baseline fracture risk stood to gain the most from bisphosphonate treatment (Osteoporosis Int. 2009;20:811-17).

The current analysis used data collected in the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) pivotal fracture trial, which randomized 7,765 postmenopausal women to either an annual infusion with 5 mg zoledronic acid or placebo for 3 years (N. Engl. J. Med 2007;356:1809-22). Assessment of the study’s primary end point showed that annual treatment with zoledronic acid significantly cut the rate of vertebral and hip fractures as well as total clinical fractures.

To perform the post-hoc analysis, Dr. Cauley and her associates rated the baseline fracture risk of the 3,889 women randomized to receive zoledronic acid using a modification of the Fracture Index developed for the Study of Osteoporotic Fractures (SOF) (Osteoporosis Int. 2001;12:519-28). The modification calculated a woman’s baseline fracture risk using five of the seven variables of the SOF tool available in the HORIZON records: age, femoral neck bone mineral density T score, clinical fracture history, weight, and smoking status. The two SOF tool elements not available were maternal history of hip fracture and the use of arms to stand from a chair.

Analyses by Dr. Cauley and her associates using SOF data showed that calculating a fracture risk score with the five elements had a 98% correlation with the seven-item score, as well as a 64% correlation with women’s FRAX scores. To further confirm the validity of the modified SOF score, they calculated scores for the 3,876 women enrolled in the placebo arm of HORIZON. During 3 years of follow-up, the rate of total fractures per 1,000 person-years was 30, 35, and 45 respectively in the low-, intermediate-, and high-risk tertiles. Overall, for every 1-point rise in the modified SOF score, the risk of a fracture among the placebo women during follow-up rose by 11%, a statistically significant difference.

The researchers then assessed follow-up fracture rates among the low-, intermediate-, and high-risk women who received zoledronic acid. The rate of morphometric vertebral fractures compared with the placebo group fell by 80% in the low-risk tertile of women, by 69% in the intermediate-risk tertile, and by 68% in the high-risk women, differences that were not statistically significant.

The rate of all clinical fractures dropped by 35% in the low-risk women, 38% in the intermediate-risk women, and 30% in the high-risk women, also nonsignificant differences.

The rate of hip fractures with zoledronic acid treatment compared with placebo fell by 71% in the low-risk women, 41% in intermediate-risk women, and 22% in high-risk women. These between-group differences just missed being statistically significant (P = .06).

Additional analyses also showed that the zoledronic acid treatment consistently increased bone mineral density, and reduced two biomarkers of osteoporosis, procollagen type I N-propeptide and C-telopeptide cross-linked collagen, compared with the placebo group, regardless of baseline fracture risk, Dr. Cauley said.

HORIZON was supported by Novartis, the company that markets zoledronic acid (Reclast). Dr. Cauley said that she has received research funding from and has served as a consultant to Novartis.

TORONTO – Among postmenopausal women with osteoporosis, treatment with zoledronic acid had a similar effect on fracture reduction regardless of whether women had a low, intermediate, or high baseline fracture risk, based on a post-hoc analysis of nearly 3,900 women who received the agent in the drug’s pivotal trial for fracture prevention.

The analysis showed that rates of vertebral fractures and total clinical fractures fell by roughly similar amounts, regardless of the women’s baseline fracture risk, with annual injection of zoledronic acid during 3 years of treatment and follow-up.

The rate of hip fractures showed a greater reduction in women who entered the study in the lowest tertile for fracture risk relative to the placebo group than in women with intermediate or high risk, but this difference failed to reach statistical significance, Jane A. Cauley, Dr.P.H. said at the meeting.

The message is that postmenopausal women with osteoporosis should feel comfortable starting zoledronic acid treatment regardless of the severity of their fracture risk at baseline, said Dr. Cauley, professor of epidemiology at the University of Pittsburgh. It is not necessary to target treatment to women with an especially elevated fracture risk, such as those with a high FRAX (Fracture Risk Assessment Tool) score, she explained.

The results support a prior report with similar findings from the Women’s Health Initiative on the impact of estrogen or estrogen plus progesterone on fracture risk (JAMA 2003;290:1729-38). However, results from another prior study on the impact of clodronate on fracture risk suggested that osteoporotic women with the highest baseline fracture risk stood to gain the most from bisphosphonate treatment (Osteoporosis Int. 2009;20:811-17).

The current analysis used data collected in the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) pivotal fracture trial, which randomized 7,765 postmenopausal women to either an annual infusion with 5 mg zoledronic acid or placebo for 3 years (N. Engl. J. Med 2007;356:1809-22). Assessment of the study’s primary end point showed that annual treatment with zoledronic acid significantly cut the rate of vertebral and hip fractures as well as total clinical fractures.

To perform the post-hoc analysis, Dr. Cauley and her associates rated the baseline fracture risk of the 3,889 women randomized to receive zoledronic acid using a modification of the Fracture Index developed for the Study of Osteoporotic Fractures (SOF) (Osteoporosis Int. 2001;12:519-28). The modification calculated a woman’s baseline fracture risk using five of the seven variables of the SOF tool available in the HORIZON records: age, femoral neck bone mineral density T score, clinical fracture history, weight, and smoking status. The two SOF tool elements not available were maternal history of hip fracture and the use of arms to stand from a chair.

Analyses by Dr. Cauley and her associates using SOF data showed that calculating a fracture risk score with the five elements had a 98% correlation with the seven-item score, as well as a 64% correlation with women’s FRAX scores. To further confirm the validity of the modified SOF score, they calculated scores for the 3,876 women enrolled in the placebo arm of HORIZON. During 3 years of follow-up, the rate of total fractures per 1,000 person-years was 30, 35, and 45 respectively in the low-, intermediate-, and high-risk tertiles. Overall, for every 1-point rise in the modified SOF score, the risk of a fracture among the placebo women during follow-up rose by 11%, a statistically significant difference.

The researchers then assessed follow-up fracture rates among the low-, intermediate-, and high-risk women who received zoledronic acid. The rate of morphometric vertebral fractures compared with the placebo group fell by 80% in the low-risk tertile of women, by 69% in the intermediate-risk tertile, and by 68% in the high-risk women, differences that were not statistically significant.

The rate of all clinical fractures dropped by 35% in the low-risk women, 38% in the intermediate-risk women, and 30% in the high-risk women, also nonsignificant differences.

The rate of hip fractures with zoledronic acid treatment compared with placebo fell by 71% in the low-risk women, 41% in intermediate-risk women, and 22% in high-risk women. These between-group differences just missed being statistically significant (P = .06).

Additional analyses also showed that the zoledronic acid treatment consistently increased bone mineral density, and reduced two biomarkers of osteoporosis, procollagen type I N-propeptide and C-telopeptide cross-linked collagen, compared with the placebo group, regardless of baseline fracture risk, Dr. Cauley said.

HORIZON was supported by Novartis, the company that markets zoledronic acid (Reclast). Dr. Cauley said that she has received research funding from and has served as a consultant to Novartis.

TORONTO – Among postmenopausal women with osteoporosis, treatment with zoledronic acid had a similar effect on fracture reduction regardless of whether women had a low, intermediate, or high baseline fracture risk, based on a post-hoc analysis of nearly 3,900 women who received the agent in the drug’s pivotal trial for fracture prevention.

The analysis showed that rates of vertebral fractures and total clinical fractures fell by roughly similar amounts, regardless of the women’s baseline fracture risk, with annual injection of zoledronic acid during 3 years of treatment and follow-up.

The rate of hip fractures showed a greater reduction in women who entered the study in the lowest tertile for fracture risk relative to the placebo group than in women with intermediate or high risk, but this difference failed to reach statistical significance, Jane A. Cauley, Dr.P.H. said at the meeting.

The message is that postmenopausal women with osteoporosis should feel comfortable starting zoledronic acid treatment regardless of the severity of their fracture risk at baseline, said Dr. Cauley, professor of epidemiology at the University of Pittsburgh. It is not necessary to target treatment to women with an especially elevated fracture risk, such as those with a high FRAX (Fracture Risk Assessment Tool) score, she explained.

The results support a prior report with similar findings from the Women’s Health Initiative on the impact of estrogen or estrogen plus progesterone on fracture risk (JAMA 2003;290:1729-38). However, results from another prior study on the impact of clodronate on fracture risk suggested that osteoporotic women with the highest baseline fracture risk stood to gain the most from bisphosphonate treatment (Osteoporosis Int. 2009;20:811-17).

The current analysis used data collected in the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) pivotal fracture trial, which randomized 7,765 postmenopausal women to either an annual infusion with 5 mg zoledronic acid or placebo for 3 years (N. Engl. J. Med 2007;356:1809-22). Assessment of the study’s primary end point showed that annual treatment with zoledronic acid significantly cut the rate of vertebral and hip fractures as well as total clinical fractures.

To perform the post-hoc analysis, Dr. Cauley and her associates rated the baseline fracture risk of the 3,889 women randomized to receive zoledronic acid using a modification of the Fracture Index developed for the Study of Osteoporotic Fractures (SOF) (Osteoporosis Int. 2001;12:519-28). The modification calculated a woman’s baseline fracture risk using five of the seven variables of the SOF tool available in the HORIZON records: age, femoral neck bone mineral density T score, clinical fracture history, weight, and smoking status. The two SOF tool elements not available were maternal history of hip fracture and the use of arms to stand from a chair.

Analyses by Dr. Cauley and her associates using SOF data showed that calculating a fracture risk score with the five elements had a 98% correlation with the seven-item score, as well as a 64% correlation with women’s FRAX scores. To further confirm the validity of the modified SOF score, they calculated scores for the 3,876 women enrolled in the placebo arm of HORIZON. During 3 years of follow-up, the rate of total fractures per 1,000 person-years was 30, 35, and 45 respectively in the low-, intermediate-, and high-risk tertiles. Overall, for every 1-point rise in the modified SOF score, the risk of a fracture among the placebo women during follow-up rose by 11%, a statistically significant difference.

The researchers then assessed follow-up fracture rates among the low-, intermediate-, and high-risk women who received zoledronic acid. The rate of morphometric vertebral fractures compared with the placebo group fell by 80% in the low-risk tertile of women, by 69% in the intermediate-risk tertile, and by 68% in the high-risk women, differences that were not statistically significant.

The rate of all clinical fractures dropped by 35% in the low-risk women, 38% in the intermediate-risk women, and 30% in the high-risk women, also nonsignificant differences.

The rate of hip fractures with zoledronic acid treatment compared with placebo fell by 71% in the low-risk women, 41% in intermediate-risk women, and 22% in high-risk women. These between-group differences just missed being statistically significant (P = .06).

Additional analyses also showed that the zoledronic acid treatment consistently increased bone mineral density, and reduced two biomarkers of osteoporosis, procollagen type I N-propeptide and C-telopeptide cross-linked collagen, compared with the placebo group, regardless of baseline fracture risk, Dr. Cauley said.

HORIZON was supported by Novartis, the company that markets zoledronic acid (Reclast). Dr. Cauley said that she has received research funding from and has served as a consultant to Novartis.

CHICAGO – Closure-device problems did not explain why endovascular closure of patent foramen ovale in patients with a history of cryptogenic stroke failed to produce better outcomes than those of medically-treated patients. The device performed well, Dr. Anthony J. Furlan said at the annual scientific sessions of the American Heart Association.

The problem was patient selection.

"For the vast majority of patients who have had a cryptogenic stroke and a patent foramen ovale [PFO] medical therapy is a good first-choice," said Dr. Furlan, professor and chairman of neurology at Case Western Reserve University in Cleveland. "The challenge now to the endovascular community is to refine the patient selection criteria and not close these holes so liberally."

Based on the results from A Prospective, Multicenter, Randomized Controlled Trial to Evaluate the Safety and Efficacy of the STARFlex Septal Closure System Versus Best Medical Therapy in Patients With a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale (CLOSURE I), the first randomized study to compare anticoagulant therapy and endovascular PFO closure, "we should see a significant drop in the number of PFOs that get closed," Dr. Furlan said.

The CLOSURE I investigators selected patients "who are being closed worldwide," he said. "Many patients who have a cryptogenic stroke also have a hole and nothing else, but people don’t look that hard. Assessments tend to stop when they find a PFO, he said.

The CLOSURE I results "clearly showed that in patients with stroke of unknown cause and PFO there is no need for systematic PFO closure because it is not effective and may be associated with major vascular complications, atrial fibrillation, or bleeding," said Dr. Pierre Amarenco, professor and chairman of the department of neurology and stroke center at Bichat Hospital in Paris. "Cryptogenic stroke likely includes a broad range of underlying etiologies that may have diluted the true, causal effect of PFO. These results should now be translated into practice for the million patients with stroke of unknown cause and PFO. On a case-by-case basis, after careful evaluation by a vascular neurologist, there may be some patients for whom closing the PFO can be deemed useful, but these cases are likely very rare."

CLOSURE I enrolled 18- to 60-year-olds who had a cryptogenic stroke or transient ischemic attack (TIA) within the past 6 months, and a PFO documented by transesophageal echocardiography. Investigators at 87 centers in the United States and Canada randomized 909 patients during June 2003–October 2008 to endovascular closure with the STARFlex device or to medical therapy. Patients in the closure group also received aspirin and clopidogrel for 6 months following their procedure, followed by aspirin alone for an additional 18 months. Patients in the medical-treatment arm received warfarin alone, dosed to a target international normalized ratio of 2.0-3.0 (139 patients), warfarin plus aspirin (80 patients), or aspirin alone (243 patients) throughout their follow-up. The average age of the patients was 46; 52% were men. Nearly three-quarters had an index cryptogenic stroke.

"We believe the study population was representative of patients aged 60 or younger with cryptogenic stroke or TIA and a PFO," Dr. Furlan said.

The study’s primary end points were the individual rates of stroke and TIA and the composite rate after 2 years of follow-up on an intent-to-treat basis. The composite rates were 5.9% among the 447 patients in the closure group and 7.7% among 462 patients in the medical-therapy group, a difference that was not statistically significant. The numeric difference was driven primarily by a difference in the TIA rate, 3.3% in the closure group and 4.6% in the medical therapy group, not significantly different. The stroke rates were nearly identical in the two groups, 3.1% and 3.4%. The composite end point showed no significant difference between the two treatment arms regardless of the shunt severity or whether or not the patients had an atrial septal aneurysm.

Roughly 80% of the strokes that occurred during follow-up in both arms of the study had no relationship to paradoxical embolism, suggesting that in many of these patients the PFO may be coincidental, Dr. Furlan said.

In the control arm, the outcomes did not significantly differ regardless of whether patients received warfarin plus aspirin, warfarin alone, or aspirin alone. Dr. Furlan noted that the study was not powered to find significant differences among these three subgroups.

The overall rate of major adverse events was similar, 17%, in both treatment arms (see table). Patients who underwent PFO closure had significantly more major vascular complications and atrial fibrillations. Vascular complications occurred completely secondary to the closures, with none in the medically-managed patients, Dr. Furlan said. The closure procedure achieved technical success in 90% of patients in that arm of the study, with 86% of the PFOs closed at 6 months after treatment based on follow-up echocardiography examinations.

The CLOSURE I study was sponsored by NMT Medical, which markets the STARFlex closure device. Dr. Furlan said that he is a consultant to NMT Medical and was the principal investigator for the trial. Dr. Amarenco said that he has received research grants from Sanofi-Aventis, Bristol-Myers Squibb, AstraZeneca, Merck, and Pfizer.

CHICAGO – Closure-device problems did not explain why endovascular closure of patent foramen ovale in patients with a history of cryptogenic stroke failed to produce better outcomes than those of medically-treated patients. The device performed well, Dr. Anthony J. Furlan said at the annual scientific sessions of the American Heart Association.

The problem was patient selection.

"For the vast majority of patients who have had a cryptogenic stroke and a patent foramen ovale [PFO] medical therapy is a good first-choice," said Dr. Furlan, professor and chairman of neurology at Case Western Reserve University in Cleveland. "The challenge now to the endovascular community is to refine the patient selection criteria and not close these holes so liberally."

Based on the results from A Prospective, Multicenter, Randomized Controlled Trial to Evaluate the Safety and Efficacy of the STARFlex Septal Closure System Versus Best Medical Therapy in Patients With a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale (CLOSURE I), the first randomized study to compare anticoagulant therapy and endovascular PFO closure, "we should see a significant drop in the number of PFOs that get closed," Dr. Furlan said.

The CLOSURE I investigators selected patients "who are being closed worldwide," he said. "Many patients who have a cryptogenic stroke also have a hole and nothing else, but people don’t look that hard. Assessments tend to stop when they find a PFO, he said.

The CLOSURE I results "clearly showed that in patients with stroke of unknown cause and PFO there is no need for systematic PFO closure because it is not effective and may be associated with major vascular complications, atrial fibrillation, or bleeding," said Dr. Pierre Amarenco, professor and chairman of the department of neurology and stroke center at Bichat Hospital in Paris. "Cryptogenic stroke likely includes a broad range of underlying etiologies that may have diluted the true, causal effect of PFO. These results should now be translated into practice for the million patients with stroke of unknown cause and PFO. On a case-by-case basis, after careful evaluation by a vascular neurologist, there may be some patients for whom closing the PFO can be deemed useful, but these cases are likely very rare."

CLOSURE I enrolled 18- to 60-year-olds who had a cryptogenic stroke or transient ischemic attack (TIA) within the past 6 months, and a PFO documented by transesophageal echocardiography. Investigators at 87 centers in the United States and Canada randomized 909 patients during June 2003–October 2008 to endovascular closure with the STARFlex device or to medical therapy. Patients in the closure group also received aspirin and clopidogrel for 6 months following their procedure, followed by aspirin alone for an additional 18 months. Patients in the medical-treatment arm received warfarin alone, dosed to a target international normalized ratio of 2.0-3.0 (139 patients), warfarin plus aspirin (80 patients), or aspirin alone (243 patients) throughout their follow-up. The average age of the patients was 46; 52% were men. Nearly three-quarters had an index cryptogenic stroke.

"We believe the study population was representative of patients aged 60 or younger with cryptogenic stroke or TIA and a PFO," Dr. Furlan said.

The study’s primary end points were the individual rates of stroke and TIA and the composite rate after 2 years of follow-up on an intent-to-treat basis. The composite rates were 5.9% among the 447 patients in the closure group and 7.7% among 462 patients in the medical-therapy group, a difference that was not statistically significant. The numeric difference was driven primarily by a difference in the TIA rate, 3.3% in the closure group and 4.6% in the medical therapy group, not significantly different. The stroke rates were nearly identical in the two groups, 3.1% and 3.4%. The composite end point showed no significant difference between the two treatment arms regardless of the shunt severity or whether or not the patients had an atrial septal aneurysm.

Roughly 80% of the strokes that occurred during follow-up in both arms of the study had no relationship to paradoxical embolism, suggesting that in many of these patients the PFO may be coincidental, Dr. Furlan said.

In the control arm, the outcomes did not significantly differ regardless of whether patients received warfarin plus aspirin, warfarin alone, or aspirin alone. Dr. Furlan noted that the study was not powered to find significant differences among these three subgroups.

The overall rate of major adverse events was similar, 17%, in both treatment arms (see table). Patients who underwent PFO closure had significantly more major vascular complications and atrial fibrillations. Vascular complications occurred completely secondary to the closures, with none in the medically-managed patients, Dr. Furlan said. The closure procedure achieved technical success in 90% of patients in that arm of the study, with 86% of the PFOs closed at 6 months after treatment based on follow-up echocardiography examinations.

The CLOSURE I study was sponsored by NMT Medical, which markets the STARFlex closure device. Dr. Furlan said that he is a consultant to NMT Medical and was the principal investigator for the trial. Dr. Amarenco said that he has received research grants from Sanofi-Aventis, Bristol-Myers Squibb, AstraZeneca, Merck, and Pfizer.

CHICAGO – Closure-device problems did not explain why endovascular closure of patent foramen ovale in patients with a history of cryptogenic stroke failed to produce better outcomes than those of medically-treated patients. The device performed well, Dr. Anthony J. Furlan said at the annual scientific sessions of the American Heart Association.

The problem was patient selection.

"For the vast majority of patients who have had a cryptogenic stroke and a patent foramen ovale [PFO] medical therapy is a good first-choice," said Dr. Furlan, professor and chairman of neurology at Case Western Reserve University in Cleveland. "The challenge now to the endovascular community is to refine the patient selection criteria and not close these holes so liberally."

Based on the results from A Prospective, Multicenter, Randomized Controlled Trial to Evaluate the Safety and Efficacy of the STARFlex Septal Closure System Versus Best Medical Therapy in Patients With a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale (CLOSURE I), the first randomized study to compare anticoagulant therapy and endovascular PFO closure, "we should see a significant drop in the number of PFOs that get closed," Dr. Furlan said.

The CLOSURE I investigators selected patients "who are being closed worldwide," he said. "Many patients who have a cryptogenic stroke also have a hole and nothing else, but people don’t look that hard. Assessments tend to stop when they find a PFO, he said.

The CLOSURE I results "clearly showed that in patients with stroke of unknown cause and PFO there is no need for systematic PFO closure because it is not effective and may be associated with major vascular complications, atrial fibrillation, or bleeding," said Dr. Pierre Amarenco, professor and chairman of the department of neurology and stroke center at Bichat Hospital in Paris. "Cryptogenic stroke likely includes a broad range of underlying etiologies that may have diluted the true, causal effect of PFO. These results should now be translated into practice for the million patients with stroke of unknown cause and PFO. On a case-by-case basis, after careful evaluation by a vascular neurologist, there may be some patients for whom closing the PFO can be deemed useful, but these cases are likely very rare."

CLOSURE I enrolled 18- to 60-year-olds who had a cryptogenic stroke or transient ischemic attack (TIA) within the past 6 months, and a PFO documented by transesophageal echocardiography. Investigators at 87 centers in the United States and Canada randomized 909 patients during June 2003–October 2008 to endovascular closure with the STARFlex device or to medical therapy. Patients in the closure group also received aspirin and clopidogrel for 6 months following their procedure, followed by aspirin alone for an additional 18 months. Patients in the medical-treatment arm received warfarin alone, dosed to a target international normalized ratio of 2.0-3.0 (139 patients), warfarin plus aspirin (80 patients), or aspirin alone (243 patients) throughout their follow-up. The average age of the patients was 46; 52% were men. Nearly three-quarters had an index cryptogenic stroke.

"We believe the study population was representative of patients aged 60 or younger with cryptogenic stroke or TIA and a PFO," Dr. Furlan said.

The study’s primary end points were the individual rates of stroke and TIA and the composite rate after 2 years of follow-up on an intent-to-treat basis. The composite rates were 5.9% among the 447 patients in the closure group and 7.7% among 462 patients in the medical-therapy group, a difference that was not statistically significant. The numeric difference was driven primarily by a difference in the TIA rate, 3.3% in the closure group and 4.6% in the medical therapy group, not significantly different. The stroke rates were nearly identical in the two groups, 3.1% and 3.4%. The composite end point showed no significant difference between the two treatment arms regardless of the shunt severity or whether or not the patients had an atrial septal aneurysm.

Roughly 80% of the strokes that occurred during follow-up in both arms of the study had no relationship to paradoxical embolism, suggesting that in many of these patients the PFO may be coincidental, Dr. Furlan said.

In the control arm, the outcomes did not significantly differ regardless of whether patients received warfarin plus aspirin, warfarin alone, or aspirin alone. Dr. Furlan noted that the study was not powered to find significant differences among these three subgroups.

The overall rate of major adverse events was similar, 17%, in both treatment arms (see table). Patients who underwent PFO closure had significantly more major vascular complications and atrial fibrillations. Vascular complications occurred completely secondary to the closures, with none in the medically-managed patients, Dr. Furlan said. The closure procedure achieved technical success in 90% of patients in that arm of the study, with 86% of the PFOs closed at 6 months after treatment based on follow-up echocardiography examinations.

The CLOSURE I study was sponsored by NMT Medical, which markets the STARFlex closure device. Dr. Furlan said that he is a consultant to NMT Medical and was the principal investigator for the trial. Dr. Amarenco said that he has received research grants from Sanofi-Aventis, Bristol-Myers Squibb, AstraZeneca, Merck, and Pfizer.

Major Finding: In women who received zoledronic acid, the rate of all clinical fractures dropped by 35% in the low-risk women, 38% in the intermediate-risk women, and 30% in the high-risk women.

Data Source: Post-hoc analysis of 3,889 women who received zoledronic acid in the HORIZON pivotal fracture study that compared zoledronic acid infusions against placebo.

Disclosures: HORIZON was supported by Novartis, the company that markets zoledronic acid. Dr. Cauley said that she has received research funding from and has served as a consultant to Novartis.

TORONTO – Among postmenopausal women with osteoporosis, treatment with zoledronic acid had a similar effect on fracture reduction regardless of whether women had a low, intermediate, or high baseline fracture risk, based on a post-hoc analysis of nearly 3,900 women who received the agent in the drug's pivotal trial for fracture prevention.

The analysis showed that rates of vertebral fractures and total clinical fractures fell by roughly similar amounts, regardless of the women's baseline fracture risk, with annual injection of zoledronic acid during 3 years of treatment and follow-up.

The rate of hip fractures showed a greater reduction in women who entered the study in the lowest tertile for fracture risk relative to the placebo group than in women with intermediate or high risk, but this difference failed to reach statistical significance, Jane A. Cauley, Dr.P.H. said at the meeting.

The message is that postmenopausal women with osteoporosis should feel comfortable starting zoledronic acid treatment regardless of the severity of their fracture risk at baseline, said Dr. Cauley, professor of epidemiology at the University of Pittsburgh. It is not necessary to target treatment to women with an especially elevated fracture risk, such as those with a high FRAX (Fracture Risk Assessment Tool) score, she explained.

The results support a prior report with similar findings from the Women's Health Initiative on the impact of estrogen or estrogen plus progesterone on fracture risk (JAMA 2003;290:1729-38). However, results from another prior study on the impact of clodronate on fracture risk suggested that osteoporotic women with the highest baseline fracture risk stood to gain the most from bisphosphonate treatment (Osteoporosis Int. 2009;20:811-17).

The current analysis used data collected in the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) pivotal fracture trial, which randomized 7,765 postmenopausal women to either an annual infusion with 5 mg zoledronic acid or placebo for 3 years (N. Engl. J. Med 2007;356:1809-22).

Assessment of the study's primary end point showed that annual treatment with zoledronic acid significantly cut the rate of vertebral and hip fractures as well as total clinical fractures.

To perform the post-hoc analysis, Dr. Cauley and her associates rated the baseline fracture risk of the 3,889 women randomized to receive zoledronic acid using a modification of the Fracture Index developed for the Study of Osteoporotic Fractures (SOF) (Osteoporosis Int. 2001;12:519-28).

The modification calculated a woman's baseline fracture risk using five of the seven variables of the SOF tool available in the HORIZON records: age, femoral neck bone mineral density T score, clinical fracture history, weight, and smoking status. The two SOF tool elements not available were maternal history of hip fracture and the use of arms to stand from a chair.

Analyses by Dr. Cauley and her associates using SOF data showed that calculating a fracture risk score with the five elements had a 98% correlation with the seven-item score, as well as a 64% correlation with women's FRAX scores. To further confirm the validity of the modified SOF score, they calculated scores for the 3,876 women enrolled in the placebo arm of HORIZON. During 3 years of follow-up, the rate of total fractures per 1,000 person-years was 30, 35, and 45 respectively in the low-, intermediate-, and high-risk tertiles. Overall, for every 1-point rise in the modified SOF score, the risk of a fracture among the placebo women during follow-up rose by 11%, a statistically significant difference.

The researchers then assessed follow-up fracture rates among the low-, intermediate-, and high-risk women who received zoledronic acid. The rate of morphometric vertebral fractures compared with the placebo group fell by 80% in the low-risk tertile of women, by 69% in the intermediate-risk tertile, and by 68% in the high-risk women, differences that were not statistically significant.

The rate of all clinical fractures dropped by 35% in the low-risk women, 38% in the intermediate-risk women, and 30% in the high-risk women, also nonsignificant differences.

The rate of hip fractures with zoledronic acid treatment compared with placebo fell by 71% in the low-risk women, 41% in intermediate-risk women, and 22% in high-risk women. These between-group differences just missed being statistically significant.

Additional analyses also showed that the zoledronic acid treatment consistently increased bone mineral density, and reduced two biomarkers of osteoporosis, procollagen type I N-propeptide and C-telopeptide cross-linked collagen, compared with the placebo group, regardless of baseline fracture risk, Dr. Cauley said.

It is not necessary to target treatment to women with an especially elevated fracture risk.

Source DR. CAULEY

Major Finding: In women who received zoledronic acid, the rate of all clinical fractures dropped by 35% in the low-risk women, 38% in the intermediate-risk women, and 30% in the high-risk women.

Data Source: Post-hoc analysis of 3,889 women who received zoledronic acid in the HORIZON pivotal fracture study that compared zoledronic acid infusions against placebo.

Disclosures: HORIZON was supported by Novartis, the company that markets zoledronic acid. Dr. Cauley said that she has received research funding from and has served as a consultant to Novartis.

TORONTO – Among postmenopausal women with osteoporosis, treatment with zoledronic acid had a similar effect on fracture reduction regardless of whether women had a low, intermediate, or high baseline fracture risk, based on a post-hoc analysis of nearly 3,900 women who received the agent in the drug's pivotal trial for fracture prevention.

The analysis showed that rates of vertebral fractures and total clinical fractures fell by roughly similar amounts, regardless of the women's baseline fracture risk, with annual injection of zoledronic acid during 3 years of treatment and follow-up.

The rate of hip fractures showed a greater reduction in women who entered the study in the lowest tertile for fracture risk relative to the placebo group than in women with intermediate or high risk, but this difference failed to reach statistical significance, Jane A. Cauley, Dr.P.H. said at the meeting.

The message is that postmenopausal women with osteoporosis should feel comfortable starting zoledronic acid treatment regardless of the severity of their fracture risk at baseline, said Dr. Cauley, professor of epidemiology at the University of Pittsburgh. It is not necessary to target treatment to women with an especially elevated fracture risk, such as those with a high FRAX (Fracture Risk Assessment Tool) score, she explained.

The results support a prior report with similar findings from the Women's Health Initiative on the impact of estrogen or estrogen plus progesterone on fracture risk (JAMA 2003;290:1729-38). However, results from another prior study on the impact of clodronate on fracture risk suggested that osteoporotic women with the highest baseline fracture risk stood to gain the most from bisphosphonate treatment (Osteoporosis Int. 2009;20:811-17).

The current analysis used data collected in the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) pivotal fracture trial, which randomized 7,765 postmenopausal women to either an annual infusion with 5 mg zoledronic acid or placebo for 3 years (N. Engl. J. Med 2007;356:1809-22).

Assessment of the study's primary end point showed that annual treatment with zoledronic acid significantly cut the rate of vertebral and hip fractures as well as total clinical fractures.

To perform the post-hoc analysis, Dr. Cauley and her associates rated the baseline fracture risk of the 3,889 women randomized to receive zoledronic acid using a modification of the Fracture Index developed for the Study of Osteoporotic Fractures (SOF) (Osteoporosis Int. 2001;12:519-28).

The modification calculated a woman's baseline fracture risk using five of the seven variables of the SOF tool available in the HORIZON records: age, femoral neck bone mineral density T score, clinical fracture history, weight, and smoking status. The two SOF tool elements not available were maternal history of hip fracture and the use of arms to stand from a chair.

Analyses by Dr. Cauley and her associates using SOF data showed that calculating a fracture risk score with the five elements had a 98% correlation with the seven-item score, as well as a 64% correlation with women's FRAX scores. To further confirm the validity of the modified SOF score, they calculated scores for the 3,876 women enrolled in the placebo arm of HORIZON. During 3 years of follow-up, the rate of total fractures per 1,000 person-years was 30, 35, and 45 respectively in the low-, intermediate-, and high-risk tertiles. Overall, for every 1-point rise in the modified SOF score, the risk of a fracture among the placebo women during follow-up rose by 11%, a statistically significant difference.

The researchers then assessed follow-up fracture rates among the low-, intermediate-, and high-risk women who received zoledronic acid. The rate of morphometric vertebral fractures compared with the placebo group fell by 80% in the low-risk tertile of women, by 69% in the intermediate-risk tertile, and by 68% in the high-risk women, differences that were not statistically significant.

The rate of all clinical fractures dropped by 35% in the low-risk women, 38% in the intermediate-risk women, and 30% in the high-risk women, also nonsignificant differences.

The rate of hip fractures with zoledronic acid treatment compared with placebo fell by 71% in the low-risk women, 41% in intermediate-risk women, and 22% in high-risk women. These between-group differences just missed being statistically significant.

Additional analyses also showed that the zoledronic acid treatment consistently increased bone mineral density, and reduced two biomarkers of osteoporosis, procollagen type I N-propeptide and C-telopeptide cross-linked collagen, compared with the placebo group, regardless of baseline fracture risk, Dr. Cauley said.

It is not necessary to target treatment to women with an especially elevated fracture risk.

Source DR. CAULEY

Major Finding: In women who received zoledronic acid, the rate of all clinical fractures dropped by 35% in the low-risk women, 38% in the intermediate-risk women, and 30% in the high-risk women.

Data Source: Post-hoc analysis of 3,889 women who received zoledronic acid in the HORIZON pivotal fracture study that compared zoledronic acid infusions against placebo.

Disclosures: HORIZON was supported by Novartis, the company that markets zoledronic acid. Dr. Cauley said that she has received research funding from and has served as a consultant to Novartis.

TORONTO – Among postmenopausal women with osteoporosis, treatment with zoledronic acid had a similar effect on fracture reduction regardless of whether women had a low, intermediate, or high baseline fracture risk, based on a post-hoc analysis of nearly 3,900 women who received the agent in the drug's pivotal trial for fracture prevention.

The analysis showed that rates of vertebral fractures and total clinical fractures fell by roughly similar amounts, regardless of the women's baseline fracture risk, with annual injection of zoledronic acid during 3 years of treatment and follow-up.

The rate of hip fractures showed a greater reduction in women who entered the study in the lowest tertile for fracture risk relative to the placebo group than in women with intermediate or high risk, but this difference failed to reach statistical significance, Jane A. Cauley, Dr.P.H. said at the meeting.

The message is that postmenopausal women with osteoporosis should feel comfortable starting zoledronic acid treatment regardless of the severity of their fracture risk at baseline, said Dr. Cauley, professor of epidemiology at the University of Pittsburgh. It is not necessary to target treatment to women with an especially elevated fracture risk, such as those with a high FRAX (Fracture Risk Assessment Tool) score, she explained.

The results support a prior report with similar findings from the Women's Health Initiative on the impact of estrogen or estrogen plus progesterone on fracture risk (JAMA 2003;290:1729-38). However, results from another prior study on the impact of clodronate on fracture risk suggested that osteoporotic women with the highest baseline fracture risk stood to gain the most from bisphosphonate treatment (Osteoporosis Int. 2009;20:811-17).

The current analysis used data collected in the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) pivotal fracture trial, which randomized 7,765 postmenopausal women to either an annual infusion with 5 mg zoledronic acid or placebo for 3 years (N. Engl. J. Med 2007;356:1809-22).

Assessment of the study's primary end point showed that annual treatment with zoledronic acid significantly cut the rate of vertebral and hip fractures as well as total clinical fractures.

To perform the post-hoc analysis, Dr. Cauley and her associates rated the baseline fracture risk of the 3,889 women randomized to receive zoledronic acid using a modification of the Fracture Index developed for the Study of Osteoporotic Fractures (SOF) (Osteoporosis Int. 2001;12:519-28).

The modification calculated a woman's baseline fracture risk using five of the seven variables of the SOF tool available in the HORIZON records: age, femoral neck bone mineral density T score, clinical fracture history, weight, and smoking status. The two SOF tool elements not available were maternal history of hip fracture and the use of arms to stand from a chair.

Analyses by Dr. Cauley and her associates using SOF data showed that calculating a fracture risk score with the five elements had a 98% correlation with the seven-item score, as well as a 64% correlation with women's FRAX scores. To further confirm the validity of the modified SOF score, they calculated scores for the 3,876 women enrolled in the placebo arm of HORIZON. During 3 years of follow-up, the rate of total fractures per 1,000 person-years was 30, 35, and 45 respectively in the low-, intermediate-, and high-risk tertiles. Overall, for every 1-point rise in the modified SOF score, the risk of a fracture among the placebo women during follow-up rose by 11%, a statistically significant difference.

The researchers then assessed follow-up fracture rates among the low-, intermediate-, and high-risk women who received zoledronic acid. The rate of morphometric vertebral fractures compared with the placebo group fell by 80% in the low-risk tertile of women, by 69% in the intermediate-risk tertile, and by 68% in the high-risk women, differences that were not statistically significant.

The rate of all clinical fractures dropped by 35% in the low-risk women, 38% in the intermediate-risk women, and 30% in the high-risk women, also nonsignificant differences.

The rate of hip fractures with zoledronic acid treatment compared with placebo fell by 71% in the low-risk women, 41% in intermediate-risk women, and 22% in high-risk women. These between-group differences just missed being statistically significant.

Additional analyses also showed that the zoledronic acid treatment consistently increased bone mineral density, and reduced two biomarkers of osteoporosis, procollagen type I N-propeptide and C-telopeptide cross-linked collagen, compared with the placebo group, regardless of baseline fracture risk, Dr. Cauley said.

It is not necessary to target treatment to women with an especially elevated fracture risk.

Source DR. CAULEY

Major Finding: The rate of atypical femur fractures in patients with osteoporosis who were treated with a bisphosphonate rose with increased duration of use. On average, 50 atypical fractures occurred for every 100,000 patients treated for 5 years, 100 atypical fractures occurred per 100,000 patients treated for 6 years, and almost 250 atypical fractures occurred per 100,000 patients treated for 12 years.

Data Source: Review of radiographs from 1,448 Kaiser California patients with a diaphyseal femur fracture during January 2007 through December 2009, including 135 that met the atypical criteria.

Disclosures: Dr. Ott and Dr. Wang had no disclosures. Dr. Shane has been a consultant to Amgen and has received research support from Merck, Novartis, and Eli Lilly.

TORONTO – Patients with osteoporosis who are on bisphosphonate therapy clearly face an increased treatment-linked risk for atypical femur fractures, but at a low rate that is dwarfed by the number of typical hip fractures the drugs prevent.

The risk for atypical fracture appears to rise substantially as time on the drug increases, but an atypical fracture can occur at any time, prompting experts to stress that a bisphosphonate should be given only to a patient who needs the treatment. And the prodromal thigh or groin pain that precedes a majority of atypical fractures should alert physicians to stop bisphosphonate treatment, although stopping the drug is no guarantee against a subsequent atypical fracture.

Above all, experts agreed, atypical fracture risk is no reason to deny bisphosphonate treatment to patients who need it, because these drugs improve bone mineral density and prevent typical hip fractures, and because in appropriate patients this benefit far exceeds the atypical fracture risk.

This consensus on how to view bisphosphonates and their risk for causing atypical fractures pervaded the meeting One multispeaker session during the meeting reviewed the data compiled by and the recommendations from an American Society for Bone and Mineral Research (ASBMR) task force that were published online late last year, while several other speakers reported some of the incidence data that task force members considered when writing their recommendations (J. Bone Miner. Res. 2010 [doi:10.1002/jbmr.253]).

“The message is that for patients with osteoporosis at high risk of having a fracture, treatment with a bisphosphonate will benefit far more than risk for an atypical fracture,” said Dr. Elizabeth Shane, a professor of medicine at Columbia University in New York, and cochair of the task force. h

The largest and most comprehensive look at atypical fracture rates came from data compiled from the 2.6 million beneficiaries older than 45 years enrolled in Kaiser California. During January 2007 through December 2009, 15,819 people had femur fractures, excluding those from major trauma, those secondary to Paget's disease or metastatic lesions, or periprosthetic fractures. The researchers reviewed the radiographs for 1,448 of these fractures located in the diaphyseal region.

Of the reviewed fractures, the researchers identified 135 as atypical, based on their location in the diaphyseal portion of the femur, either in the shaft or subtrochanteric region, as well as other features: a transverse fracture, usually with lateral cortical thickening especially at the fracture site, and flaring of the lateral cortex, Dr. Susan Ott of the University of Washington, Seattle, reported at the meeting.

The 135 patients with atypical fractures were 98% women, with an average age of 71 years and an average body mass index of 26.6 kg/m

All but 4% of the atypical fracture patients received a bisphosphonate at the time of fracture, and were on their regimen for an average of 6 years. Two-thirds had prodromal thigh pain, and 26% had bilateral atypical fractures. In all, 60% of the fractures occurred in the femur shaft, and 40% were in the subtrochanteric region.

The most common age at fracture was 65–69 years, with a majority of atypical fracture patients aged 65 or older. The fracture rate rose steadily with increasing years of bisphosphonate use, with most fractures occurring in patients who had used the drugs for at least 5 years, even though these long-term users represented a small minority of all Kaiser patients who used a bisphosphonate during the 3 years studied. The number of fractures per 100,000 people exposed rose steadily with increasing years of use, reaching 50 per 100,000 when bisphosphonate use continued for 5 years and 100 fractures per 100,000 patients in those using the drug for 6 years, and then continuing to rise steadily with added years of use, reaching a high of nearly 250 fractures for every 100,000 patients exposed to a bisphosphonate for 12 years.

“These data do not suggest you should stop using bisphosphonates, especially in women with osteoporosis. Bisphosphonates look pretty safe for the first few years,” Dr. Ott said. But, she added, “the data argue that if a patient does not have osteoporosis, then bisphosphonates are not the appropriate drug.”

The ASBMR task force reviewed Dr. Ott's data before issuing its recommendations in October 2010. The data “were very informative for establishing incidence rates for these fractures,” Dr. Shane said in an interview.

Another talk at the meeting presented additional data documenting the relative risks of atypical and typical fractures with bisphosphonate treatment.

Patients taking a bisphosphonate face a risk of about 1 additional subtrochanteric hip fracture for every 100 typical hip fractures prevented, according to an analysis of national data during 1996–2007.

The new data present no direct evidence for a role of bisphosphonate use in causing subtrochanteric hip fractures, which along with femoral shaft fractures constitute the “atypical” category. But the temporal link between the steady increase in bisphosphonate use among elderly American women during 1996–2007 and the concurrent rise in subtrochanteric fractures also in elderly American women strongly suggests that a causal link exists, John Wang, Ph.D., a statistician at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, said.

He analyzed data on U.S. subtrochanteric fracture rates from the Nationwide Inpatient Sample during 1996–2007, along with data on U.S. bisphosphonate use from the Medical Expenditure Panel Survey. The analysis showed that the start of widespread bisphosphonate use in 1996, quickly followed by even broader use over the following years, had a temporal relationship with subtrochanteric fractures, which began rising in 2000.

Recommended Steps to Reduce Risk

Despite substantial evidence linking long-term bisphosphonate use and an increased rate of atypical femur fractures, bisphosphonates remain an effective and attractive drug class for treating osteoporosis, experts said at the meeting.

The task force assembled by the ASBMR recommended several steps for physicians to take when they prescribe a bisphosphonate to reduce the atypical fracture risk faced by patients.

Patients with a low absolute fracture risk should not receive a bisphosphonate, said Dr. Peter R. Ebeling, a task force member, summarizing the group's recommendations at the ASBMR's annual meeting.

Another step is minimizing the duration of bisphosphonate treatment. This means realizing that patients with secondary causes of rapid bone loss may not need long-term bisphosphonate treatment. Continued use of the drugs beyond 5 years should be evaluated annually, said Dr. Ebeling, professor and chairman of medicine at the University of Melbourne.

Patients without a recent fracture and with a femoral neck T score of more than −2.5 after 5 years of continuous bisphosphonate treatment should receive consideration for a drug holiday. Patients who are taken off bisphosphonate treatment should undergo an annual assessment of their clinical status, markers of bone turnover, bone density, and fracture risk.

Because a majority of patients who developed an atypical fracture on bisphosphonate treatment had prodromal pain in their thigh or groin, physicians should alert patients to watch for and promptly report such pain. During regular examinations of patients on a bisphosphonate or another potent antiresorptive drug, physicians should ask if prodromal pain exists. When suspicious pain occurs, the patient needs “urgent” radiographic assessment of both femora, even for unilateral pain, Dr. Ebeling said. If the radiographs appear normal, perform a follow-up examination by MRI or radionuclide scintigraphy scanning. Physicians should be aware that bilateral, atypical femur fractures can occur; patients with an atypical fracture of one femur face a fracture risk in their contralateral femur.

If a patient has a fracture while on a bisphosphonate, treatment with the bisphosphonate or any other potent antiresorptive drug should stop. At that time, assess the patient's calcium and vitamin D status and prescribe adequate supplementation if needed. The physician should consider prescribing teriparatide to improve fracture healing, particularly if it appears that the fracture has not healed by 4–6 weeks following surgical repair. In patients who should not receive teriparatide, such as those with a history of breast cancer or skeletal irradiation, consider another option such as treatment with raloxifene.

When an atypical fracture occurs, the physician “should look at the other leg. It's an opportunity to prevent more fractures by paying attention to a patient's symptoms and acting on them,” said Dr. Elizabeth Shane. Reduced weight bearing can reduce fracture risk in patients who develop prodromal pain or a unilateral, atypical fracture, she said in an interview. Another option is prophylactic rod placement on their intact femur to reduce future fracture risk.

Dr. Ebeling said that he has served as a speaker for Merck, Eli Lilly, Novartis, and Sanofi-Aventis; that he has been on advisory boards for Merck, Amgen, and Novartis; has received educational grants from Amgen, Eli Lilly, and Sanofi-Aventis; and has received research grants from Merck, Novartis, and Amgen.

Major Finding: The rate of atypical femur fractures in patients with osteoporosis who were treated with a bisphosphonate rose with increased duration of use. On average, 50 atypical fractures occurred for every 100,000 patients treated for 5 years, 100 atypical fractures occurred per 100,000 patients treated for 6 years, and almost 250 atypical fractures occurred per 100,000 patients treated for 12 years.

Data Source: Review of radiographs from 1,448 Kaiser California patients with a diaphyseal femur fracture during January 2007 through December 2009, including 135 that met the atypical criteria.

Disclosures: Dr. Ott and Dr. Wang had no disclosures. Dr. Shane has been a consultant to Amgen and has received research support from Merck, Novartis, and Eli Lilly.

TORONTO – Patients with osteoporosis who are on bisphosphonate therapy clearly face an increased treatment-linked risk for atypical femur fractures, but at a low rate that is dwarfed by the number of typical hip fractures the drugs prevent.

The risk for atypical fracture appears to rise substantially as time on the drug increases, but an atypical fracture can occur at any time, prompting experts to stress that a bisphosphonate should be given only to a patient who needs the treatment. And the prodromal thigh or groin pain that precedes a majority of atypical fractures should alert physicians to stop bisphosphonate treatment, although stopping the drug is no guarantee against a subsequent atypical fracture.

Above all, experts agreed, atypical fracture risk is no reason to deny bisphosphonate treatment to patients who need it, because these drugs improve bone mineral density and prevent typical hip fractures, and because in appropriate patients this benefit far exceeds the atypical fracture risk.

This consensus on how to view bisphosphonates and their risk for causing atypical fractures pervaded the meeting One multispeaker session during the meeting reviewed the data compiled by and the recommendations from an American Society for Bone and Mineral Research (ASBMR) task force that were published online late last year, while several other speakers reported some of the incidence data that task force members considered when writing their recommendations (J. Bone Miner. Res. 2010 [doi:10.1002/jbmr.253]).

“The message is that for patients with osteoporosis at high risk of having a fracture, treatment with a bisphosphonate will benefit far more than risk for an atypical fracture,” said Dr. Elizabeth Shane, a professor of medicine at Columbia University in New York, and cochair of the task force. h

The largest and most comprehensive look at atypical fracture rates came from data compiled from the 2.6 million beneficiaries older than 45 years enrolled in Kaiser California. During January 2007 through December 2009, 15,819 people had femur fractures, excluding those from major trauma, those secondary to Paget's disease or metastatic lesions, or periprosthetic fractures. The researchers reviewed the radiographs for 1,448 of these fractures located in the diaphyseal region.

Of the reviewed fractures, the researchers identified 135 as atypical, based on their location in the diaphyseal portion of the femur, either in the shaft or subtrochanteric region, as well as other features: a transverse fracture, usually with lateral cortical thickening especially at the fracture site, and flaring of the lateral cortex, Dr. Susan Ott of the University of Washington, Seattle, reported at the meeting.

The 135 patients with atypical fractures were 98% women, with an average age of 71 years and an average body mass index of 26.6 kg/m

All but 4% of the atypical fracture patients received a bisphosphonate at the time of fracture, and were on their regimen for an average of 6 years. Two-thirds had prodromal thigh pain, and 26% had bilateral atypical fractures. In all, 60% of the fractures occurred in the femur shaft, and 40% were in the subtrochanteric region.

The most common age at fracture was 65–69 years, with a majority of atypical fracture patients aged 65 or older. The fracture rate rose steadily with increasing years of bisphosphonate use, with most fractures occurring in patients who had used the drugs for at least 5 years, even though these long-term users represented a small minority of all Kaiser patients who used a bisphosphonate during the 3 years studied. The number of fractures per 100,000 people exposed rose steadily with increasing years of use, reaching 50 per 100,000 when bisphosphonate use continued for 5 years and 100 fractures per 100,000 patients in those using the drug for 6 years, and then continuing to rise steadily with added years of use, reaching a high of nearly 250 fractures for every 100,000 patients exposed to a bisphosphonate for 12 years.

“These data do not suggest you should stop using bisphosphonates, especially in women with osteoporosis. Bisphosphonates look pretty safe for the first few years,” Dr. Ott said. But, she added, “the data argue that if a patient does not have osteoporosis, then bisphosphonates are not the appropriate drug.”

The ASBMR task force reviewed Dr. Ott's data before issuing its recommendations in October 2010. The data “were very informative for establishing incidence rates for these fractures,” Dr. Shane said in an interview.

Another talk at the meeting presented additional data documenting the relative risks of atypical and typical fractures with bisphosphonate treatment.

Patients taking a bisphosphonate face a risk of about 1 additional subtrochanteric hip fracture for every 100 typical hip fractures prevented, according to an analysis of national data during 1996–2007.

The new data present no direct evidence for a role of bisphosphonate use in causing subtrochanteric hip fractures, which along with femoral shaft fractures constitute the “atypical” category. But the temporal link between the steady increase in bisphosphonate use among elderly American women during 1996–2007 and the concurrent rise in subtrochanteric fractures also in elderly American women strongly suggests that a causal link exists, John Wang, Ph.D., a statistician at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, said.

He analyzed data on U.S. subtrochanteric fracture rates from the Nationwide Inpatient Sample during 1996–2007, along with data on U.S. bisphosphonate use from the Medical Expenditure Panel Survey. The analysis showed that the start of widespread bisphosphonate use in 1996, quickly followed by even broader use over the following years, had a temporal relationship with subtrochanteric fractures, which began rising in 2000.

Recommended Steps to Reduce Risk

Despite substantial evidence linking long-term bisphosphonate use and an increased rate of atypical femur fractures, bisphosphonates remain an effective and attractive drug class for treating osteoporosis, experts said at the meeting.

The task force assembled by the ASBMR recommended several steps for physicians to take when they prescribe a bisphosphonate to reduce the atypical fracture risk faced by patients.

Patients with a low absolute fracture risk should not receive a bisphosphonate, said Dr. Peter R. Ebeling, a task force member, summarizing the group's recommendations at the ASBMR's annual meeting.

Another step is minimizing the duration of bisphosphonate treatment. This means realizing that patients with secondary causes of rapid bone loss may not need long-term bisphosphonate treatment. Continued use of the drugs beyond 5 years should be evaluated annually, said Dr. Ebeling, professor and chairman of medicine at the University of Melbourne.

Patients without a recent fracture and with a femoral neck T score of more than −2.5 after 5 years of continuous bisphosphonate treatment should receive consideration for a drug holiday. Patients who are taken off bisphosphonate treatment should undergo an annual assessment of their clinical status, markers of bone turnover, bone density, and fracture risk.

Because a majority of patients who developed an atypical fracture on bisphosphonate treatment had prodromal pain in their thigh or groin, physicians should alert patients to watch for and promptly report such pain. During regular examinations of patients on a bisphosphonate or another potent antiresorptive drug, physicians should ask if prodromal pain exists. When suspicious pain occurs, the patient needs “urgent” radiographic assessment of both femora, even for unilateral pain, Dr. Ebeling said. If the radiographs appear normal, perform a follow-up examination by MRI or radionuclide scintigraphy scanning. Physicians should be aware that bilateral, atypical femur fractures can occur; patients with an atypical fracture of one femur face a fracture risk in their contralateral femur.

If a patient has a fracture while on a bisphosphonate, treatment with the bisphosphonate or any other potent antiresorptive drug should stop. At that time, assess the patient's calcium and vitamin D status and prescribe adequate supplementation if needed. The physician should consider prescribing teriparatide to improve fracture healing, particularly if it appears that the fracture has not healed by 4–6 weeks following surgical repair. In patients who should not receive teriparatide, such as those with a history of breast cancer or skeletal irradiation, consider another option such as treatment with raloxifene.

When an atypical fracture occurs, the physician “should look at the other leg. It's an opportunity to prevent more fractures by paying attention to a patient's symptoms and acting on them,” said Dr. Elizabeth Shane. Reduced weight bearing can reduce fracture risk in patients who develop prodromal pain or a unilateral, atypical fracture, she said in an interview. Another option is prophylactic rod placement on their intact femur to reduce future fracture risk.

Dr. Ebeling said that he has served as a speaker for Merck, Eli Lilly, Novartis, and Sanofi-Aventis; that he has been on advisory boards for Merck, Amgen, and Novartis; has received educational grants from Amgen, Eli Lilly, and Sanofi-Aventis; and has received research grants from Merck, Novartis, and Amgen.

Major Finding: The rate of atypical femur fractures in patients with osteoporosis who were treated with a bisphosphonate rose with increased duration of use. On average, 50 atypical fractures occurred for every 100,000 patients treated for 5 years, 100 atypical fractures occurred per 100,000 patients treated for 6 years, and almost 250 atypical fractures occurred per 100,000 patients treated for 12 years.

Data Source: Review of radiographs from 1,448 Kaiser California patients with a diaphyseal femur fracture during January 2007 through December 2009, including 135 that met the atypical criteria.

Disclosures: Dr. Ott and Dr. Wang had no disclosures. Dr. Shane has been a consultant to Amgen and has received research support from Merck, Novartis, and Eli Lilly.

TORONTO – Patients with osteoporosis who are on bisphosphonate therapy clearly face an increased treatment-linked risk for atypical femur fractures, but at a low rate that is dwarfed by the number of typical hip fractures the drugs prevent.

The risk for atypical fracture appears to rise substantially as time on the drug increases, but an atypical fracture can occur at any time, prompting experts to stress that a bisphosphonate should be given only to a patient who needs the treatment. And the prodromal thigh or groin pain that precedes a majority of atypical fractures should alert physicians to stop bisphosphonate treatment, although stopping the drug is no guarantee against a subsequent atypical fracture.

Above all, experts agreed, atypical fracture risk is no reason to deny bisphosphonate treatment to patients who need it, because these drugs improve bone mineral density and prevent typical hip fractures, and because in appropriate patients this benefit far exceeds the atypical fracture risk.

This consensus on how to view bisphosphonates and their risk for causing atypical fractures pervaded the meeting One multispeaker session during the meeting reviewed the data compiled by and the recommendations from an American Society for Bone and Mineral Research (ASBMR) task force that were published online late last year, while several other speakers reported some of the incidence data that task force members considered when writing their recommendations (J. Bone Miner. Res. 2010 [doi:10.1002/jbmr.253]).

“The message is that for patients with osteoporosis at high risk of having a fracture, treatment with a bisphosphonate will benefit far more than risk for an atypical fracture,” said Dr. Elizabeth Shane, a professor of medicine at Columbia University in New York, and cochair of the task force. h

The largest and most comprehensive look at atypical fracture rates came from data compiled from the 2.6 million beneficiaries older than 45 years enrolled in Kaiser California. During January 2007 through December 2009, 15,819 people had femur fractures, excluding those from major trauma, those secondary to Paget's disease or metastatic lesions, or periprosthetic fractures. The researchers reviewed the radiographs for 1,448 of these fractures located in the diaphyseal region.

Of the reviewed fractures, the researchers identified 135 as atypical, based on their location in the diaphyseal portion of the femur, either in the shaft or subtrochanteric region, as well as other features: a transverse fracture, usually with lateral cortical thickening especially at the fracture site, and flaring of the lateral cortex, Dr. Susan Ott of the University of Washington, Seattle, reported at the meeting.

The 135 patients with atypical fractures were 98% women, with an average age of 71 years and an average body mass index of 26.6 kg/m

All but 4% of the atypical fracture patients received a bisphosphonate at the time of fracture, and were on their regimen for an average of 6 years. Two-thirds had prodromal thigh pain, and 26% had bilateral atypical fractures. In all, 60% of the fractures occurred in the femur shaft, and 40% were in the subtrochanteric region.

The most common age at fracture was 65–69 years, with a majority of atypical fracture patients aged 65 or older. The fracture rate rose steadily with increasing years of bisphosphonate use, with most fractures occurring in patients who had used the drugs for at least 5 years, even though these long-term users represented a small minority of all Kaiser patients who used a bisphosphonate during the 3 years studied. The number of fractures per 100,000 people exposed rose steadily with increasing years of use, reaching 50 per 100,000 when bisphosphonate use continued for 5 years and 100 fractures per 100,000 patients in those using the drug for 6 years, and then continuing to rise steadily with added years of use, reaching a high of nearly 250 fractures for every 100,000 patients exposed to a bisphosphonate for 12 years.

“These data do not suggest you should stop using bisphosphonates, especially in women with osteoporosis. Bisphosphonates look pretty safe for the first few years,” Dr. Ott said. But, she added, “the data argue that if a patient does not have osteoporosis, then bisphosphonates are not the appropriate drug.”

The ASBMR task force reviewed Dr. Ott's data before issuing its recommendations in October 2010. The data “were very informative for establishing incidence rates for these fractures,” Dr. Shane said in an interview.

Another talk at the meeting presented additional data documenting the relative risks of atypical and typical fractures with bisphosphonate treatment.

Patients taking a bisphosphonate face a risk of about 1 additional subtrochanteric hip fracture for every 100 typical hip fractures prevented, according to an analysis of national data during 1996–2007.

The new data present no direct evidence for a role of bisphosphonate use in causing subtrochanteric hip fractures, which along with femoral shaft fractures constitute the “atypical” category. But the temporal link between the steady increase in bisphosphonate use among elderly American women during 1996–2007 and the concurrent rise in subtrochanteric fractures also in elderly American women strongly suggests that a causal link exists, John Wang, Ph.D., a statistician at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, said.

He analyzed data on U.S. subtrochanteric fracture rates from the Nationwide Inpatient Sample during 1996–2007, along with data on U.S. bisphosphonate use from the Medical Expenditure Panel Survey. The analysis showed that the start of widespread bisphosphonate use in 1996, quickly followed by even broader use over the following years, had a temporal relationship with subtrochanteric fractures, which began rising in 2000.

Recommended Steps to Reduce Risk

Despite substantial evidence linking long-term bisphosphonate use and an increased rate of atypical femur fractures, bisphosphonates remain an effective and attractive drug class for treating osteoporosis, experts said at the meeting.

The task force assembled by the ASBMR recommended several steps for physicians to take when they prescribe a bisphosphonate to reduce the atypical fracture risk faced by patients.

Patients with a low absolute fracture risk should not receive a bisphosphonate, said Dr. Peter R. Ebeling, a task force member, summarizing the group's recommendations at the ASBMR's annual meeting.

Another step is minimizing the duration of bisphosphonate treatment. This means realizing that patients with secondary causes of rapid bone loss may not need long-term bisphosphonate treatment. Continued use of the drugs beyond 5 years should be evaluated annually, said Dr. Ebeling, professor and chairman of medicine at the University of Melbourne.

Patients without a recent fracture and with a femoral neck T score of more than −2.5 after 5 years of continuous bisphosphonate treatment should receive consideration for a drug holiday. Patients who are taken off bisphosphonate treatment should undergo an annual assessment of their clinical status, markers of bone turnover, bone density, and fracture risk.

Because a majority of patients who developed an atypical fracture on bisphosphonate treatment had prodromal pain in their thigh or groin, physicians should alert patients to watch for and promptly report such pain. During regular examinations of patients on a bisphosphonate or another potent antiresorptive drug, physicians should ask if prodromal pain exists. When suspicious pain occurs, the patient needs “urgent” radiographic assessment of both femora, even for unilateral pain, Dr. Ebeling said. If the radiographs appear normal, perform a follow-up examination by MRI or radionuclide scintigraphy scanning. Physicians should be aware that bilateral, atypical femur fractures can occur; patients with an atypical fracture of one femur face a fracture risk in their contralateral femur.

If a patient has a fracture while on a bisphosphonate, treatment with the bisphosphonate or any other potent antiresorptive drug should stop. At that time, assess the patient's calcium and vitamin D status and prescribe adequate supplementation if needed. The physician should consider prescribing teriparatide to improve fracture healing, particularly if it appears that the fracture has not healed by 4–6 weeks following surgical repair. In patients who should not receive teriparatide, such as those with a history of breast cancer or skeletal irradiation, consider another option such as treatment with raloxifene.

When an atypical fracture occurs, the physician “should look at the other leg. It's an opportunity to prevent more fractures by paying attention to a patient's symptoms and acting on them,” said Dr. Elizabeth Shane. Reduced weight bearing can reduce fracture risk in patients who develop prodromal pain or a unilateral, atypical fracture, she said in an interview. Another option is prophylactic rod placement on their intact femur to reduce future fracture risk.

Dr. Ebeling said that he has served as a speaker for Merck, Eli Lilly, Novartis, and Sanofi-Aventis; that he has been on advisory boards for Merck, Amgen, and Novartis; has received educational grants from Amgen, Eli Lilly, and Sanofi-Aventis; and has received research grants from Merck, Novartis, and Amgen.

TORONTO – Among postmenopausal women with osteoporosis, treatment with zoledronic acid had a similar effect on fracture reduction regardless of whether women had a low, intermediate, or high baseline fracture risk, based on a post-hoc analysis of nearly 3,900 women who received the agent in the drug's pivotal trial for fracture prevention.

The analysis showed that rates of vertebral fractures and total clinical fractures fell by roughly similar amounts, regardless of the women's baseline fracture risk, with annual injection of zoledronic acid during 3 years of treatment and follow-up.

The rate of hip fractures showed a greater reduction in women who entered the study in the lowest tertile for fracture risk relative to the placebo group than in women with intermediate or high risk, but this difference failed to reach statistical significance, Jane A. Cauley, Dr.P.H. said at the meeting.

The message is that postmenopausal women with osteoporosis should feel comfortable starting zoledronic acid treatment regardless of the severity of their fracture risk at baseline, said Dr. Cauley, professor of epidemiology at the University of Pittsburgh.

It is not necessary to target treatment to women with an especially elevated fracture risk, such as those with a high FRAX (Fracture Risk Assessment Tool) score, she explained.

The current analysis used data collected in the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) pivotal fracture trial, which randomized 7,765 postmenopausal women to either an annual infusion with 5 mg zoledronic acid or placebo for 3 years (N. Engl. J. Med 2007;356:1809-22).

Assessment of the study's primary end point showed that annual treatment with zoledronic acid significantly cut the rate of vertebral and hip fractures as well as total clinical fractures.

To perform the post-hoc analysis, Dr. Cauley and her associates rated the baseline fracture risk of the 3,889 women randomized to receive zole-dronic acid using a modification of the Fracture Index developed for the Study of Osteoporotic Fractures (SOF) (Osteoporosis Int. 2001;12:519-28).

The modification calculated a woman's baseline fracture risk using five of the seven variables of the SOF tool available in the HORIZON records: age, femoral neck bone mineral density T score, clinical fracture history, weight, and smoking status. The two SOF tool elements not available were maternal history of hip fracture and the use of arms to stand from a chair.

Analyses by Dr. Cauley and her associates using SOF data showed that calculating a fracture risk score with the five elements had a 98% correlation with the seven-item score, as well as a 64% correlation with women's FRAX scores. To further confirm the validity of the modified SOF score, they calculated scores for the 3,876 women enrolled in the placebo arm of HORIZON.

During 3 years of follow-up, the rate of total fractures per 1,000 person-years was 30, 35, and 45, respectively, in the low-, intermediate-, and high-risk tertiles.

Overall, for every 1-point rise in the modified SOF score, the risk of a fracture among the placebo women during follow-up rose by 11%, a statistically significant difference.

HORIZON was supported by Novartis, the company that markets zoledronic acid. Dr. Cauley said that she has received research funding from and has served as a consultant to Novartis.

TORONTO – Among postmenopausal women with osteoporosis, treatment with zoledronic acid had a similar effect on fracture reduction regardless of whether women had a low, intermediate, or high baseline fracture risk, based on a post-hoc analysis of nearly 3,900 women who received the agent in the drug's pivotal trial for fracture prevention.

The analysis showed that rates of vertebral fractures and total clinical fractures fell by roughly similar amounts, regardless of the women's baseline fracture risk, with annual injection of zoledronic acid during 3 years of treatment and follow-up.

The rate of hip fractures showed a greater reduction in women who entered the study in the lowest tertile for fracture risk relative to the placebo group than in women with intermediate or high risk, but this difference failed to reach statistical significance, Jane A. Cauley, Dr.P.H. said at the meeting.

The message is that postmenopausal women with osteoporosis should feel comfortable starting zoledronic acid treatment regardless of the severity of their fracture risk at baseline, said Dr. Cauley, professor of epidemiology at the University of Pittsburgh.

It is not necessary to target treatment to women with an especially elevated fracture risk, such as those with a high FRAX (Fracture Risk Assessment Tool) score, she explained.

The current analysis used data collected in the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) pivotal fracture trial, which randomized 7,765 postmenopausal women to either an annual infusion with 5 mg zoledronic acid or placebo for 3 years (N. Engl. J. Med 2007;356:1809-22).

Assessment of the study's primary end point showed that annual treatment with zoledronic acid significantly cut the rate of vertebral and hip fractures as well as total clinical fractures.

To perform the post-hoc analysis, Dr. Cauley and her associates rated the baseline fracture risk of the 3,889 women randomized to receive zole-dronic acid using a modification of the Fracture Index developed for the Study of Osteoporotic Fractures (SOF) (Osteoporosis Int. 2001;12:519-28).

The modification calculated a woman's baseline fracture risk using five of the seven variables of the SOF tool available in the HORIZON records: age, femoral neck bone mineral density T score, clinical fracture history, weight, and smoking status. The two SOF tool elements not available were maternal history of hip fracture and the use of arms to stand from a chair.

Analyses by Dr. Cauley and her associates using SOF data showed that calculating a fracture risk score with the five elements had a 98% correlation with the seven-item score, as well as a 64% correlation with women's FRAX scores. To further confirm the validity of the modified SOF score, they calculated scores for the 3,876 women enrolled in the placebo arm of HORIZON.

During 3 years of follow-up, the rate of total fractures per 1,000 person-years was 30, 35, and 45, respectively, in the low-, intermediate-, and high-risk tertiles.

Overall, for every 1-point rise in the modified SOF score, the risk of a fracture among the placebo women during follow-up rose by 11%, a statistically significant difference.

HORIZON was supported by Novartis, the company that markets zoledronic acid. Dr. Cauley said that she has received research funding from and has served as a consultant to Novartis.

TORONTO – Among postmenopausal women with osteoporosis, treatment with zoledronic acid had a similar effect on fracture reduction regardless of whether women had a low, intermediate, or high baseline fracture risk, based on a post-hoc analysis of nearly 3,900 women who received the agent in the drug's pivotal trial for fracture prevention.

The analysis showed that rates of vertebral fractures and total clinical fractures fell by roughly similar amounts, regardless of the women's baseline fracture risk, with annual injection of zoledronic acid during 3 years of treatment and follow-up.

The rate of hip fractures showed a greater reduction in women who entered the study in the lowest tertile for fracture risk relative to the placebo group than in women with intermediate or high risk, but this difference failed to reach statistical significance, Jane A. Cauley, Dr.P.H. said at the meeting.

The message is that postmenopausal women with osteoporosis should feel comfortable starting zoledronic acid treatment regardless of the severity of their fracture risk at baseline, said Dr. Cauley, professor of epidemiology at the University of Pittsburgh.

It is not necessary to target treatment to women with an especially elevated fracture risk, such as those with a high FRAX (Fracture Risk Assessment Tool) score, she explained.

The current analysis used data collected in the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) pivotal fracture trial, which randomized 7,765 postmenopausal women to either an annual infusion with 5 mg zoledronic acid or placebo for 3 years (N. Engl. J. Med 2007;356:1809-22).

Assessment of the study's primary end point showed that annual treatment with zoledronic acid significantly cut the rate of vertebral and hip fractures as well as total clinical fractures.

To perform the post-hoc analysis, Dr. Cauley and her associates rated the baseline fracture risk of the 3,889 women randomized to receive zole-dronic acid using a modification of the Fracture Index developed for the Study of Osteoporotic Fractures (SOF) (Osteoporosis Int. 2001;12:519-28).

The modification calculated a woman's baseline fracture risk using five of the seven variables of the SOF tool available in the HORIZON records: age, femoral neck bone mineral density T score, clinical fracture history, weight, and smoking status. The two SOF tool elements not available were maternal history of hip fracture and the use of arms to stand from a chair.

Analyses by Dr. Cauley and her associates using SOF data showed that calculating a fracture risk score with the five elements had a 98% correlation with the seven-item score, as well as a 64% correlation with women's FRAX scores. To further confirm the validity of the modified SOF score, they calculated scores for the 3,876 women enrolled in the placebo arm of HORIZON.

During 3 years of follow-up, the rate of total fractures per 1,000 person-years was 30, 35, and 45, respectively, in the low-, intermediate-, and high-risk tertiles.

Overall, for every 1-point rise in the modified SOF score, the risk of a fracture among the placebo women during follow-up rose by 11%, a statistically significant difference.

HORIZON was supported by Novartis, the company that markets zoledronic acid. Dr. Cauley said that she has received research funding from and has served as a consultant to Novartis.

Major Finding: A novel trifurcation technique safely preserved flow through the internal iliac arteries in patients who underwent an endovascular abdominal aortic aneurysm repair with an aneurysm in one or both common iliac arteries.

Data Source: A single-center series of 34 patients.

Disclosures: Dr. Lobato said that he had no disclosures.

MIAMI BEACH — A novel, trifurcated, endovascular stenting procedure allowed preservation of blood flow through the internal iliac artery of patients undergoing repair of a thoracoabdominal aortic aneurysm or an aortoiliac aneurysm.

Dr. Armando C. Lobato, who developed the technique, has successfully used it on 34 patients, including 7 patients who required bilateral repairs, he said at the meeting, sponsored by the Society of Interventional Radiology.

Dr. Lobato performed his first trifurcation procedure – which he also calls the Brazilian Sandwich procedure – in August 2008.

He reported having 100% technical success using the procedure, with no operative deaths and no need to convert to an open procedure.

During a median follow-up of 5 months (range, 2–24 months), no patient experienced colonic or buttock necrosis, no patient had ischemic colitis, and there were no type III endoleaks.

In all, 39 (95%) of the 41 treated internal iliac (hypogastric) arteries maintained primary patency. As a result of the procedure, occlusions also occurred in one contralateral iliac limb and in one ipsilateral external iliac artery. Secondary patency was maintained in 38 of the 41 treated arteries and their associated vessels, said Dr. Lobato, medical director of the Vascular and Endovascular Surgery Institute in São Paulo, Brazil.

About 20%–30% of patients with abdominal aortic aneurysm also have aneurysms in one or both of their common iliac arteries. Endovascular repair in these patients is harder because of the difficulty in finding an adequate landing zone for the stent-graft limbs and because the iliac aneurysm is a potential site for an endoleak.

In addition, some patients have short common iliac arteries, an anatomy that is especially prevalent in patients of Asian descent and on the right side of the body. Dr. Lobato said that he developed the trifurcation technique to overcome these anatomical problems so that endovascular aneurysm repair could expand in a safe and cost-effective way via a method that was easy to perform.

Dr. Lobato broke the trifurcation technique into the following five steps:

▸ First, he inserts the main, bifurcated stent graft using an ipsilateral femoral approach. He positions the graft so that the distal end of the iliac limb is 1 cm above the origin of the internal iliac artery.

▸ Second, he inserts a long, 5-Fr multipurpose catheter into the ipsilateral internal iliac artery using left brachial access and a 0.035-inch, extra-stiff guide wire with a floppy tip.

▸ In the third step, he places a covered, self-expanding stent 2 cm into the internal iliac artery with a 6-cm overlap into the iliac limb. He also then positions an iliac limb extension 1 cm below the proximal end of the covered stent. He deploys the iliac limb extension first, followed by deployment of the covered stent.

▸ Fourth, he models the iliac limb stents with a latex balloon and dilates the covered stent with an angioplasty balloon.

▸ For the final, fifth step, he deploys the graft within the contralateral iliac limb.

In patients with bilateral aneurysms in their common iliac artery, he repeats steps 2–4 on the second side.

In all, 39 (95%) of the 41 treated internal iliac arteries maintained primary patency.

Source DR. LOBATO

Major Finding: A novel trifurcation technique safely preserved flow through the internal iliac arteries in patients who underwent an endovascular abdominal aortic aneurysm repair with an aneurysm in one or both common iliac arteries.

Data Source: A single-center series of 34 patients.

Disclosures: Dr. Lobato said that he had no disclosures.

MIAMI BEACH — A novel, trifurcated, endovascular stenting procedure allowed preservation of blood flow through the internal iliac artery of patients undergoing repair of a thoracoabdominal aortic aneurysm or an aortoiliac aneurysm.

Dr. Armando C. Lobato, who developed the technique, has successfully used it on 34 patients, including 7 patients who required bilateral repairs, he said at the meeting, sponsored by the Society of Interventional Radiology.

Dr. Lobato performed his first trifurcation procedure – which he also calls the Brazilian Sandwich procedure – in August 2008.

He reported having 100% technical success using the procedure, with no operative deaths and no need to convert to an open procedure.

During a median follow-up of 5 months (range, 2–24 months), no patient experienced colonic or buttock necrosis, no patient had ischemic colitis, and there were no type III endoleaks.

In all, 39 (95%) of the 41 treated internal iliac (hypogastric) arteries maintained primary patency. As a result of the procedure, occlusions also occurred in one contralateral iliac limb and in one ipsilateral external iliac artery. Secondary patency was maintained in 38 of the 41 treated arteries and their associated vessels, said Dr. Lobato, medical director of the Vascular and Endovascular Surgery Institute in São Paulo, Brazil.

About 20%–30% of patients with abdominal aortic aneurysm also have aneurysms in one or both of their common iliac arteries. Endovascular repair in these patients is harder because of the difficulty in finding an adequate landing zone for the stent-graft limbs and because the iliac aneurysm is a potential site for an endoleak.

In addition, some patients have short common iliac arteries, an anatomy that is especially prevalent in patients of Asian descent and on the right side of the body. Dr. Lobato said that he developed the trifurcation technique to overcome these anatomical problems so that endovascular aneurysm repair could expand in a safe and cost-effective way via a method that was easy to perform.

Dr. Lobato broke the trifurcation technique into the following five steps:

▸ First, he inserts the main, bifurcated stent graft using an ipsilateral femoral approach. He positions the graft so that the distal end of the iliac limb is 1 cm above the origin of the internal iliac artery.

▸ Second, he inserts a long, 5-Fr multipurpose catheter into the ipsilateral internal iliac artery using left brachial access and a 0.035-inch, extra-stiff guide wire with a floppy tip.

▸ In the third step, he places a covered, self-expanding stent 2 cm into the internal iliac artery with a 6-cm overlap into the iliac limb. He also then positions an iliac limb extension 1 cm below the proximal end of the covered stent. He deploys the iliac limb extension first, followed by deployment of the covered stent.

▸ Fourth, he models the iliac limb stents with a latex balloon and dilates the covered stent with an angioplasty balloon.

▸ For the final, fifth step, he deploys the graft within the contralateral iliac limb.

In patients with bilateral aneurysms in their common iliac artery, he repeats steps 2–4 on the second side.

In all, 39 (95%) of the 41 treated internal iliac arteries maintained primary patency.

Source DR. LOBATO

Major Finding: A novel trifurcation technique safely preserved flow through the internal iliac arteries in patients who underwent an endovascular abdominal aortic aneurysm repair with an aneurysm in one or both common iliac arteries.

Data Source: A single-center series of 34 patients.

Disclosures: Dr. Lobato said that he had no disclosures.

MIAMI BEACH — A novel, trifurcated, endovascular stenting procedure allowed preservation of blood flow through the internal iliac artery of patients undergoing repair of a thoracoabdominal aortic aneurysm or an aortoiliac aneurysm.

Dr. Armando C. Lobato, who developed the technique, has successfully used it on 34 patients, including 7 patients who required bilateral repairs, he said at the meeting, sponsored by the Society of Interventional Radiology.

Dr. Lobato performed his first trifurcation procedure – which he also calls the Brazilian Sandwich procedure – in August 2008.

He reported having 100% technical success using the procedure, with no operative deaths and no need to convert to an open procedure.

During a median follow-up of 5 months (range, 2–24 months), no patient experienced colonic or buttock necrosis, no patient had ischemic colitis, and there were no type III endoleaks.

In all, 39 (95%) of the 41 treated internal iliac (hypogastric) arteries maintained primary patency. As a result of the procedure, occlusions also occurred in one contralateral iliac limb and in one ipsilateral external iliac artery. Secondary patency was maintained in 38 of the 41 treated arteries and their associated vessels, said Dr. Lobato, medical director of the Vascular and Endovascular Surgery Institute in São Paulo, Brazil.

About 20%–30% of patients with abdominal aortic aneurysm also have aneurysms in one or both of their common iliac arteries. Endovascular repair in these patients is harder because of the difficulty in finding an adequate landing zone for the stent-graft limbs and because the iliac aneurysm is a potential site for an endoleak.

In addition, some patients have short common iliac arteries, an anatomy that is especially prevalent in patients of Asian descent and on the right side of the body. Dr. Lobato said that he developed the trifurcation technique to overcome these anatomical problems so that endovascular aneurysm repair could expand in a safe and cost-effective way via a method that was easy to perform.

Dr. Lobato broke the trifurcation technique into the following five steps:

▸ First, he inserts the main, bifurcated stent graft using an ipsilateral femoral approach. He positions the graft so that the distal end of the iliac limb is 1 cm above the origin of the internal iliac artery.

▸ Second, he inserts a long, 5-Fr multipurpose catheter into the ipsilateral internal iliac artery using left brachial access and a 0.035-inch, extra-stiff guide wire with a floppy tip.

▸ In the third step, he places a covered, self-expanding stent 2 cm into the internal iliac artery with a 6-cm overlap into the iliac limb. He also then positions an iliac limb extension 1 cm below the proximal end of the covered stent. He deploys the iliac limb extension first, followed by deployment of the covered stent.

▸ Fourth, he models the iliac limb stents with a latex balloon and dilates the covered stent with an angioplasty balloon.

▸ For the final, fifth step, he deploys the graft within the contralateral iliac limb.

In patients with bilateral aneurysms in their common iliac artery, he repeats steps 2–4 on the second side.

In all, 39 (95%) of the 41 treated internal iliac arteries maintained primary patency.

Source DR. LOBATO

LOS ANGELES — Using retrievable stents to remove occluding clots from the cerebral arteries of acute ischemic stroke patients produced a high rate of recanalization and good safety in 3-month follow-up of 74 patients, the largest series of patients treated this way yet reported.

Removing clots from acute stroke patients using retrievable stents also required less time and fewer passes, with an average procedure duration of 45 minutes, Dr. Aitziber Aleu said at the conference.

“The advantage of stentrievers [retrievable stents] is that they are very easy to use and are faster to recanalize with fewer passes,” said Dr. Aleu, an interventional neurologist at Germans Trias i Pujol University Hospital, Barcelona. Retrievable stents “are now our first-line approach for acute stroke patients,” she said in an interview.

The series of 89 patients underwent treatment with a retrievable stent during March 2008 to December 2010. The operators used either of two brands of retrievable stents, the Solitaire or the Trevo, on roughly equal numbers of patients.

The average age of the patients was 66, and their average NIH Stroke Scale score at baseline was 18 (range, 15–22). Prior to stent placement, 48% of the patients had received treatment with tPA.

The average recanalization procedure took 45 minutes, with a range of 27–60 minutes, and each procedure required an average of 1.4 stent passes to remove the occluding blood clot. Stent deployment usually lasted less than a minute before retrieval, and the operators had no episodes of failed deployment. Stent treatment resulted in successful recanalization in 81 patients (91%), with 70% achieving a Thrombolysis in Cerebral Infarction flow rate of III, and 21% achieving TICI II flow.

Dr. Aleu presented 3-month follow-up results for 74 patients. At that time, 35 patients (47%) had a modified Rankin score of 2 or less, and 15 (20%) had died. During 3-month follow-up, 9% of the 74 patients had a symptomatic intracerebral hemorrhage.

Dr. Aleu said that she and her associates on the study had no disclosures.

In all, 91% of patients were successfully recanalized; 70% achieved TICI III flow and 21% reached TICI II.

Source DR. ALEU

View on the News

Next-Gen Stent

Stent retrievers are the next generation revascularization tool for acute stroke patients.

I have used the Solitaire stent as part of the SWIFT study, which is randomizing acute stroke patients to clot removal with either the Solitaire stent or the Merci retriever. I find this retrievable stent to be much more torqueable and navigable than other intracerebral devices.

With 47% of patients having a modified Rankin score of 2 or less at 3-month follow-up, Dr. Aleu and colleagues have approached the 50% level that I believe is the next goal for endovascular treatment of acute stroke.

ADNAN H. SIDDIQUI, M.D., is a neurosurgeon and director of the stroke program at the State University of New York at Buffalo. He has served as a consultant to ev3, which markets Solitaire.

LOS ANGELES — Using retrievable stents to remove occluding clots from the cerebral arteries of acute ischemic stroke patients produced a high rate of recanalization and good safety in 3-month follow-up of 74 patients, the largest series of patients treated this way yet reported.

Removing clots from acute stroke patients using retrievable stents also required less time and fewer passes, with an average procedure duration of 45 minutes, Dr. Aitziber Aleu said at the conference.

“The advantage of stentrievers [retrievable stents] is that they are very easy to use and are faster to recanalize with fewer passes,” said Dr. Aleu, an interventional neurologist at Germans Trias i Pujol University Hospital, Barcelona. Retrievable stents “are now our first-line approach for acute stroke patients,” she said in an interview.

The series of 89 patients underwent treatment with a retrievable stent during March 2008 to December 2010. The operators used either of two brands of retrievable stents, the Solitaire or the Trevo, on roughly equal numbers of patients.

The average age of the patients was 66, and their average NIH Stroke Scale score at baseline was 18 (range, 15–22). Prior to stent placement, 48% of the patients had received treatment with tPA.

The average recanalization procedure took 45 minutes, with a range of 27–60 minutes, and each procedure required an average of 1.4 stent passes to remove the occluding blood clot. Stent deployment usually lasted less than a minute before retrieval, and the operators had no episodes of failed deployment. Stent treatment resulted in successful recanalization in 81 patients (91%), with 70% achieving a Thrombolysis in Cerebral Infarction flow rate of III, and 21% achieving TICI II flow.

Dr. Aleu presented 3-month follow-up results for 74 patients. At that time, 35 patients (47%) had a modified Rankin score of 2 or less, and 15 (20%) had died. During 3-month follow-up, 9% of the 74 patients had a symptomatic intracerebral hemorrhage.

Dr. Aleu said that she and her associates on the study had no disclosures.

In all, 91% of patients were successfully recanalized; 70% achieved TICI III flow and 21% reached TICI II.

Source DR. ALEU

View on the News

Next-Gen Stent

Stent retrievers are the next generation revascularization tool for acute stroke patients.

I have used the Solitaire stent as part of the SWIFT study, which is randomizing acute stroke patients to clot removal with either the Solitaire stent or the Merci retriever. I find this retrievable stent to be much more torqueable and navigable than other intracerebral devices.

With 47% of patients having a modified Rankin score of 2 or less at 3-month follow-up, Dr. Aleu and colleagues have approached the 50% level that I believe is the next goal for endovascular treatment of acute stroke.

ADNAN H. SIDDIQUI, M.D., is a neurosurgeon and director of the stroke program at the State University of New York at Buffalo. He has served as a consultant to ev3, which markets Solitaire.

LOS ANGELES — Using retrievable stents to remove occluding clots from the cerebral arteries of acute ischemic stroke patients produced a high rate of recanalization and good safety in 3-month follow-up of 74 patients, the largest series of patients treated this way yet reported.

Removing clots from acute stroke patients using retrievable stents also required less time and fewer passes, with an average procedure duration of 45 minutes, Dr. Aitziber Aleu said at the conference.

“The advantage of stentrievers [retrievable stents] is that they are very easy to use and are faster to recanalize with fewer passes,” said Dr. Aleu, an interventional neurologist at Germans Trias i Pujol University Hospital, Barcelona. Retrievable stents “are now our first-line approach for acute stroke patients,” she said in an interview.

The series of 89 patients underwent treatment with a retrievable stent during March 2008 to December 2010. The operators used either of two brands of retrievable stents, the Solitaire or the Trevo, on roughly equal numbers of patients.

The average age of the patients was 66, and their average NIH Stroke Scale score at baseline was 18 (range, 15–22). Prior to stent placement, 48% of the patients had received treatment with tPA.

The average recanalization procedure took 45 minutes, with a range of 27–60 minutes, and each procedure required an average of 1.4 stent passes to remove the occluding blood clot. Stent deployment usually lasted less than a minute before retrieval, and the operators had no episodes of failed deployment. Stent treatment resulted in successful recanalization in 81 patients (91%), with 70% achieving a Thrombolysis in Cerebral Infarction flow rate of III, and 21% achieving TICI II flow.

Dr. Aleu presented 3-month follow-up results for 74 patients. At that time, 35 patients (47%) had a modified Rankin score of 2 or less, and 15 (20%) had died. During 3-month follow-up, 9% of the 74 patients had a symptomatic intracerebral hemorrhage.

Dr. Aleu said that she and her associates on the study had no disclosures.

In all, 91% of patients were successfully recanalized; 70% achieved TICI III flow and 21% reached TICI II.

Source DR. ALEU

View on the News

Next-Gen Stent

Stent retrievers are the next generation revascularization tool for acute stroke patients.

I have used the Solitaire stent as part of the SWIFT study, which is randomizing acute stroke patients to clot removal with either the Solitaire stent or the Merci retriever. I find this retrievable stent to be much more torqueable and navigable than other intracerebral devices.

With 47% of patients having a modified Rankin score of 2 or less at 3-month follow-up, Dr. Aleu and colleagues have approached the 50% level that I believe is the next goal for endovascular treatment of acute stroke.

ADNAN H. SIDDIQUI, M.D., is a neurosurgeon and director of the stroke program at the State University of New York at Buffalo. He has served as a consultant to ev3, which markets Solitaire.

LOS ANGELES — Barely more than a quarter of all U.S. acute stroke patients eligible for treatment with intravenous tissue plasminogen activator received the drug within an hour after arriving at the hospital, according to a registry of more than 1,000 U.S. hospitals dedicated to evidence-based stroke care during 2003–2009.

Among the 641 hospitals in the registry that treated at least 10 stroke patients with intravenous tPA within 3 hours of symptom onset, only 7% of the hospitals achieved a door-to-needle time of 60 minutes or less in a majority of their patients, Dr. Gregg C. Fonarow said at the conference. U.S. guidelines call for administering tPA to eligible stroke patients within an hour of their arrival at primary or comprehensive stroke centers.

The analysis also showed that the patients who appropriately received IV tPA within an hour of hospitalization had a significant 1.8% absolute reduction in in-hospital mortality, from 10.4% in patients whose tPA dose was delayed beyond 1 hour to 8.6%. The results “identify substantial opportunities for improvement in the speed of tPA therapy,” said Dr. Fonarow, professor of medicine and associate chief of cardiology University of California, Los Angeles.

Further analysis showed that after adjustment for possible confounders, every 15-minute reduction in the door-to-needle time for tPA linked with a significant 5% relative reduction in in-hospital mortality.

Patients who received intravenous tPA within an hour of arrival also had a significantly higher rate of discharge to a rehabilitation facility and a reduced rate of needing discharge to a nursing facility or another hospital, and significantly fewer tPA complications, including a 0.9% reduction in symptomatic intracranial hemorrhages, from 5.6% in patients who received tPA beyond 1 hour to 4.7% in those treated within 1 hour.

The analysis used data collected during April 2003–September 2009 on nearly 600,000 patients with an acute ischemic stroke admitted to one of 1,259 U.S. hospitals participating in the Get With the Guidelines stroke registry of the American Heart Association and the American Stroke Association.

The analysis included only the 25,504 patients who received tPA within 3 hours of their symptom onset at 1,082 hospitals in the registry. Throughout the 6.5 years of the study, the door-to-needle time averaged 79 minutes, with 6,790 patients (27%) receiving tPA within an hour. During the study period, average door-to-needle time improved modestly, from 85 minutes in 2003 to 75 minutes in 2009.

Concurrent with Dr. Fonarow's report, the results were published online (Circulation 2011 Feb. 10 [doi:10.1161/CIRCULATIONAHA.110.974675]).

Dr. Fonarow has been a consultant to Pfizer, Merck, Schering Plough, Bristol Myers Squibb, and Sanofi-Aventis. He is an employee of the University of California, which holds a patent on retriever devices for treating acute stroke.

Only 7% of the hospitals achieved a door-to-needle time of 60 minutes or less in most of their patients.

Source DR. FONAROW

View on the News

Blunt Motivators May Speed tPA Use

It's a mistake to think that there is a one-size-fits-all intervention that will improve and speed up tPA use at all hospitals. The big stick approach stands a better chance of working, one that involves regulatory agencies or payers. If there were a stroke DRG (diagnosis-related group) that said stroke patients should receive tPA within 30 minutes, hospitals would figure out how to do it pretty quickly.

The 1.8% improved in-hospital mortality that Dr. Fonarow reports for patients treated with tPA within an hour of arriving at the hospital is significant, but I suspect the mortality improvement did not completely result from faster tPA treatment. Faster tPA use may be a marker for hospitals that are better organized and do a lot of things better for their stroke patients, which together maximize the stroke patients' survival.

WILLIAM J. MEURER, M.D., is a neurologist and emergency medicine physician at the University of Michigan in Ann Arbor. He reported having no disclosures.

LOS ANGELES — Barely more than a quarter of all U.S. acute stroke patients eligible for treatment with intravenous tissue plasminogen activator received the drug within an hour after arriving at the hospital, according to a registry of more than 1,000 U.S. hospitals dedicated to evidence-based stroke care during 2003–2009.

Among the 641 hospitals in the registry that treated at least 10 stroke patients with intravenous tPA within 3 hours of symptom onset, only 7% of the hospitals achieved a door-to-needle time of 60 minutes or less in a majority of their patients, Dr. Gregg C. Fonarow said at the conference. U.S. guidelines call for administering tPA to eligible stroke patients within an hour of their arrival at primary or comprehensive stroke centers.

The analysis also showed that the patients who appropriately received IV tPA within an hour of hospitalization had a significant 1.8% absolute reduction in in-hospital mortality, from 10.4% in patients whose tPA dose was delayed beyond 1 hour to 8.6%. The results “identify substantial opportunities for improvement in the speed of tPA therapy,” said Dr. Fonarow, professor of medicine and associate chief of cardiology University of California, Los Angeles.

Further analysis showed that after adjustment for possible confounders, every 15-minute reduction in the door-to-needle time for tPA linked with a significant 5% relative reduction in in-hospital mortality.

Patients who received intravenous tPA within an hour of arrival also had a significantly higher rate of discharge to a rehabilitation facility and a reduced rate of needing discharge to a nursing facility or another hospital, and significantly fewer tPA complications, including a 0.9% reduction in symptomatic intracranial hemorrhages, from 5.6% in patients who received tPA beyond 1 hour to 4.7% in those treated within 1 hour.

The analysis used data collected during April 2003–September 2009 on nearly 600,000 patients with an acute ischemic stroke admitted to one of 1,259 U.S. hospitals participating in the Get With the Guidelines stroke registry of the American Heart Association and the American Stroke Association.

The analysis included only the 25,504 patients who received tPA within 3 hours of their symptom onset at 1,082 hospitals in the registry. Throughout the 6.5 years of the study, the door-to-needle time averaged 79 minutes, with 6,790 patients (27%) receiving tPA within an hour. During the study period, average door-to-needle time improved modestly, from 85 minutes in 2003 to 75 minutes in 2009.

Concurrent with Dr. Fonarow's report, the results were published online (Circulation 2011 Feb. 10 [doi:10.1161/CIRCULATIONAHA.110.974675]).

Dr. Fonarow has been a consultant to Pfizer, Merck, Schering Plough, Bristol Myers Squibb, and Sanofi-Aventis. He is an employee of the University of California, which holds a patent on retriever devices for treating acute stroke.

Only 7% of the hospitals achieved a door-to-needle time of 60 minutes or less in most of their patients.

Source DR. FONAROW

View on the News

Blunt Motivators May Speed tPA Use

It's a mistake to think that there is a one-size-fits-all intervention that will improve and speed up tPA use at all hospitals. The big stick approach stands a better chance of working, one that involves regulatory agencies or payers. If there were a stroke DRG (diagnosis-related group) that said stroke patients should receive tPA within 30 minutes, hospitals would figure out how to do it pretty quickly.

The 1.8% improved in-hospital mortality that Dr. Fonarow reports for patients treated with tPA within an hour of arriving at the hospital is significant, but I suspect the mortality improvement did not completely result from faster tPA treatment. Faster tPA use may be a marker for hospitals that are better organized and do a lot of things better for their stroke patients, which together maximize the stroke patients' survival.

WILLIAM J. MEURER, M.D., is a neurologist and emergency medicine physician at the University of Michigan in Ann Arbor. He reported having no disclosures.

LOS ANGELES — Barely more than a quarter of all U.S. acute stroke patients eligible for treatment with intravenous tissue plasminogen activator received the drug within an hour after arriving at the hospital, according to a registry of more than 1,000 U.S. hospitals dedicated to evidence-based stroke care during 2003–2009.

Among the 641 hospitals in the registry that treated at least 10 stroke patients with intravenous tPA within 3 hours of symptom onset, only 7% of the hospitals achieved a door-to-needle time of 60 minutes or less in a majority of their patients, Dr. Gregg C. Fonarow said at the conference. U.S. guidelines call for administering tPA to eligible stroke patients within an hour of their arrival at primary or comprehensive stroke centers.

The analysis also showed that the patients who appropriately received IV tPA within an hour of hospitalization had a significant 1.8% absolute reduction in in-hospital mortality, from 10.4% in patients whose tPA dose was delayed beyond 1 hour to 8.6%. The results “identify substantial opportunities for improvement in the speed of tPA therapy,” said Dr. Fonarow, professor of medicine and associate chief of cardiology University of California, Los Angeles.

Further analysis showed that after adjustment for possible confounders, every 15-minute reduction in the door-to-needle time for tPA linked with a significant 5% relative reduction in in-hospital mortality.

Patients who received intravenous tPA within an hour of arrival also had a significantly higher rate of discharge to a rehabilitation facility and a reduced rate of needing discharge to a nursing facility or another hospital, and significantly fewer tPA complications, including a 0.9% reduction in symptomatic intracranial hemorrhages, from 5.6% in patients who received tPA beyond 1 hour to 4.7% in those treated within 1 hour.

The analysis used data collected during April 2003–September 2009 on nearly 600,000 patients with an acute ischemic stroke admitted to one of 1,259 U.S. hospitals participating in the Get With the Guidelines stroke registry of the American Heart Association and the American Stroke Association.

The analysis included only the 25,504 patients who received tPA within 3 hours of their symptom onset at 1,082 hospitals in the registry. Throughout the 6.5 years of the study, the door-to-needle time averaged 79 minutes, with 6,790 patients (27%) receiving tPA within an hour. During the study period, average door-to-needle time improved modestly, from 85 minutes in 2003 to 75 minutes in 2009.

Concurrent with Dr. Fonarow's report, the results were published online (Circulation 2011 Feb. 10 [doi:10.1161/CIRCULATIONAHA.110.974675]).

Dr. Fonarow has been a consultant to Pfizer, Merck, Schering Plough, Bristol Myers Squibb, and Sanofi-Aventis. He is an employee of the University of California, which holds a patent on retriever devices for treating acute stroke.

Only 7% of the hospitals achieved a door-to-needle time of 60 minutes or less in most of their patients.

Source DR. FONAROW

View on the News

Blunt Motivators May Speed tPA Use

It's a mistake to think that there is a one-size-fits-all intervention that will improve and speed up tPA use at all hospitals. The big stick approach stands a better chance of working, one that involves regulatory agencies or payers. If there were a stroke DRG (diagnosis-related group) that said stroke patients should receive tPA within 30 minutes, hospitals would figure out how to do it pretty quickly.

The 1.8% improved in-hospital mortality that Dr. Fonarow reports for patients treated with tPA within an hour of arriving at the hospital is significant, but I suspect the mortality improvement did not completely result from faster tPA treatment. Faster tPA use may be a marker for hospitals that are better organized and do a lot of things better for their stroke patients, which together maximize the stroke patients' survival.

WILLIAM J. MEURER, M.D., is a neurologist and emergency medicine physician at the University of Michigan in Ann Arbor. He reported having no disclosures.

LOS ANGELES – Starting or maintaining acute stroke patients on a statin during their initial hospitalization was linked with a dramatic improvement in 1-year survival in a retrospective review of medical records for more than 12,000 U.S. patients.

Based on the finding, Kaiser Permanente of Northern California will issue a revised order set that will recommend to physicians that they start acute stroke patients on 80-mg simvastatin as soon as possible on the first day of their hospitalization, Dr. Alexander C. Flint said at the International Stroke Conference.

"Based on results from the SPARCL [Stroke Prevention by Aggressive Reduction in Cholesterol Levels] trial, pretty much everyone in the stroke community believes that patients who have had an ischemic stroke should be treated with high-dose statin to prevent a second stroke (N. Engl. J. Med. 2006;355:549-59). In our study, the question wasn’t whether to treat, but the timing. What our results say is that you should not wait until the patient is discharged or is an outpatient, but that you should start the statin on day 1," Dr. Flint said in an interview.

The data he reported showed that stroke patients who started on a statin during their acute-phase hospitalization had a 15% absolute reduced rate of death during the first year following their stroke, compared with patients who did not start on a statin and did not receive a statin prior to their stroke (Stroke 2011;42:e-42-110). After adjustment for several possible confounding factors, including age; sex; race and ethnicity; year of stroke; and comorbidities such as hypertension and diabetes, stroke patients who started on a statin while hospitalized had a statistically significant (45%) relatively lower risk of death during the subsequent year, compared with patients who did not receive a statin.

The study involved 12,689 patients who received care from Kaiser Permanente of Northern California and had an ischemic stroke during 2000-2007. The total included 3,749 patients who were on steady statin treatment for at least 3 months before their stroke, and 8,940 patients who were not receiving a statin at all before their stroke.* Of the 3,749 patients who were on a statin before their stroke, most (3,280, or 87%) continued to receive a statin during their hospitalization. And among the 8,940 who did not receive regular statin treatment before their stroke, 3,013 (34%) began statin treatment while hospitalized.

Patients who received a statin prior to their stroke but did not continue while hospitalized had a statistically significant 15% relative reduction in their mortality during the following year, compared with patients who never received a statin.

The key element for mortality protection appeared to be treatment while hospitalized. Relative mortality reduction compared with nonstatin users was 41% among patients who were on a statin both before their stroke and while hospitalized, and 45% among those who started on a statin while hospitalized, said Dr. Flint, a neurointensivist and stroke specialist at Kaiser Redwood City (Calif.). Patients who received a statin before their stroke but discontinued the drug once hospitalized had the worst outcomes, with a mortality rate that was 2.5-fold higher than that of patients who never received a statin.

Further analysis highlighted the importance of an early start to statin treatment in hospitalized patients, and also showed a dose-response relationship. Patients who received at least 60 mg of their statin daily either before hospitalization or both before and during hospitalization had a significantly lower mortality rate, compared with patients who took less than 60 mg/day. Dr. Flint noted that about 70% of patients received lovastatin, and about 20% received simvastatin.

Regarding timing, patients who either began on a statin for the first time or restarted their treatment on their first hospitalized day had a significantly lower 1-year mortality, compared with patients who did not start or restart their statin until their third day in hospital.

Dr. Flint also reported an additional analysis that had been run to determine whether patients’ survival prognosis drove their statin treatment instead of their statin treatment’s driving their survival. To do this, he looked at patterns of care at each of the 17 Kaiser Permanente of Northern California hospitals that were involved in the study. This "grouped treatment analysis" showed that although the survival prognosis of patients who were withdrawn from prior statin treatment while hospitalized played some role in the relationship, it was unable to explain all of the survival effect, indicating that statin treatment itself during hospitalization played a significant role in subsequent survival.

The strong impact that early statin treatment during stroke hospitalization has on long-term survival probably depends on the pleiotropic effects of statins. The timing makes it less likely that the effect of statins on lipid levels can explain the observed survival benefits, Dr. Flint said.

Dr. Flint said that he had no disclosures.

* CORRECTION, 3/4/2011: An earlier version of this article stated that some study participants took statins intermittently prior to having a stroke. However, the study included only patients who were taking a statin for at least 3 months prior to the stroke or those not taking a statin at all. This version has been updated.

LOS ANGELES – Starting or maintaining acute stroke patients on a statin during their initial hospitalization was linked with a dramatic improvement in 1-year survival in a retrospective review of medical records for more than 12,000 U.S. patients.

Based on the finding, Kaiser Permanente of Northern California will issue a revised order set that will recommend to physicians that they start acute stroke patients on 80-mg simvastatin as soon as possible on the first day of their hospitalization, Dr. Alexander C. Flint said at the International Stroke Conference.

"Based on results from the SPARCL [Stroke Prevention by Aggressive Reduction in Cholesterol Levels] trial, pretty much everyone in the stroke community believes that patients who have had an ischemic stroke should be treated with high-dose statin to prevent a second stroke (N. Engl. J. Med. 2006;355:549-59). In our study, the question wasn’t whether to treat, but the timing. What our results say is that you should not wait until the patient is discharged or is an outpatient, but that you should start the statin on day 1," Dr. Flint said in an interview.

The data he reported showed that stroke patients who started on a statin during their acute-phase hospitalization had a 15% absolute reduced rate of death during the first year following their stroke, compared with patients who did not start on a statin and did not receive a statin prior to their stroke (Stroke 2011;42:e-42-110). After adjustment for several possible confounding factors, including age; sex; race and ethnicity; year of stroke; and comorbidities such as hypertension and diabetes, stroke patients who started on a statin while hospitalized had a statistically significant (45%) relatively lower risk of death during the subsequent year, compared with patients who did not receive a statin.

The study involved 12,689 patients who received care from Kaiser Permanente of Northern California and had an ischemic stroke during 2000-2007. The total included 3,749 patients who were on steady statin treatment for at least 3 months before their stroke, and 8,940 patients who were not receiving a statin at all before their stroke.* Of the 3,749 patients who were on a statin before their stroke, most (3,280, or 87%) continued to receive a statin during their hospitalization. And among the 8,940 who did not receive regular statin treatment before their stroke, 3,013 (34%) began statin treatment while hospitalized.

Patients who received a statin prior to their stroke but did not continue while hospitalized had a statistically significant 15% relative reduction in their mortality during the following year, compared with patients who never received a statin.

The key element for mortality protection appeared to be treatment while hospitalized. Relative mortality reduction compared with nonstatin users was 41% among patients who were on a statin both before their stroke and while hospitalized, and 45% among those who started on a statin while hospitalized, said Dr. Flint, a neurointensivist and stroke specialist at Kaiser Redwood City (Calif.). Patients who received a statin before their stroke but discontinued the drug once hospitalized had the worst outcomes, with a mortality rate that was 2.5-fold higher than that of patients who never received a statin.

Further analysis highlighted the importance of an early start to statin treatment in hospitalized patients, and also showed a dose-response relationship. Patients who received at least 60 mg of their statin daily either before hospitalization or both before and during hospitalization had a significantly lower mortality rate, compared with patients who took less than 60 mg/day. Dr. Flint noted that about 70% of patients received lovastatin, and about 20% received simvastatin.

Regarding timing, patients who either began on a statin for the first time or restarted their treatment on their first hospitalized day had a significantly lower 1-year mortality, compared with patients who did not start or restart their statin until their third day in hospital.

Dr. Flint also reported an additional analysis that had been run to determine whether patients’ survival prognosis drove their statin treatment instead of their statin treatment’s driving their survival. To do this, he looked at patterns of care at each of the 17 Kaiser Permanente of Northern California hospitals that were involved in the study. This "grouped treatment analysis" showed that although the survival prognosis of patients who were withdrawn from prior statin treatment while hospitalized played some role in the relationship, it was unable to explain all of the survival effect, indicating that statin treatment itself during hospitalization played a significant role in subsequent survival.

The strong impact that early statin treatment during stroke hospitalization has on long-term survival probably depends on the pleiotropic effects of statins. The timing makes it less likely that the effect of statins on lipid levels can explain the observed survival benefits, Dr. Flint said.

Dr. Flint said that he had no disclosures.

* CORRECTION, 3/4/2011: An earlier version of this article stated that some study participants took statins intermittently prior to having a stroke. However, the study included only patients who were taking a statin for at least 3 months prior to the stroke or those not taking a statin at all. This version has been updated.

LOS ANGELES – Starting or maintaining acute stroke patients on a statin during their initial hospitalization was linked with a dramatic improvement in 1-year survival in a retrospective review of medical records for more than 12,000 U.S. patients.

Based on the finding, Kaiser Permanente of Northern California will issue a revised order set that will recommend to physicians that they start acute stroke patients on 80-mg simvastatin as soon as possible on the first day of their hospitalization, Dr. Alexander C. Flint said at the International Stroke Conference.

"Based on results from the SPARCL [Stroke Prevention by Aggressive Reduction in Cholesterol Levels] trial, pretty much everyone in the stroke community believes that patients who have had an ischemic stroke should be treated with high-dose statin to prevent a second stroke (N. Engl. J. Med. 2006;355:549-59). In our study, the question wasn’t whether to treat, but the timing. What our results say is that you should not wait until the patient is discharged or is an outpatient, but that you should start the statin on day 1," Dr. Flint said in an interview.

The data he reported showed that stroke patients who started on a statin during their acute-phase hospitalization had a 15% absolute reduced rate of death during the first year following their stroke, compared with patients who did not start on a statin and did not receive a statin prior to their stroke (Stroke 2011;42:e-42-110). After adjustment for several possible confounding factors, including age; sex; race and ethnicity; year of stroke; and comorbidities such as hypertension and diabetes, stroke patients who started on a statin while hospitalized had a statistically significant (45%) relatively lower risk of death during the subsequent year, compared with patients who did not receive a statin.

The study involved 12,689 patients who received care from Kaiser Permanente of Northern California and had an ischemic stroke during 2000-2007. The total included 3,749 patients who were on steady statin treatment for at least 3 months before their stroke, and 8,940 patients who were not receiving a statin at all before their stroke.* Of the 3,749 patients who were on a statin before their stroke, most (3,280, or 87%) continued to receive a statin during their hospitalization. And among the 8,940 who did not receive regular statin treatment before their stroke, 3,013 (34%) began statin treatment while hospitalized.

Patients who received a statin prior to their stroke but did not continue while hospitalized had a statistically significant 15% relative reduction in their mortality during the following year, compared with patients who never received a statin.

The key element for mortality protection appeared to be treatment while hospitalized. Relative mortality reduction compared with nonstatin users was 41% among patients who were on a statin both before their stroke and while hospitalized, and 45% among those who started on a statin while hospitalized, said Dr. Flint, a neurointensivist and stroke specialist at Kaiser Redwood City (Calif.). Patients who received a statin before their stroke but discontinued the drug once hospitalized had the worst outcomes, with a mortality rate that was 2.5-fold higher than that of patients who never received a statin.

Further analysis highlighted the importance of an early start to statin treatment in hospitalized patients, and also showed a dose-response relationship. Patients who received at least 60 mg of their statin daily either before hospitalization or both before and during hospitalization had a significantly lower mortality rate, compared with patients who took less than 60 mg/day. Dr. Flint noted that about 70% of patients received lovastatin, and about 20% received simvastatin.

Regarding timing, patients who either began on a statin for the first time or restarted their treatment on their first hospitalized day had a significantly lower 1-year mortality, compared with patients who did not start or restart their statin until their third day in hospital.

Dr. Flint also reported an additional analysis that had been run to determine whether patients’ survival prognosis drove their statin treatment instead of their statin treatment’s driving their survival. To do this, he looked at patterns of care at each of the 17 Kaiser Permanente of Northern California hospitals that were involved in the study. This "grouped treatment analysis" showed that although the survival prognosis of patients who were withdrawn from prior statin treatment while hospitalized played some role in the relationship, it was unable to explain all of the survival effect, indicating that statin treatment itself during hospitalization played a significant role in subsequent survival.

The strong impact that early statin treatment during stroke hospitalization has on long-term survival probably depends on the pleiotropic effects of statins. The timing makes it less likely that the effect of statins on lipid levels can explain the observed survival benefits, Dr. Flint said.

Dr. Flint said that he had no disclosures.

* CORRECTION, 3/4/2011: An earlier version of this article stated that some study participants took statins intermittently prior to having a stroke. However, the study included only patients who were taking a statin for at least 3 months prior to the stroke or those not taking a statin at all. This version has been updated.