Mitchel L. Zoler, PhD

Major Finding: Acute myocardial infarction patients treated with drug-eluting coronary stents had a 16% mortality rate during 5 years of follow-up, significantly better than the 20% mortality rate in patients treated with bare-metal stents.

Data Source: Review of 12,005 New Jersey patients treated with primary percutaneous coronary intervention during 2003-2004.

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

NEW ORLEANS – Acute myocardial infarction patients treated with a drug-eluting coronary stent during a primary percutaneous coronary intervention had significantly better 5-year survival, compared with myocardial infarction patients who received a bare-metal stent, in a review of more than 12,000 patients treated in New Jersey during 2003-2004.

Although this analysis could not take into account selection biases that might have determined whether patients received drug-eluting or bare-metal stents, the findings in general provide reassurance about the safety of drug-eluting coronary stents for patients with an acute MI, Dr. Tudor D. Vagaonescu said at the meeting.

“These data are consistent with the idea that using drug-eluting stents in the setting of an acute MI is safe,” said Dr. Vagaonescu, a cardiologist at the Robert Wood Johnson Medical School, New Brunswick, N.J.

“Our data show that preventing the need for revascularization by using drug-eluting stents [DES] helped with survival, although improved survival was likely due to a combination of things, including selection bias and the type of index event,” he said in an interview.

The study used data collected in the Myocardial Infarction Data Acquisition System (MIDAS) registry and included all patients who underwent primary PCI for an acute MI at a nonfederal hospital in New Jersey during 2003-2004. The group included 6,172 patients treated with one or more drug-eluting coronary stents only, and 5,833 patients treated with one or more bare-metal stents only. The analysis excluded patients who received both stent types.

Based on New Jersey death registration files, during the 5 years following stent placement, cumulative all-cause mortality in the DES recipients was 16% and was 20% in the bare-metal stent recipients, a statistically significant difference. The rate of cardiovascular death was 8% and 10% in the drug-eluting and bare-metal stent groups, respectively, also a statistically significant difference. Similar, statistically significant differences in favor of improved 5-year total survival and reduced cardiovascular deaths with DES also occurred in both the subset of patients with ST-elevation myocardial infarction and in patients with non–ST-elevation myocardial infarction, Dr. Vagaonescu reported.

He and his associates also performed multivariate analyses of mortality rates adjusted by age, sex, race, diabetes, hypertension, renal disease, anemia, cancer, cerebrovascular disease, prior MI, and treatment with a glycoprotein IIb/IIIa inhibitor. All of these multivariate analyses showed statistically significant survival advantages for the patients who received drug-eluting stents (see graph).

Another aspect of the analysis showed the dramatic shift toward use of DES for primary PCI during the period studied, which covered the time when the first sirolimus-eluting stent received Food and Drug Administration approval in April 2003, and when the first paclitaxel-eluting coronary stent received FDA approval in March 2004. In 2003, 73% of the 6,027 patients who received a single type of coronary stent for primary PCI in New Jersey received a bare-metal stent. By 2004, this pattern flipped, and 76% of the 5,978 patients who received a single type of coronary stent for primary PCI received a drug-eluting stent. Both years predated the reports in 2006 that first raised awareness of the risk for stent thrombosis in patients who received a DES, especially patients who prematurely stopped dual-antiplatelet therapy.

Vitals

Source Elsevier Global Medical News

View on the News

Jury Out on First-Generation DES

A major concern when using drug-eluting coronary stents to treat acute myocardial infarction is the risk of late stent thrombosis, especially with the first-generation drug-eluting stents, the sirolimus-eluting Cypher and the paclitaxel-eluting Taxus stents.

For several years, since evidence established a link between long-term dual-antiplatelet therapy and reduced stent thrombosis, the issue has been can an acute myocardial infarction patient reliably remain on dual-antiplatelet therapy for at least 1 year. This information is often difficult to know in the emergency department at the time of primary percutaneous coronary intervention.

This concern has been balanced by the very respectable performance of bare-metal stents when placed in acute myocardial infarction patients. Experience has taught us that when you have doubt about a patient's willingness or ability to remain on dual-antiplatelet therapy, there is nothing wrong with using a bare-metal stent.

What's unclear is the potential role for the second-generation drug eluting stents for primary percutaneous coronary interventions. The everolimus-eluting stents seem to have a reduced risk for late thrombosis, compared with the first-generation stents in patients without an acute myocardial infarction. We'd like to know the performance of second-generation drug-eluting stents in myocardial infarction patients, but we currently have no evidence about this.

The data presented by Dr. Vagaonescu do not provide a solid case for using first-generation drug-eluting stents in myocardial infarction patients. These data came from a retrospective review, and the patients involved were very heterogeneous. It's just a first step toward understanding, in a broad group of patients, how drug-eluting and bare-metal stents perform in myocardial infarction patients.

DAVID G. RIZK, M.D., is an interventional cardiologist and director of the division of heart and vascular medicine at the Scottsdale (Ariz.) Healthcare Hospital. His comments were made in an interview. He said that he had no disclosures.

Major Finding: Acute myocardial infarction patients treated with drug-eluting coronary stents had a 16% mortality rate during 5 years of follow-up, significantly better than the 20% mortality rate in patients treated with bare-metal stents.

Data Source: Review of 12,005 New Jersey patients treated with primary percutaneous coronary intervention during 2003-2004.

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

NEW ORLEANS – Acute myocardial infarction patients treated with a drug-eluting coronary stent during a primary percutaneous coronary intervention had significantly better 5-year survival, compared with myocardial infarction patients who received a bare-metal stent, in a review of more than 12,000 patients treated in New Jersey during 2003-2004.

Although this analysis could not take into account selection biases that might have determined whether patients received drug-eluting or bare-metal stents, the findings in general provide reassurance about the safety of drug-eluting coronary stents for patients with an acute MI, Dr. Tudor D. Vagaonescu said at the meeting.

“These data are consistent with the idea that using drug-eluting stents in the setting of an acute MI is safe,” said Dr. Vagaonescu, a cardiologist at the Robert Wood Johnson Medical School, New Brunswick, N.J.

“Our data show that preventing the need for revascularization by using drug-eluting stents [DES] helped with survival, although improved survival was likely due to a combination of things, including selection bias and the type of index event,” he said in an interview.

The study used data collected in the Myocardial Infarction Data Acquisition System (MIDAS) registry and included all patients who underwent primary PCI for an acute MI at a nonfederal hospital in New Jersey during 2003-2004. The group included 6,172 patients treated with one or more drug-eluting coronary stents only, and 5,833 patients treated with one or more bare-metal stents only. The analysis excluded patients who received both stent types.

Based on New Jersey death registration files, during the 5 years following stent placement, cumulative all-cause mortality in the DES recipients was 16% and was 20% in the bare-metal stent recipients, a statistically significant difference. The rate of cardiovascular death was 8% and 10% in the drug-eluting and bare-metal stent groups, respectively, also a statistically significant difference. Similar, statistically significant differences in favor of improved 5-year total survival and reduced cardiovascular deaths with DES also occurred in both the subset of patients with ST-elevation myocardial infarction and in patients with non–ST-elevation myocardial infarction, Dr. Vagaonescu reported.

He and his associates also performed multivariate analyses of mortality rates adjusted by age, sex, race, diabetes, hypertension, renal disease, anemia, cancer, cerebrovascular disease, prior MI, and treatment with a glycoprotein IIb/IIIa inhibitor. All of these multivariate analyses showed statistically significant survival advantages for the patients who received drug-eluting stents (see graph).

Another aspect of the analysis showed the dramatic shift toward use of DES for primary PCI during the period studied, which covered the time when the first sirolimus-eluting stent received Food and Drug Administration approval in April 2003, and when the first paclitaxel-eluting coronary stent received FDA approval in March 2004. In 2003, 73% of the 6,027 patients who received a single type of coronary stent for primary PCI in New Jersey received a bare-metal stent. By 2004, this pattern flipped, and 76% of the 5,978 patients who received a single type of coronary stent for primary PCI received a drug-eluting stent. Both years predated the reports in 2006 that first raised awareness of the risk for stent thrombosis in patients who received a DES, especially patients who prematurely stopped dual-antiplatelet therapy.

Vitals

Source Elsevier Global Medical News

View on the News

Jury Out on First-Generation DES

A major concern when using drug-eluting coronary stents to treat acute myocardial infarction is the risk of late stent thrombosis, especially with the first-generation drug-eluting stents, the sirolimus-eluting Cypher and the paclitaxel-eluting Taxus stents.

For several years, since evidence established a link between long-term dual-antiplatelet therapy and reduced stent thrombosis, the issue has been can an acute myocardial infarction patient reliably remain on dual-antiplatelet therapy for at least 1 year. This information is often difficult to know in the emergency department at the time of primary percutaneous coronary intervention.

This concern has been balanced by the very respectable performance of bare-metal stents when placed in acute myocardial infarction patients. Experience has taught us that when you have doubt about a patient's willingness or ability to remain on dual-antiplatelet therapy, there is nothing wrong with using a bare-metal stent.

What's unclear is the potential role for the second-generation drug eluting stents for primary percutaneous coronary interventions. The everolimus-eluting stents seem to have a reduced risk for late thrombosis, compared with the first-generation stents in patients without an acute myocardial infarction. We'd like to know the performance of second-generation drug-eluting stents in myocardial infarction patients, but we currently have no evidence about this.

The data presented by Dr. Vagaonescu do not provide a solid case for using first-generation drug-eluting stents in myocardial infarction patients. These data came from a retrospective review, and the patients involved were very heterogeneous. It's just a first step toward understanding, in a broad group of patients, how drug-eluting and bare-metal stents perform in myocardial infarction patients.

DAVID G. RIZK, M.D., is an interventional cardiologist and director of the division of heart and vascular medicine at the Scottsdale (Ariz.) Healthcare Hospital. His comments were made in an interview. He said that he had no disclosures.

Major Finding: Acute myocardial infarction patients treated with drug-eluting coronary stents had a 16% mortality rate during 5 years of follow-up, significantly better than the 20% mortality rate in patients treated with bare-metal stents.

Data Source: Review of 12,005 New Jersey patients treated with primary percutaneous coronary intervention during 2003-2004.

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

NEW ORLEANS – Acute myocardial infarction patients treated with a drug-eluting coronary stent during a primary percutaneous coronary intervention had significantly better 5-year survival, compared with myocardial infarction patients who received a bare-metal stent, in a review of more than 12,000 patients treated in New Jersey during 2003-2004.

Although this analysis could not take into account selection biases that might have determined whether patients received drug-eluting or bare-metal stents, the findings in general provide reassurance about the safety of drug-eluting coronary stents for patients with an acute MI, Dr. Tudor D. Vagaonescu said at the meeting.

“These data are consistent with the idea that using drug-eluting stents in the setting of an acute MI is safe,” said Dr. Vagaonescu, a cardiologist at the Robert Wood Johnson Medical School, New Brunswick, N.J.

“Our data show that preventing the need for revascularization by using drug-eluting stents [DES] helped with survival, although improved survival was likely due to a combination of things, including selection bias and the type of index event,” he said in an interview.

The study used data collected in the Myocardial Infarction Data Acquisition System (MIDAS) registry and included all patients who underwent primary PCI for an acute MI at a nonfederal hospital in New Jersey during 2003-2004. The group included 6,172 patients treated with one or more drug-eluting coronary stents only, and 5,833 patients treated with one or more bare-metal stents only. The analysis excluded patients who received both stent types.

Based on New Jersey death registration files, during the 5 years following stent placement, cumulative all-cause mortality in the DES recipients was 16% and was 20% in the bare-metal stent recipients, a statistically significant difference. The rate of cardiovascular death was 8% and 10% in the drug-eluting and bare-metal stent groups, respectively, also a statistically significant difference. Similar, statistically significant differences in favor of improved 5-year total survival and reduced cardiovascular deaths with DES also occurred in both the subset of patients with ST-elevation myocardial infarction and in patients with non–ST-elevation myocardial infarction, Dr. Vagaonescu reported.

He and his associates also performed multivariate analyses of mortality rates adjusted by age, sex, race, diabetes, hypertension, renal disease, anemia, cancer, cerebrovascular disease, prior MI, and treatment with a glycoprotein IIb/IIIa inhibitor. All of these multivariate analyses showed statistically significant survival advantages for the patients who received drug-eluting stents (see graph).

Another aspect of the analysis showed the dramatic shift toward use of DES for primary PCI during the period studied, which covered the time when the first sirolimus-eluting stent received Food and Drug Administration approval in April 2003, and when the first paclitaxel-eluting coronary stent received FDA approval in March 2004. In 2003, 73% of the 6,027 patients who received a single type of coronary stent for primary PCI in New Jersey received a bare-metal stent. By 2004, this pattern flipped, and 76% of the 5,978 patients who received a single type of coronary stent for primary PCI received a drug-eluting stent. Both years predated the reports in 2006 that first raised awareness of the risk for stent thrombosis in patients who received a DES, especially patients who prematurely stopped dual-antiplatelet therapy.

Vitals

Source Elsevier Global Medical News

View on the News

Jury Out on First-Generation DES

A major concern when using drug-eluting coronary stents to treat acute myocardial infarction is the risk of late stent thrombosis, especially with the first-generation drug-eluting stents, the sirolimus-eluting Cypher and the paclitaxel-eluting Taxus stents.

For several years, since evidence established a link between long-term dual-antiplatelet therapy and reduced stent thrombosis, the issue has been can an acute myocardial infarction patient reliably remain on dual-antiplatelet therapy for at least 1 year. This information is often difficult to know in the emergency department at the time of primary percutaneous coronary intervention.

This concern has been balanced by the very respectable performance of bare-metal stents when placed in acute myocardial infarction patients. Experience has taught us that when you have doubt about a patient's willingness or ability to remain on dual-antiplatelet therapy, there is nothing wrong with using a bare-metal stent.

What's unclear is the potential role for the second-generation drug eluting stents for primary percutaneous coronary interventions. The everolimus-eluting stents seem to have a reduced risk for late thrombosis, compared with the first-generation stents in patients without an acute myocardial infarction. We'd like to know the performance of second-generation drug-eluting stents in myocardial infarction patients, but we currently have no evidence about this.

The data presented by Dr. Vagaonescu do not provide a solid case for using first-generation drug-eluting stents in myocardial infarction patients. These data came from a retrospective review, and the patients involved were very heterogeneous. It's just a first step toward understanding, in a broad group of patients, how drug-eluting and bare-metal stents perform in myocardial infarction patients.

DAVID G. RIZK, M.D., is an interventional cardiologist and director of the division of heart and vascular medicine at the Scottsdale (Ariz.) Healthcare Hospital. His comments were made in an interview. He said that he had no disclosures.

Major Finding: High-risk patients who were aided during PCI with an LVAD (Impella 2.5) had a 41% rate of major adverse events at 90 days, significantly better than the 51% rate in patients treated with a standard intra-aortic balloon pump. But in the intention-to-treat analysis, outcomes did not differ for the two groups at either 30 days or 90 days.

Data Source: PROTECT II, a randomized trial comparing LV support with the Impella 2.5 device and an intra-aortic balloon pump in 447 patients who were treated at 72 sites worldwide.

Disclosures: PROTECT II was funded by Abiomed, which markets the Impella device. Dr. O'Neill has been a consultant to Medtronic. Dr. Waksman has been a consultant to or received honoraria from Medtronic Vascular, Abbott Vascular, Biotronik, Merck, and Boston Scientific.

NEW ORLEANS – Introduced to the U.S. market in 2008 as an upgraded alternative to the intra-arterial balloon pump, the Impella 2.5 showed clear signs of better performance in high-risk patients undergoing percutaneous coronary intervention in a multicenter, randomized trial with 447 patients.

But once Impella 2.5 entered the U.S. market, enrollment into the study slowed dramatically. Eventually, researchers stopped the trial substantially short of its enrollment target, and the pivotal study's primary end point did not show a statistically significant benefit for Impella 2.5.

The trial also ran into a second problem with a major confounding issue: Interventional cardiologists used rotational atherectomy more aggressively in Impella-treated patients. They seemingly were emboldened by the added cardiac support, and Impella-treated patients had an unbalanced rate of adverse effects.

Despite these problems, the trial results showed a role for the Impella device in high-risk, low-cardiac-output patients undergoing PCI, Dr. William O'Neill said at the meeting

“This device produces superb hemodynamic support during high-risk interventions. It really allows a more complete procedure that leads to fewer late events,” explained Dr. O'Neill, an interventional cardiologist and executive dean for clinical affairs at the University of Miami.

“With these [high-risk] patients, we skate rapidly over thin ice. This device allows us the luxury of taking more time and doing a more complete and safer procedure. I think [that capability] will translate into increased use [of the device] in these high-risk patients,” he added.

Experts who heard the trial results were split on their interpretation of the findings.

“This was a negative study. What is driving the differences you see? I don't understand how to reconcile the results with your conclusion to go ahead [with using] this device,” commented Dr. Ron Waksman, director of experimental angioplasty at Washington (D.C.) Hospital Center.

But Dr. Roxanna Mehran gave the findings a much more positive spin (see box, below right).

PROTECT II was a prospective, multicenter, randomized, controlled trial of the Impella Recover LP 2.5 system vs. IABP (intra-aortic balloon pump) in patients undergoing nonemergent, high-risk PCI. The trial began in November 2007 at 67 U.S. sites, 4 sites in Canada, and 1 site in the Netherlands. It enrolled patients with either unprotected left main coronary disease and a left ventricular ejection fraction of 35% or less, or patients with triple-vessel coronary disease and an ejection fraction of 30% or less.

The primary end point was the 30-day rate of death, MI, stroke, need for repeat revascularization, need for cardiovascular surgery or vascular surgery for limb ischemia, acute renal dysfunction, increased aortic insufficiency, severe hypotension, need for cardiopulmonary resuscitation, ventricular tachycardia, or failure to reopen the target coronaries by PCI.

The patients averaged 67 years old, 80% were men, and 56% had New York Heart Association class III or IV heart failure. Their average Society of Thoracic Surgeons (STS) mortality score was 6, their average SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score was 30, and 63% were considered ineligible for surgery. “The population was “extraordinarily high risk, the most complex patients ever enrolled in a multicenter, randomized, controlled trial,” Dr. O'Neill said.

There were 447 patients enrolled in PROTECT II before the study's data and safety monitoring board stopped the trial last December citing “futility” on the primary end point. This number was 70% of the number of patients originally identified as needed to produce a statistically significant result for the primary end point. Enrollment into the study sharply slowed once the Impella device came onto the U.S. market in June 2008.

During PCI, the participating operators generally managed the Impella patients more aggressively. Heparin was given to 94% in the Impella arm and to 82% in the IABP control arm. Rotational atherectomy was performed in 15% of the Impella patients and in 10% of patients in the IABP arm, a statistically significant difference. Also, participating operators used atherectomy more aggressively in the Impella patients, with an average of five atherectomy passes per patient, compared with two passes in the IABP patients.

Although this shift in treatment approach may have ultimately benefited some of the Impella patients, it also “increased the major adverse event rate and confounded the analysis,” Dr. O'Neill said. “About 70% of patients treated with atherectomy in the Impella group had an adverse event” – primarily rises in the level of creatine kinase–myoglobin – “compared with about 35% treated with atherectomy in the IABP group,” he said in an interview. “It was a procedural imbalance that was hard to control for” in the safety and efficacy analysis.

There was no statistically significant difference for the study's primary outcome, the combined major adverse event rate in the intention-to-treat analysis at 30 days after treatment, as well as at 90 days after treatment. However, at both time points, patients in the Impella arm showed trends toward lower major adverse events rates. At 30 days, the Impella patients had a 36% rate, compared with a 40% rate in the IABP patients. At 90 days, the rates reached 41% and 50%, respectively.

In the per-protocol analysis, at 30 days the Impella patients had a major adverse event rate of 35%, compared with 43% in the IABP patients, which was not a statistically significant difference. At 90 days, the rates reached 41% and 51%, respectively, a difference that was statistically significant.

Dr. O'Neill addressed concerns that the major adverse event measure included many elements of sharply differing clinical importance. “What drove the difference [between the two study arms] was death, myocardial infarction, and need for urgent revascularization – not the small stuff. The real major adverse cardiac events were significantly better” when the Impella device was used, he said in an interview.

An analysis of several prespecified subgroups also highlighted certain types of patients who had significant benefit from the Impella device for the study's primary end point. Among the 88% of patients in the study who were not treated with rotational atherectomy, the 30-day major adverse event rate reached 30%, compared with 42% in the IABP patients, a statistically significant difference. A significant difference in the primary outcome in favor of the Impella patients also occurred in the subgroup that had an STS mortality score lower than 10.

The results also showed a strong trend toward a better primary outcome in the Impella-treated patients when the analysis excluded the first Impella-treated patient for each operator, a finding that highlighted an important learning curve in using the device, Dr. O'Neill said.

Analysis also showed that the 90-day rate of major adverse events in the Impella patients fell from 48% in 2008 to 39% in 2009 and to 37% in 2010. In contrast, the rate in the IABP patients stayed fairly constant (at 47%-52%) in all 3 years, again highlighting the role of experience with the Impella device in achieving better patient outcomes, he said.

“I think many clinicians will see [from these data] that Impella provides a lot of safety,” Dr. O'Neill said.

View on the News

Device Useful for Selected Patients

The results that Dr. O'Neill presented support the use of the Impella 2.5 device in certain clinical situations, specifically in extremely high-risk patients who have a low left ventricular ejection fraction and need protection when undergoing multivessel PCI. Having access to this type of adjunctive device is important, especially for high-risk patients. I can see myself using this device in patients similar to those enrolled in PROTECT II.

It's unfortunate that the trial did not give a definitive answer to the questions posed in the study. The trial was designed as a superiority trial and did not meet its primary end point. The results do not give us a scientific answer on when to use the device because the study stopped early. But studies like this can inform us tremendously on how to manage very high-risk patients. It's a tremendous effort to undertake the study and find the patients who would benefit from this device.

We saw in the results that physicians who used the Impella device had the confidence to more aggressively use atherectomy. That can't be proved, but it appears to be so. The higher use of rotational atherectomy resulted in more creatine kinase–myoglobin elevations in that arm, but the Impella group had fewer critically important MIs (defined as a CK-MB rise of more than eight times the upper limit of normal).

ROXANA MEHRAN, M.D., is professor of medicine and director of interventional cardiovascular research at Mount Sinai Medical Center in New York. She has been a consultant to or received honoraria from Cardiva, Ortho-McNeil, Regado, the Medicines Company, Abbott Vascular, AstraZeneca, and Cordis. She has received research grants from Bristol-Myers Squibb and Sanofi-Aventis.

Vitals

Major Finding: High-risk patients who were aided during PCI with an LVAD (Impella 2.5) had a 41% rate of major adverse events at 90 days, significantly better than the 51% rate in patients treated with a standard intra-aortic balloon pump. But in the intention-to-treat analysis, outcomes did not differ for the two groups at either 30 days or 90 days.

Data Source: PROTECT II, a randomized trial comparing LV support with the Impella 2.5 device and an intra-aortic balloon pump in 447 patients who were treated at 72 sites worldwide.

Disclosures: PROTECT II was funded by Abiomed, which markets the Impella device. Dr. O'Neill has been a consultant to Medtronic. Dr. Waksman has been a consultant to or received honoraria from Medtronic Vascular, Abbott Vascular, Biotronik, Merck, and Boston Scientific.

NEW ORLEANS – Introduced to the U.S. market in 2008 as an upgraded alternative to the intra-arterial balloon pump, the Impella 2.5 showed clear signs of better performance in high-risk patients undergoing percutaneous coronary intervention in a multicenter, randomized trial with 447 patients.

But once Impella 2.5 entered the U.S. market, enrollment into the study slowed dramatically. Eventually, researchers stopped the trial substantially short of its enrollment target, and the pivotal study's primary end point did not show a statistically significant benefit for Impella 2.5.

The trial also ran into a second problem with a major confounding issue: Interventional cardiologists used rotational atherectomy more aggressively in Impella-treated patients. They seemingly were emboldened by the added cardiac support, and Impella-treated patients had an unbalanced rate of adverse effects.

Despite these problems, the trial results showed a role for the Impella device in high-risk, low-cardiac-output patients undergoing PCI, Dr. William O'Neill said at the meeting

“This device produces superb hemodynamic support during high-risk interventions. It really allows a more complete procedure that leads to fewer late events,” explained Dr. O'Neill, an interventional cardiologist and executive dean for clinical affairs at the University of Miami.

“With these [high-risk] patients, we skate rapidly over thin ice. This device allows us the luxury of taking more time and doing a more complete and safer procedure. I think [that capability] will translate into increased use [of the device] in these high-risk patients,” he added.

Experts who heard the trial results were split on their interpretation of the findings.

“This was a negative study. What is driving the differences you see? I don't understand how to reconcile the results with your conclusion to go ahead [with using] this device,” commented Dr. Ron Waksman, director of experimental angioplasty at Washington (D.C.) Hospital Center.

But Dr. Roxanna Mehran gave the findings a much more positive spin (see box, below right).

PROTECT II was a prospective, multicenter, randomized, controlled trial of the Impella Recover LP 2.5 system vs. IABP (intra-aortic balloon pump) in patients undergoing nonemergent, high-risk PCI. The trial began in November 2007 at 67 U.S. sites, 4 sites in Canada, and 1 site in the Netherlands. It enrolled patients with either unprotected left main coronary disease and a left ventricular ejection fraction of 35% or less, or patients with triple-vessel coronary disease and an ejection fraction of 30% or less.

The primary end point was the 30-day rate of death, MI, stroke, need for repeat revascularization, need for cardiovascular surgery or vascular surgery for limb ischemia, acute renal dysfunction, increased aortic insufficiency, severe hypotension, need for cardiopulmonary resuscitation, ventricular tachycardia, or failure to reopen the target coronaries by PCI.

The patients averaged 67 years old, 80% were men, and 56% had New York Heart Association class III or IV heart failure. Their average Society of Thoracic Surgeons (STS) mortality score was 6, their average SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score was 30, and 63% were considered ineligible for surgery. “The population was “extraordinarily high risk, the most complex patients ever enrolled in a multicenter, randomized, controlled trial,” Dr. O'Neill said.

There were 447 patients enrolled in PROTECT II before the study's data and safety monitoring board stopped the trial last December citing “futility” on the primary end point. This number was 70% of the number of patients originally identified as needed to produce a statistically significant result for the primary end point. Enrollment into the study sharply slowed once the Impella device came onto the U.S. market in June 2008.

During PCI, the participating operators generally managed the Impella patients more aggressively. Heparin was given to 94% in the Impella arm and to 82% in the IABP control arm. Rotational atherectomy was performed in 15% of the Impella patients and in 10% of patients in the IABP arm, a statistically significant difference. Also, participating operators used atherectomy more aggressively in the Impella patients, with an average of five atherectomy passes per patient, compared with two passes in the IABP patients.

Although this shift in treatment approach may have ultimately benefited some of the Impella patients, it also “increased the major adverse event rate and confounded the analysis,” Dr. O'Neill said. “About 70% of patients treated with atherectomy in the Impella group had an adverse event” – primarily rises in the level of creatine kinase–myoglobin – “compared with about 35% treated with atherectomy in the IABP group,” he said in an interview. “It was a procedural imbalance that was hard to control for” in the safety and efficacy analysis.

There was no statistically significant difference for the study's primary outcome, the combined major adverse event rate in the intention-to-treat analysis at 30 days after treatment, as well as at 90 days after treatment. However, at both time points, patients in the Impella arm showed trends toward lower major adverse events rates. At 30 days, the Impella patients had a 36% rate, compared with a 40% rate in the IABP patients. At 90 days, the rates reached 41% and 50%, respectively.

In the per-protocol analysis, at 30 days the Impella patients had a major adverse event rate of 35%, compared with 43% in the IABP patients, which was not a statistically significant difference. At 90 days, the rates reached 41% and 51%, respectively, a difference that was statistically significant.

Dr. O'Neill addressed concerns that the major adverse event measure included many elements of sharply differing clinical importance. “What drove the difference [between the two study arms] was death, myocardial infarction, and need for urgent revascularization – not the small stuff. The real major adverse cardiac events were significantly better” when the Impella device was used, he said in an interview.

An analysis of several prespecified subgroups also highlighted certain types of patients who had significant benefit from the Impella device for the study's primary end point. Among the 88% of patients in the study who were not treated with rotational atherectomy, the 30-day major adverse event rate reached 30%, compared with 42% in the IABP patients, a statistically significant difference. A significant difference in the primary outcome in favor of the Impella patients also occurred in the subgroup that had an STS mortality score lower than 10.

The results also showed a strong trend toward a better primary outcome in the Impella-treated patients when the analysis excluded the first Impella-treated patient for each operator, a finding that highlighted an important learning curve in using the device, Dr. O'Neill said.

Analysis also showed that the 90-day rate of major adverse events in the Impella patients fell from 48% in 2008 to 39% in 2009 and to 37% in 2010. In contrast, the rate in the IABP patients stayed fairly constant (at 47%-52%) in all 3 years, again highlighting the role of experience with the Impella device in achieving better patient outcomes, he said.

“I think many clinicians will see [from these data] that Impella provides a lot of safety,” Dr. O'Neill said.

View on the News

Device Useful for Selected Patients

The results that Dr. O'Neill presented support the use of the Impella 2.5 device in certain clinical situations, specifically in extremely high-risk patients who have a low left ventricular ejection fraction and need protection when undergoing multivessel PCI. Having access to this type of adjunctive device is important, especially for high-risk patients. I can see myself using this device in patients similar to those enrolled in PROTECT II.

It's unfortunate that the trial did not give a definitive answer to the questions posed in the study. The trial was designed as a superiority trial and did not meet its primary end point. The results do not give us a scientific answer on when to use the device because the study stopped early. But studies like this can inform us tremendously on how to manage very high-risk patients. It's a tremendous effort to undertake the study and find the patients who would benefit from this device.

We saw in the results that physicians who used the Impella device had the confidence to more aggressively use atherectomy. That can't be proved, but it appears to be so. The higher use of rotational atherectomy resulted in more creatine kinase–myoglobin elevations in that arm, but the Impella group had fewer critically important MIs (defined as a CK-MB rise of more than eight times the upper limit of normal).

ROXANA MEHRAN, M.D., is professor of medicine and director of interventional cardiovascular research at Mount Sinai Medical Center in New York. She has been a consultant to or received honoraria from Cardiva, Ortho-McNeil, Regado, the Medicines Company, Abbott Vascular, AstraZeneca, and Cordis. She has received research grants from Bristol-Myers Squibb and Sanofi-Aventis.

Vitals

Major Finding: High-risk patients who were aided during PCI with an LVAD (Impella 2.5) had a 41% rate of major adverse events at 90 days, significantly better than the 51% rate in patients treated with a standard intra-aortic balloon pump. But in the intention-to-treat analysis, outcomes did not differ for the two groups at either 30 days or 90 days.

Data Source: PROTECT II, a randomized trial comparing LV support with the Impella 2.5 device and an intra-aortic balloon pump in 447 patients who were treated at 72 sites worldwide.

Disclosures: PROTECT II was funded by Abiomed, which markets the Impella device. Dr. O'Neill has been a consultant to Medtronic. Dr. Waksman has been a consultant to or received honoraria from Medtronic Vascular, Abbott Vascular, Biotronik, Merck, and Boston Scientific.

NEW ORLEANS – Introduced to the U.S. market in 2008 as an upgraded alternative to the intra-arterial balloon pump, the Impella 2.5 showed clear signs of better performance in high-risk patients undergoing percutaneous coronary intervention in a multicenter, randomized trial with 447 patients.

But once Impella 2.5 entered the U.S. market, enrollment into the study slowed dramatically. Eventually, researchers stopped the trial substantially short of its enrollment target, and the pivotal study's primary end point did not show a statistically significant benefit for Impella 2.5.

The trial also ran into a second problem with a major confounding issue: Interventional cardiologists used rotational atherectomy more aggressively in Impella-treated patients. They seemingly were emboldened by the added cardiac support, and Impella-treated patients had an unbalanced rate of adverse effects.

Despite these problems, the trial results showed a role for the Impella device in high-risk, low-cardiac-output patients undergoing PCI, Dr. William O'Neill said at the meeting

“This device produces superb hemodynamic support during high-risk interventions. It really allows a more complete procedure that leads to fewer late events,” explained Dr. O'Neill, an interventional cardiologist and executive dean for clinical affairs at the University of Miami.

“With these [high-risk] patients, we skate rapidly over thin ice. This device allows us the luxury of taking more time and doing a more complete and safer procedure. I think [that capability] will translate into increased use [of the device] in these high-risk patients,” he added.

Experts who heard the trial results were split on their interpretation of the findings.

“This was a negative study. What is driving the differences you see? I don't understand how to reconcile the results with your conclusion to go ahead [with using] this device,” commented Dr. Ron Waksman, director of experimental angioplasty at Washington (D.C.) Hospital Center.

But Dr. Roxanna Mehran gave the findings a much more positive spin (see box, below right).

PROTECT II was a prospective, multicenter, randomized, controlled trial of the Impella Recover LP 2.5 system vs. IABP (intra-aortic balloon pump) in patients undergoing nonemergent, high-risk PCI. The trial began in November 2007 at 67 U.S. sites, 4 sites in Canada, and 1 site in the Netherlands. It enrolled patients with either unprotected left main coronary disease and a left ventricular ejection fraction of 35% or less, or patients with triple-vessel coronary disease and an ejection fraction of 30% or less.

The primary end point was the 30-day rate of death, MI, stroke, need for repeat revascularization, need for cardiovascular surgery or vascular surgery for limb ischemia, acute renal dysfunction, increased aortic insufficiency, severe hypotension, need for cardiopulmonary resuscitation, ventricular tachycardia, or failure to reopen the target coronaries by PCI.

The patients averaged 67 years old, 80% were men, and 56% had New York Heart Association class III or IV heart failure. Their average Society of Thoracic Surgeons (STS) mortality score was 6, their average SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score was 30, and 63% were considered ineligible for surgery. “The population was “extraordinarily high risk, the most complex patients ever enrolled in a multicenter, randomized, controlled trial,” Dr. O'Neill said.

There were 447 patients enrolled in PROTECT II before the study's data and safety monitoring board stopped the trial last December citing “futility” on the primary end point. This number was 70% of the number of patients originally identified as needed to produce a statistically significant result for the primary end point. Enrollment into the study sharply slowed once the Impella device came onto the U.S. market in June 2008.

During PCI, the participating operators generally managed the Impella patients more aggressively. Heparin was given to 94% in the Impella arm and to 82% in the IABP control arm. Rotational atherectomy was performed in 15% of the Impella patients and in 10% of patients in the IABP arm, a statistically significant difference. Also, participating operators used atherectomy more aggressively in the Impella patients, with an average of five atherectomy passes per patient, compared with two passes in the IABP patients.

Although this shift in treatment approach may have ultimately benefited some of the Impella patients, it also “increased the major adverse event rate and confounded the analysis,” Dr. O'Neill said. “About 70% of patients treated with atherectomy in the Impella group had an adverse event” – primarily rises in the level of creatine kinase–myoglobin – “compared with about 35% treated with atherectomy in the IABP group,” he said in an interview. “It was a procedural imbalance that was hard to control for” in the safety and efficacy analysis.

There was no statistically significant difference for the study's primary outcome, the combined major adverse event rate in the intention-to-treat analysis at 30 days after treatment, as well as at 90 days after treatment. However, at both time points, patients in the Impella arm showed trends toward lower major adverse events rates. At 30 days, the Impella patients had a 36% rate, compared with a 40% rate in the IABP patients. At 90 days, the rates reached 41% and 50%, respectively.

In the per-protocol analysis, at 30 days the Impella patients had a major adverse event rate of 35%, compared with 43% in the IABP patients, which was not a statistically significant difference. At 90 days, the rates reached 41% and 51%, respectively, a difference that was statistically significant.

Dr. O'Neill addressed concerns that the major adverse event measure included many elements of sharply differing clinical importance. “What drove the difference [between the two study arms] was death, myocardial infarction, and need for urgent revascularization – not the small stuff. The real major adverse cardiac events were significantly better” when the Impella device was used, he said in an interview.

An analysis of several prespecified subgroups also highlighted certain types of patients who had significant benefit from the Impella device for the study's primary end point. Among the 88% of patients in the study who were not treated with rotational atherectomy, the 30-day major adverse event rate reached 30%, compared with 42% in the IABP patients, a statistically significant difference. A significant difference in the primary outcome in favor of the Impella patients also occurred in the subgroup that had an STS mortality score lower than 10.

The results also showed a strong trend toward a better primary outcome in the Impella-treated patients when the analysis excluded the first Impella-treated patient for each operator, a finding that highlighted an important learning curve in using the device, Dr. O'Neill said.

Analysis also showed that the 90-day rate of major adverse events in the Impella patients fell from 48% in 2008 to 39% in 2009 and to 37% in 2010. In contrast, the rate in the IABP patients stayed fairly constant (at 47%-52%) in all 3 years, again highlighting the role of experience with the Impella device in achieving better patient outcomes, he said.

“I think many clinicians will see [from these data] that Impella provides a lot of safety,” Dr. O'Neill said.

View on the News

Device Useful for Selected Patients

The results that Dr. O'Neill presented support the use of the Impella 2.5 device in certain clinical situations, specifically in extremely high-risk patients who have a low left ventricular ejection fraction and need protection when undergoing multivessel PCI. Having access to this type of adjunctive device is important, especially for high-risk patients. I can see myself using this device in patients similar to those enrolled in PROTECT II.

It's unfortunate that the trial did not give a definitive answer to the questions posed in the study. The trial was designed as a superiority trial and did not meet its primary end point. The results do not give us a scientific answer on when to use the device because the study stopped early. But studies like this can inform us tremendously on how to manage very high-risk patients. It's a tremendous effort to undertake the study and find the patients who would benefit from this device.

We saw in the results that physicians who used the Impella device had the confidence to more aggressively use atherectomy. That can't be proved, but it appears to be so. The higher use of rotational atherectomy resulted in more creatine kinase–myoglobin elevations in that arm, but the Impella group had fewer critically important MIs (defined as a CK-MB rise of more than eight times the upper limit of normal).

ROXANA MEHRAN, M.D., is professor of medicine and director of interventional cardiovascular research at Mount Sinai Medical Center in New York. She has been a consultant to or received honoraria from Cardiva, Ortho-McNeil, Regado, the Medicines Company, Abbott Vascular, AstraZeneca, and Cordis. She has received research grants from Bristol-Myers Squibb and Sanofi-Aventis.

Vitals

PHILADELPHIA – Eliminating HLA-B matching from the U.S. priority-points formula that was used for allocating deceased-donor kidneys partially eliminated the allocation disparity against black recipients, but a residual disparity remained, based on an analysis of more than 57,000 U.S. kidney transplants during 2000-2009.

Removal of HLA-B matching from the allocation criteria cut the amount of disparity in organs received by black patients, compared with white patients, by a relative 23%, but during 2006-2009 blacks received deceased-donor kidneys at a rate that was 19% below the rate of kidneys that went to white patients, Dr. Erin C. Hall said at the American Transplant Congress, which was sponsored by the American Society of Transplant Surgeons.

In May 2003, the U.S. Organ Procurement and Transplantation Network – the deceased-donor organ distribution network established by the federal government and administered by the United Network for Organ Sharing (UNOS) – eliminated HLA-B matching as an allocation criterion.

Factors that may explain the residual disparity remain unidentified. Future studies could focus on an examination of center-by-center allocation differences by race in an effort to identify other sources for the disparity, said Dr. Hall, a researcher in the transplant surgery division at Johns Hopkins Hospital in Baltimore.

Before May 2003, U.S. kidney allocation procedures gave priority to recipients who matched for more of the six HLA loci, a policy that improved transplantation outcomes but decreased the number of nonwhite recipients who received organs (N. Engl. J. Med. 2004;350:545-51).

To investigate the impact of this change, Dr. Hall and her associated reviewed UNOS records for the 12,956 kidney transplants that were done during 2000–May 2003 using deceased-donor organs, and for the 44,704 transplants done during May 2003–2009. During the two periods, the level of black patients who were registered with UNOS to await kidney transplants held very steady, accounting for 44% all of listed patients before the criterion change, and for 45% after the change.

During 2000-2003, black patients received deceased-donor kidney transplants at 38% below the rate of white patients, according to a multivariate analysis that adjusted for patient differences in age, sex, primary renal disease cause, dialysis modality, use of preemptive transplant, insurance status, education, panel-reactive antibody level over time, and blood type. During 2003-2009, the transplantation rate among black patients was 23% less than it was in white patients. To allow for equilibration in transplant rates following the 2003 criterion change, Dr. Hall also analyzed transplantation rates during 2006-2009. During this period, the rate in black patients lagged 19% behind the rate in white patients, she reported. All three between-group differences were statistically significant. The amount of change between the 38% disparity rate during 2000-2003 and the 23% disparity rate during 2003-2009 constituted a 23% relative decline in the disparity rate.

Dr. Hall said that she had no relevant financial disclosures.

PHILADELPHIA – Eliminating HLA-B matching from the U.S. priority-points formula that was used for allocating deceased-donor kidneys partially eliminated the allocation disparity against black recipients, but a residual disparity remained, based on an analysis of more than 57,000 U.S. kidney transplants during 2000-2009.

Removal of HLA-B matching from the allocation criteria cut the amount of disparity in organs received by black patients, compared with white patients, by a relative 23%, but during 2006-2009 blacks received deceased-donor kidneys at a rate that was 19% below the rate of kidneys that went to white patients, Dr. Erin C. Hall said at the American Transplant Congress, which was sponsored by the American Society of Transplant Surgeons.

In May 2003, the U.S. Organ Procurement and Transplantation Network – the deceased-donor organ distribution network established by the federal government and administered by the United Network for Organ Sharing (UNOS) – eliminated HLA-B matching as an allocation criterion.

Factors that may explain the residual disparity remain unidentified. Future studies could focus on an examination of center-by-center allocation differences by race in an effort to identify other sources for the disparity, said Dr. Hall, a researcher in the transplant surgery division at Johns Hopkins Hospital in Baltimore.

Before May 2003, U.S. kidney allocation procedures gave priority to recipients who matched for more of the six HLA loci, a policy that improved transplantation outcomes but decreased the number of nonwhite recipients who received organs (N. Engl. J. Med. 2004;350:545-51).

To investigate the impact of this change, Dr. Hall and her associated reviewed UNOS records for the 12,956 kidney transplants that were done during 2000–May 2003 using deceased-donor organs, and for the 44,704 transplants done during May 2003–2009. During the two periods, the level of black patients who were registered with UNOS to await kidney transplants held very steady, accounting for 44% all of listed patients before the criterion change, and for 45% after the change.

During 2000-2003, black patients received deceased-donor kidney transplants at 38% below the rate of white patients, according to a multivariate analysis that adjusted for patient differences in age, sex, primary renal disease cause, dialysis modality, use of preemptive transplant, insurance status, education, panel-reactive antibody level over time, and blood type. During 2003-2009, the transplantation rate among black patients was 23% less than it was in white patients. To allow for equilibration in transplant rates following the 2003 criterion change, Dr. Hall also analyzed transplantation rates during 2006-2009. During this period, the rate in black patients lagged 19% behind the rate in white patients, she reported. All three between-group differences were statistically significant. The amount of change between the 38% disparity rate during 2000-2003 and the 23% disparity rate during 2003-2009 constituted a 23% relative decline in the disparity rate.

Dr. Hall said that she had no relevant financial disclosures.

PHILADELPHIA – Eliminating HLA-B matching from the U.S. priority-points formula that was used for allocating deceased-donor kidneys partially eliminated the allocation disparity against black recipients, but a residual disparity remained, based on an analysis of more than 57,000 U.S. kidney transplants during 2000-2009.

Removal of HLA-B matching from the allocation criteria cut the amount of disparity in organs received by black patients, compared with white patients, by a relative 23%, but during 2006-2009 blacks received deceased-donor kidneys at a rate that was 19% below the rate of kidneys that went to white patients, Dr. Erin C. Hall said at the American Transplant Congress, which was sponsored by the American Society of Transplant Surgeons.

In May 2003, the U.S. Organ Procurement and Transplantation Network – the deceased-donor organ distribution network established by the federal government and administered by the United Network for Organ Sharing (UNOS) – eliminated HLA-B matching as an allocation criterion.

Factors that may explain the residual disparity remain unidentified. Future studies could focus on an examination of center-by-center allocation differences by race in an effort to identify other sources for the disparity, said Dr. Hall, a researcher in the transplant surgery division at Johns Hopkins Hospital in Baltimore.

Before May 2003, U.S. kidney allocation procedures gave priority to recipients who matched for more of the six HLA loci, a policy that improved transplantation outcomes but decreased the number of nonwhite recipients who received organs (N. Engl. J. Med. 2004;350:545-51).

To investigate the impact of this change, Dr. Hall and her associated reviewed UNOS records for the 12,956 kidney transplants that were done during 2000–May 2003 using deceased-donor organs, and for the 44,704 transplants done during May 2003–2009. During the two periods, the level of black patients who were registered with UNOS to await kidney transplants held very steady, accounting for 44% all of listed patients before the criterion change, and for 45% after the change.

During 2000-2003, black patients received deceased-donor kidney transplants at 38% below the rate of white patients, according to a multivariate analysis that adjusted for patient differences in age, sex, primary renal disease cause, dialysis modality, use of preemptive transplant, insurance status, education, panel-reactive antibody level over time, and blood type. During 2003-2009, the transplantation rate among black patients was 23% less than it was in white patients. To allow for equilibration in transplant rates following the 2003 criterion change, Dr. Hall also analyzed transplantation rates during 2006-2009. During this period, the rate in black patients lagged 19% behind the rate in white patients, she reported. All three between-group differences were statistically significant. The amount of change between the 38% disparity rate during 2000-2003 and the 23% disparity rate during 2003-2009 constituted a 23% relative decline in the disparity rate.

Dr. Hall said that she had no relevant financial disclosures.

PHILADELPHIA – Eliminating HLA-B matching from the U.S. priority-points formula that was used for allocating deceased-donor kidneys partially eliminated the allocation disparity against black recipients, but a residual disparity remained, based on an analysis of more than 57,000 U.S. kidney transplants during 2000-2009.

Removal of HLA-B matching from the allocation criteria cut the amount of disparity in organs received by black patients, compared with white patients, by a relative 23%, but during 2006-2009 blacks received deceased-donor kidneys at a rate that was 19% below the rate of kidneys that went to white patients, Dr. Erin C. Hall said at the American Transplant Congress, which was sponsored by the American Society of Transplant Surgeons.

In May 2003, the U.S. Organ Procurement and Transplantation Network – the deceased-donor organ distribution network established by the federal government and administered by the United Network for Organ Sharing (UNOS) – eliminated HLA-B matching as an allocation criterion.

Factors that may explain the residual disparity remain unidentified. Future studies could focus on an examination of center-by-center allocation differences by race in an effort to identify other sources for the disparity, said Dr. Hall, a researcher in the transplant surgery division at Johns Hopkins Hospital in Baltimore.

Before May 2003, U.S. kidney allocation procedures gave priority to recipients who matched for more of the six HLA loci, a policy that improved transplantation outcomes but decreased the number of nonwhite recipients who received organs (N. Engl. J. Med. 2004;350:545-51).

To investigate the impact of this change, Dr. Hall and her associated reviewed UNOS records for the 12,956 kidney transplants that were done during 2000–May 2003 using deceased-donor organs, and for the 44,704 transplants done during May 2003–2009. During the two periods, the level of black patients who were registered with UNOS to await kidney transplants held very steady, accounting for 44% all of listed patients before the criterion change, and for 45% after the change.

During 2000-2003, black patients received deceased-donor kidney transplants at 38% below the rate of white patients, according to a multivariate analysis that adjusted for patient differences in age, sex, primary renal disease cause, dialysis modality, use of preemptive transplant, insurance status, education, panel-reactive antibody level over time, and blood type. During 2003-2009, the transplantation rate among black patients was 23% less than it was in white patients. To allow for equilibration in transplant rates following the 2003 criterion change, Dr. Hall also analyzed transplantation rates during 2006-2009. During this period, the rate in black patients lagged 19% behind the rate in white patients, she reported. All three between-group differences were statistically significant. The amount of change between the 38% disparity rate during 2000-2003 and the 23% disparity rate during 2003-2009 constituted a 23% relative decline in the disparity rate.

Dr. Hall said that she had no relevant financial disclosures.

PHILADELPHIA – Eliminating HLA-B matching from the U.S. priority-points formula that was used for allocating deceased-donor kidneys partially eliminated the allocation disparity against black recipients, but a residual disparity remained, based on an analysis of more than 57,000 U.S. kidney transplants during 2000-2009.

Removal of HLA-B matching from the allocation criteria cut the amount of disparity in organs received by black patients, compared with white patients, by a relative 23%, but during 2006-2009 blacks received deceased-donor kidneys at a rate that was 19% below the rate of kidneys that went to white patients, Dr. Erin C. Hall said at the American Transplant Congress, which was sponsored by the American Society of Transplant Surgeons.

In May 2003, the U.S. Organ Procurement and Transplantation Network – the deceased-donor organ distribution network established by the federal government and administered by the United Network for Organ Sharing (UNOS) – eliminated HLA-B matching as an allocation criterion.

Factors that may explain the residual disparity remain unidentified. Future studies could focus on an examination of center-by-center allocation differences by race in an effort to identify other sources for the disparity, said Dr. Hall, a researcher in the transplant surgery division at Johns Hopkins Hospital in Baltimore.

Before May 2003, U.S. kidney allocation procedures gave priority to recipients who matched for more of the six HLA loci, a policy that improved transplantation outcomes but decreased the number of nonwhite recipients who received organs (N. Engl. J. Med. 2004;350:545-51).

To investigate the impact of this change, Dr. Hall and her associated reviewed UNOS records for the 12,956 kidney transplants that were done during 2000–May 2003 using deceased-donor organs, and for the 44,704 transplants done during May 2003–2009. During the two periods, the level of black patients who were registered with UNOS to await kidney transplants held very steady, accounting for 44% all of listed patients before the criterion change, and for 45% after the change.

During 2000-2003, black patients received deceased-donor kidney transplants at 38% below the rate of white patients, according to a multivariate analysis that adjusted for patient differences in age, sex, primary renal disease cause, dialysis modality, use of preemptive transplant, insurance status, education, panel-reactive antibody level over time, and blood type. During 2003-2009, the transplantation rate among black patients was 23% less than it was in white patients. To allow for equilibration in transplant rates following the 2003 criterion change, Dr. Hall also analyzed transplantation rates during 2006-2009. During this period, the rate in black patients lagged 19% behind the rate in white patients, she reported. All three between-group differences were statistically significant. The amount of change between the 38% disparity rate during 2000-2003 and the 23% disparity rate during 2003-2009 constituted a 23% relative decline in the disparity rate.

Dr. Hall said that she had no relevant financial disclosures.

PHILADELPHIA – Eliminating HLA-B matching from the U.S. priority-points formula that was used for allocating deceased-donor kidneys partially eliminated the allocation disparity against black recipients, but a residual disparity remained, based on an analysis of more than 57,000 U.S. kidney transplants during 2000-2009.

Removal of HLA-B matching from the allocation criteria cut the amount of disparity in organs received by black patients, compared with white patients, by a relative 23%, but during 2006-2009 blacks received deceased-donor kidneys at a rate that was 19% below the rate of kidneys that went to white patients, Dr. Erin C. Hall said at the American Transplant Congress, which was sponsored by the American Society of Transplant Surgeons.

In May 2003, the U.S. Organ Procurement and Transplantation Network – the deceased-donor organ distribution network established by the federal government and administered by the United Network for Organ Sharing (UNOS) – eliminated HLA-B matching as an allocation criterion.

Factors that may explain the residual disparity remain unidentified. Future studies could focus on an examination of center-by-center allocation differences by race in an effort to identify other sources for the disparity, said Dr. Hall, a researcher in the transplant surgery division at Johns Hopkins Hospital in Baltimore.

Before May 2003, U.S. kidney allocation procedures gave priority to recipients who matched for more of the six HLA loci, a policy that improved transplantation outcomes but decreased the number of nonwhite recipients who received organs (N. Engl. J. Med. 2004;350:545-51).

To investigate the impact of this change, Dr. Hall and her associated reviewed UNOS records for the 12,956 kidney transplants that were done during 2000–May 2003 using deceased-donor organs, and for the 44,704 transplants done during May 2003–2009. During the two periods, the level of black patients who were registered with UNOS to await kidney transplants held very steady, accounting for 44% all of listed patients before the criterion change, and for 45% after the change.

During 2000-2003, black patients received deceased-donor kidney transplants at 38% below the rate of white patients, according to a multivariate analysis that adjusted for patient differences in age, sex, primary renal disease cause, dialysis modality, use of preemptive transplant, insurance status, education, panel-reactive antibody level over time, and blood type. During 2003-2009, the transplantation rate among black patients was 23% less than it was in white patients. To allow for equilibration in transplant rates following the 2003 criterion change, Dr. Hall also analyzed transplantation rates during 2006-2009. During this period, the rate in black patients lagged 19% behind the rate in white patients, she reported. All three between-group differences were statistically significant. The amount of change between the 38% disparity rate during 2000-2003 and the 23% disparity rate during 2003-2009 constituted a 23% relative decline in the disparity rate.

Dr. Hall said that she had no relevant financial disclosures.

PHILADELPHIA – Selected U.S. organ donors should undergo testing for infection by Trypanosoma cruzi, the etiologic agent of Chagas’ disease, before organs are taken for transplantation, recommended an expert panel initiated by the United Network for Organ Sharing.

U.S. blood donations already undergo routine screening for T. cruzi, Dr. Peter V. Chin-Hong said at the American Transplant Congress, which was sponsored by the American Society of Transplant Surgeons. As of early 2011, infectious disease experts estimate that about 300,000 Americans were infected with T. cruzi, and the panel learned of about 30 confirmed cases of T. cruzi transmission from infected donors to U.S. organ recipients, he added.

Dr. Chin-Hong and his fellow panel members also recommended that when an organ donor – either living or deceased – is positive for T. cruzi infection, most organs are still usable for transplant as long as the recipient gives informed consent, is closely monitored for 6 months for signs of infection, and is treated promptly with an appropriate drug regimen if infection starts. The panel’s only exception to this policy was a recommendation that hearts from organ donors that are infected with T. cruzi not be used at all because the pathogen specifically targets the myocardium, and hearts that harbor T. cruzi risk eventually developing cardiomyopathy.

The panel backed an aggressive approach to the use of organs from infected donors because "we were concerned that people were discarding these organs "needlessly," Dr. Chin-Hong said in an interview. He estimated that patients who received a kidney or liver from a donor infected by T cruzi had about a 20%-30% risk of becoming infected by the pathogen, and even if infection occurred, reliable treatment exists with the primary agent, benznidazole, or with the second-line drug, nifurtimox.

"We have not seen any negative outcomes using T. cruzi treatment," he said.

"We do the same thing, except all our donors are screened for T. cruzi," commented Dr. Roberta Lattes, coordinator of transplant infectious diseases at the Institute of Nephrology in Buenos Aires. The only difference is that in Argentina, every organ donors is screened because T. cruzi is endemic in Mexico and in Central and South American. The U.S. panel suggested that U.S. organ donors undergo selection for screening by first asking if the donor was born in any of those regions.

"There is insufficient evidence for universal screening" in the United States, although individual U.S. organ procurement agencies might decide to apply universal screening to donors based on local T. cruzi epidemiology, said Dr. Chin-Hong, director of the transplant and immunocompromised host infectious diseases program at the University of California, San Francisco.

"We don’t use drug prophylaxis" on recipients of organs from infected donors "because the drugs are very toxic, and transmission is not that high," Dr. Lattes said. "But you must monitor, and at the least sign of infection you have to treat." She also agreed that hearts from T. cruzi–infected donors should not be used for transplants.

Organ donors who were born in Mexico or Central or South American should receive screening by a T. cruzi test that is approved by the Food and Drug Administration. Patients who receive an organ from a positive donor should undergo periodic testing with the same tests, weekly for the first 2 months after transplant, followed by every other week for the third month, and then monthly for another 3 months. Blood specimens should also be drawn and monitored microscopically for T. cruzi at the same times, and even more frequent specimens should be drawn, tested, and examined if organ recipients develop fever or signs of rejection. Confirmed infection must be treated promptly.

The panel published their recommendations in April (Am. J. Transplant. 2011;11:672-80).

The United Network for Organ Sharing is a private, nonprofit organization that manages the nation’s organ transplant system under contract with the federal government.

Dr. Chin-Hong said he had no relevant financial disclosures.

PHILADELPHIA – Selected U.S. organ donors should undergo testing for infection by Trypanosoma cruzi, the etiologic agent of Chagas’ disease, before organs are taken for transplantation, recommended an expert panel initiated by the United Network for Organ Sharing.

U.S. blood donations already undergo routine screening for T. cruzi, Dr. Peter V. Chin-Hong said at the American Transplant Congress, which was sponsored by the American Society of Transplant Surgeons. As of early 2011, infectious disease experts estimate that about 300,000 Americans were infected with T. cruzi, and the panel learned of about 30 confirmed cases of T. cruzi transmission from infected donors to U.S. organ recipients, he added.

Dr. Chin-Hong and his fellow panel members also recommended that when an organ donor – either living or deceased – is positive for T. cruzi infection, most organs are still usable for transplant as long as the recipient gives informed consent, is closely monitored for 6 months for signs of infection, and is treated promptly with an appropriate drug regimen if infection starts. The panel’s only exception to this policy was a recommendation that hearts from organ donors that are infected with T. cruzi not be used at all because the pathogen specifically targets the myocardium, and hearts that harbor T. cruzi risk eventually developing cardiomyopathy.

The panel backed an aggressive approach to the use of organs from infected donors because "we were concerned that people were discarding these organs "needlessly," Dr. Chin-Hong said in an interview. He estimated that patients who received a kidney or liver from a donor infected by T cruzi had about a 20%-30% risk of becoming infected by the pathogen, and even if infection occurred, reliable treatment exists with the primary agent, benznidazole, or with the second-line drug, nifurtimox.

"We have not seen any negative outcomes using T. cruzi treatment," he said.

"We do the same thing, except all our donors are screened for T. cruzi," commented Dr. Roberta Lattes, coordinator of transplant infectious diseases at the Institute of Nephrology in Buenos Aires. The only difference is that in Argentina, every organ donors is screened because T. cruzi is endemic in Mexico and in Central and South American. The U.S. panel suggested that U.S. organ donors undergo selection for screening by first asking if the donor was born in any of those regions.

"There is insufficient evidence for universal screening" in the United States, although individual U.S. organ procurement agencies might decide to apply universal screening to donors based on local T. cruzi epidemiology, said Dr. Chin-Hong, director of the transplant and immunocompromised host infectious diseases program at the University of California, San Francisco.

"We don’t use drug prophylaxis" on recipients of organs from infected donors "because the drugs are very toxic, and transmission is not that high," Dr. Lattes said. "But you must monitor, and at the least sign of infection you have to treat." She also agreed that hearts from T. cruzi–infected donors should not be used for transplants.

Organ donors who were born in Mexico or Central or South American should receive screening by a T. cruzi test that is approved by the Food and Drug Administration. Patients who receive an organ from a positive donor should undergo periodic testing with the same tests, weekly for the first 2 months after transplant, followed by every other week for the third month, and then monthly for another 3 months. Blood specimens should also be drawn and monitored microscopically for T. cruzi at the same times, and even more frequent specimens should be drawn, tested, and examined if organ recipients develop fever or signs of rejection. Confirmed infection must be treated promptly.

The panel published their recommendations in April (Am. J. Transplant. 2011;11:672-80).

The United Network for Organ Sharing is a private, nonprofit organization that manages the nation’s organ transplant system under contract with the federal government.

Dr. Chin-Hong said he had no relevant financial disclosures.

PHILADELPHIA – Selected U.S. organ donors should undergo testing for infection by Trypanosoma cruzi, the etiologic agent of Chagas’ disease, before organs are taken for transplantation, recommended an expert panel initiated by the United Network for Organ Sharing.

U.S. blood donations already undergo routine screening for T. cruzi, Dr. Peter V. Chin-Hong said at the American Transplant Congress, which was sponsored by the American Society of Transplant Surgeons. As of early 2011, infectious disease experts estimate that about 300,000 Americans were infected with T. cruzi, and the panel learned of about 30 confirmed cases of T. cruzi transmission from infected donors to U.S. organ recipients, he added.

Dr. Chin-Hong and his fellow panel members also recommended that when an organ donor – either living or deceased – is positive for T. cruzi infection, most organs are still usable for transplant as long as the recipient gives informed consent, is closely monitored for 6 months for signs of infection, and is treated promptly with an appropriate drug regimen if infection starts. The panel’s only exception to this policy was a recommendation that hearts from organ donors that are infected with T. cruzi not be used at all because the pathogen specifically targets the myocardium, and hearts that harbor T. cruzi risk eventually developing cardiomyopathy.

The panel backed an aggressive approach to the use of organs from infected donors because "we were concerned that people were discarding these organs "needlessly," Dr. Chin-Hong said in an interview. He estimated that patients who received a kidney or liver from a donor infected by T cruzi had about a 20%-30% risk of becoming infected by the pathogen, and even if infection occurred, reliable treatment exists with the primary agent, benznidazole, or with the second-line drug, nifurtimox.

"We have not seen any negative outcomes using T. cruzi treatment," he said.

"We do the same thing, except all our donors are screened for T. cruzi," commented Dr. Roberta Lattes, coordinator of transplant infectious diseases at the Institute of Nephrology in Buenos Aires. The only difference is that in Argentina, every organ donors is screened because T. cruzi is endemic in Mexico and in Central and South American. The U.S. panel suggested that U.S. organ donors undergo selection for screening by first asking if the donor was born in any of those regions.

"There is insufficient evidence for universal screening" in the United States, although individual U.S. organ procurement agencies might decide to apply universal screening to donors based on local T. cruzi epidemiology, said Dr. Chin-Hong, director of the transplant and immunocompromised host infectious diseases program at the University of California, San Francisco.

"We don’t use drug prophylaxis" on recipients of organs from infected donors "because the drugs are very toxic, and transmission is not that high," Dr. Lattes said. "But you must monitor, and at the least sign of infection you have to treat." She also agreed that hearts from T. cruzi–infected donors should not be used for transplants.

Organ donors who were born in Mexico or Central or South American should receive screening by a T. cruzi test that is approved by the Food and Drug Administration. Patients who receive an organ from a positive donor should undergo periodic testing with the same tests, weekly for the first 2 months after transplant, followed by every other week for the third month, and then monthly for another 3 months. Blood specimens should also be drawn and monitored microscopically for T. cruzi at the same times, and even more frequent specimens should be drawn, tested, and examined if organ recipients develop fever or signs of rejection. Confirmed infection must be treated promptly.

The panel published their recommendations in April (Am. J. Transplant. 2011;11:672-80).

The United Network for Organ Sharing is a private, nonprofit organization that manages the nation’s organ transplant system under contract with the federal government.

Dr. Chin-Hong said he had no relevant financial disclosures.

PHILADELPHIA – Blood transfusions can kill surgery patients, a finding that puts the onus on surgeons to administer transfusions only when absolutely necessary, according to Dr. Gaetano Paone.

An analysis of more than 31,000 patients who underwent isolated coronary artery bypass grafting (CABG) surgery in Michigan during January 2006–June 2010 showed that receiving one or more blood transfusions conferred a nearly threefold increased risk of operative mortality, compared with not receiving a transfusion, Dr. Paone reported at the annual meeting of the American Association for Thoracic Surgery.*

The propensity analysis, which controlled for 17 significant clinical and demographic variables, confirms that "patients who get transfusions don’t do as well as those who don’t. I can’t say unequivocably that it’s the blood transfusions that cause these worse outcomes, but this is a reason to – whenever possible – avoid giving blood transfusions," Dr. Paone said in an interview.

"There is great variability in the rates of transfusions across institutions," noted Dr. Paone, a cardiac surgeon at Henry Ford Hospital in Detroit. In some places, the transfusion rates of isolated CABG patients are 15%, and other places have rates of more than 90%. "That suggests it’s quite discretionary."

Surgeons "have different opinions on the necessary blood level, and the appropriate hematocrit level. It’s hard to see an almost fivefold range of differences in transfusion rates and not have that somehow based on individual preferences rather than on science," he added.

Dr. Paone suggested that surgeons who believe that it is often necessary to give transfusions should strive to make it less necessary. "It’s not just on the basis of this study," he noted. "This study looked at the situation from a somewhat different perspective, but it reached the same conclusion as many others."

Dr. Paone and his associates examined data on 31,818 patients who underwent isolated CABG during the study period at any one of the 33 Michigan hospitals that perform cardiac surgery. The data came from records maintained by the Michigan Society of Thoracic and Cardiovascular Surgeons Quality Collaborative.

The researchers calculated the mortality risk faced by each patient using the STS-PROM (Society of Thoracic Surgeons Predicted Risk of Mortality) model, which takes into account 30 preoperative patient variables. They stratified the patients into four risk groups based on their scores, which represent the percent risk for 30-day perioperative mortality (less than 2%, 2%-5%, 6%-10%, and more than 10%). The percentage of study patients in each ascending risk stratum were 69%, 21%, 7%, and 3%, respectively. The analysis also divided patients into the 55% who received transfusions and the 45% who did not receive any blood. Overall operative mortality among the patients studied was 2%.

As expected, operative mortality was higher among patients who received a transfusion (3.3%), compared with those who did not get blood (0.6%) – a statistically significant sixfold difference in death rates.

The analysis also showed that the significant link between increased mortality and transfusion remained fairly constant across all four risk strata in the study, ranging from a twofold increased risk among patients with an STS-PROM score of 2%-5%, to a fourfold increased risk among patients with a score of more than 10%. The researchers found no statistically significant differences in the increased rate of death among the transfusion recipients across the four preoperative risk strata, Dr. Paone said.

In a further analysis aimed at teasing apart the mortality risk from transfusion and the patients’ background mortality risk based on their disease severity, the researchers performed a propensity score analysis that controlled for 17 significant preoperative risk determinants, including age, sex, weight, race, hypertension, smoking status, need for dialysis, and chronic obstructive pulmonary disease. This analysis showed that patients who received a transfusion had a 2.88-fold increased risk for operative death, compared with patients who did not receive a transfusion, Dr. Paone said.

Dr. Paone said that he had no disclosures.

* Correction, 5/26/2011: An earlier version of this story incorrectly identified the name of the American Association for Thoracic Surgery.

PHILADELPHIA – Blood transfusions can kill surgery patients, a finding that puts the onus on surgeons to administer transfusions only when absolutely necessary, according to Dr. Gaetano Paone.

An analysis of more than 31,000 patients who underwent isolated coronary artery bypass grafting (CABG) surgery in Michigan during January 2006–June 2010 showed that receiving one or more blood transfusions conferred a nearly threefold increased risk of operative mortality, compared with not receiving a transfusion, Dr. Paone reported at the annual meeting of the American Association for Thoracic Surgery.*

The propensity analysis, which controlled for 17 significant clinical and demographic variables, confirms that "patients who get transfusions don’t do as well as those who don’t. I can’t say unequivocably that it’s the blood transfusions that cause these worse outcomes, but this is a reason to – whenever possible – avoid giving blood transfusions," Dr. Paone said in an interview.

"There is great variability in the rates of transfusions across institutions," noted Dr. Paone, a cardiac surgeon at Henry Ford Hospital in Detroit. In some places, the transfusion rates of isolated CABG patients are 15%, and other places have rates of more than 90%. "That suggests it’s quite discretionary."

Surgeons "have different opinions on the necessary blood level, and the appropriate hematocrit level. It’s hard to see an almost fivefold range of differences in transfusion rates and not have that somehow based on individual preferences rather than on science," he added.

Dr. Paone suggested that surgeons who believe that it is often necessary to give transfusions should strive to make it less necessary. "It’s not just on the basis of this study," he noted. "This study looked at the situation from a somewhat different perspective, but it reached the same conclusion as many others."

Dr. Paone and his associates examined data on 31,818 patients who underwent isolated CABG during the study period at any one of the 33 Michigan hospitals that perform cardiac surgery. The data came from records maintained by the Michigan Society of Thoracic and Cardiovascular Surgeons Quality Collaborative.

The researchers calculated the mortality risk faced by each patient using the STS-PROM (Society of Thoracic Surgeons Predicted Risk of Mortality) model, which takes into account 30 preoperative patient variables. They stratified the patients into four risk groups based on their scores, which represent the percent risk for 30-day perioperative mortality (less than 2%, 2%-5%, 6%-10%, and more than 10%). The percentage of study patients in each ascending risk stratum were 69%, 21%, 7%, and 3%, respectively. The analysis also divided patients into the 55% who received transfusions and the 45% who did not receive any blood. Overall operative mortality among the patients studied was 2%.

As expected, operative mortality was higher among patients who received a transfusion (3.3%), compared with those who did not get blood (0.6%) – a statistically significant sixfold difference in death rates.

The analysis also showed that the significant link between increased mortality and transfusion remained fairly constant across all four risk strata in the study, ranging from a twofold increased risk among patients with an STS-PROM score of 2%-5%, to a fourfold increased risk among patients with a score of more than 10%. The researchers found no statistically significant differences in the increased rate of death among the transfusion recipients across the four preoperative risk strata, Dr. Paone said.

In a further analysis aimed at teasing apart the mortality risk from transfusion and the patients’ background mortality risk based on their disease severity, the researchers performed a propensity score analysis that controlled for 17 significant preoperative risk determinants, including age, sex, weight, race, hypertension, smoking status, need for dialysis, and chronic obstructive pulmonary disease. This analysis showed that patients who received a transfusion had a 2.88-fold increased risk for operative death, compared with patients who did not receive a transfusion, Dr. Paone said.

Dr. Paone said that he had no disclosures.

* Correction, 5/26/2011: An earlier version of this story incorrectly identified the name of the American Association for Thoracic Surgery.

PHILADELPHIA – Blood transfusions can kill surgery patients, a finding that puts the onus on surgeons to administer transfusions only when absolutely necessary, according to Dr. Gaetano Paone.

An analysis of more than 31,000 patients who underwent isolated coronary artery bypass grafting (CABG) surgery in Michigan during January 2006–June 2010 showed that receiving one or more blood transfusions conferred a nearly threefold increased risk of operative mortality, compared with not receiving a transfusion, Dr. Paone reported at the annual meeting of the American Association for Thoracic Surgery.*

The propensity analysis, which controlled for 17 significant clinical and demographic variables, confirms that "patients who get transfusions don’t do as well as those who don’t. I can’t say unequivocably that it’s the blood transfusions that cause these worse outcomes, but this is a reason to – whenever possible – avoid giving blood transfusions," Dr. Paone said in an interview.

"There is great variability in the rates of transfusions across institutions," noted Dr. Paone, a cardiac surgeon at Henry Ford Hospital in Detroit. In some places, the transfusion rates of isolated CABG patients are 15%, and other places have rates of more than 90%. "That suggests it’s quite discretionary."

Surgeons "have different opinions on the necessary blood level, and the appropriate hematocrit level. It’s hard to see an almost fivefold range of differences in transfusion rates and not have that somehow based on individual preferences rather than on science," he added.

Dr. Paone suggested that surgeons who believe that it is often necessary to give transfusions should strive to make it less necessary. "It’s not just on the basis of this study," he noted. "This study looked at the situation from a somewhat different perspective, but it reached the same conclusion as many others."

Dr. Paone and his associates examined data on 31,818 patients who underwent isolated CABG during the study period at any one of the 33 Michigan hospitals that perform cardiac surgery. The data came from records maintained by the Michigan Society of Thoracic and Cardiovascular Surgeons Quality Collaborative.

The researchers calculated the mortality risk faced by each patient using the STS-PROM (Society of Thoracic Surgeons Predicted Risk of Mortality) model, which takes into account 30 preoperative patient variables. They stratified the patients into four risk groups based on their scores, which represent the percent risk for 30-day perioperative mortality (less than 2%, 2%-5%, 6%-10%, and more than 10%). The percentage of study patients in each ascending risk stratum were 69%, 21%, 7%, and 3%, respectively. The analysis also divided patients into the 55% who received transfusions and the 45% who did not receive any blood. Overall operative mortality among the patients studied was 2%.

As expected, operative mortality was higher among patients who received a transfusion (3.3%), compared with those who did not get blood (0.6%) – a statistically significant sixfold difference in death rates.

The analysis also showed that the significant link between increased mortality and transfusion remained fairly constant across all four risk strata in the study, ranging from a twofold increased risk among patients with an STS-PROM score of 2%-5%, to a fourfold increased risk among patients with a score of more than 10%. The researchers found no statistically significant differences in the increased rate of death among the transfusion recipients across the four preoperative risk strata, Dr. Paone said.

In a further analysis aimed at teasing apart the mortality risk from transfusion and the patients’ background mortality risk based on their disease severity, the researchers performed a propensity score analysis that controlled for 17 significant preoperative risk determinants, including age, sex, weight, race, hypertension, smoking status, need for dialysis, and chronic obstructive pulmonary disease. This analysis showed that patients who received a transfusion had a 2.88-fold increased risk for operative death, compared with patients who did not receive a transfusion, Dr. Paone said.

Dr. Paone said that he had no disclosures.

* Correction, 5/26/2011: An earlier version of this story incorrectly identified the name of the American Association for Thoracic Surgery.

NEW YORK – Management of type 2 diabetes patients has shifted "from one-size-fits-all to recommendations that are more personalized," according to Dr. Patrick J. O’Connor, a family physician and senior clinical investigator at HealthPartners Research Foundation in Minneapolis.

From a risk-management perspective, that means assessing the role of each cardiovascular risk factor in a given patient and identifying which modifiable factor packs the biggest punch and is likely to yield the most benefit when changed, he said.

Cardiovascular events account for about two-thirds of all deaths in patients with type 2 diabetes, and most of a patient’s cardiovascular risk depends on age and sex, two risk factors that resist modification. The question then becomes which modifiable risk factor smoking, hypertension, hyperlipidemia, hemoglobin A_1c level, and aspirin use – warrants initial attention.

The best way to find out is to run a risk-factor engine analysis on each patient. For the analysis, each of the patient’s actual values is run individually through a risk-assessment formula, each time substituting normal values for all the modifiable factors except one. This process helps to identify the modifiable factor that, if normalized, stands to most benefit the patient.

The best known risk-factor formulas are the Framingham Risk Score, and for patients with diabetes the score derived from data in the UK Prospective Diabetes Study (UKPDS). "No risk engines available today are perfect; the epidemiologic data [that the risk scoring formula derives from] may be out of date," he said. But among the risk formulas currently available, "the UKPDS is the most appropriate for patients with diabetes," and includes an entry for hemoglobin A_1c.

Dr. O’Connor and his associates are in the process of producing a new risk-engine website designed for patients with diabetes.

Electronic medical records have made risk-engine assessments easy, because a physician can set up the electronic record to run the engine automatically using a patient’s stored risk-factor data.

For example, the UKPDS risk-scoring formula calculates that a 70-year-old man who doesn’t smoke and has had diabetes for 15 years with a hemoglobin A_1c of 7.2%, a systolic blood pressure of 170 mm Hg, and moderate levels of total cholesterol and high density lipoprotein cholesterol has a 15% risk for a coronary heart disease event and a 21% risk for a stroke over the next 10 years. If his systolic pressure dropped to 140 mm Hg, his coronary event risk would fall to 13%, and his stroke risk would drop to 18% – modest declines.

An analysis like this might suggest that it is not worth the effort of undertaking the treatment required to cut the patient’s systolic pressure by 30 mm Hg to achieve such modest risk improvements.

On the other hand, if the same 70-year-old man also smoked at baseline, his 10-year coronary event risk would be 19% and his stroke risk 30%. It might be worth working with the patient to get him to stop smoking and to treat his systolic hypertension, as both actions would cut his 10-year stroke risk by an absolute value of 10%.

"Use the risk engine to get a sense of what the treatment should be. If the patient has little or no reversible risk, then stop. Not all interventions are of equal benefit to all patients at a given time," Dr. O’Connor noted.

Dr. O’Connor said he had no relevant financial disclosures.

NEW YORK – Management of type 2 diabetes patients has shifted "from one-size-fits-all to recommendations that are more personalized," according to Dr. Patrick J. O’Connor, a family physician and senior clinical investigator at HealthPartners Research Foundation in Minneapolis.

From a risk-management perspective, that means assessing the role of each cardiovascular risk factor in a given patient and identifying which modifiable factor packs the biggest punch and is likely to yield the most benefit when changed, he said.

Cardiovascular events account for about two-thirds of all deaths in patients with type 2 diabetes, and most of a patient’s cardiovascular risk depends on age and sex, two risk factors that resist modification. The question then becomes which modifiable risk factor smoking, hypertension, hyperlipidemia, hemoglobin A_1c level, and aspirin use – warrants initial attention.

The best way to find out is to run a risk-factor engine analysis on each patient. For the analysis, each of the patient’s actual values is run individually through a risk-assessment formula, each time substituting normal values for all the modifiable factors except one. This process helps to identify the modifiable factor that, if normalized, stands to most benefit the patient.

The best known risk-factor formulas are the Framingham Risk Score, and for patients with diabetes the score derived from data in the UK Prospective Diabetes Study (UKPDS). "No risk engines available today are perfect; the epidemiologic data [that the risk scoring formula derives from] may be out of date," he said. But among the risk formulas currently available, "the UKPDS is the most appropriate for patients with diabetes," and includes an entry for hemoglobin A_1c.

Dr. O’Connor and his associates are in the process of producing a new risk-engine website designed for patients with diabetes.

Electronic medical records have made risk-engine assessments easy, because a physician can set up the electronic record to run the engine automatically using a patient’s stored risk-factor data.

For example, the UKPDS risk-scoring formula calculates that a 70-year-old man who doesn’t smoke and has had diabetes for 15 years with a hemoglobin A_1c of 7.2%, a systolic blood pressure of 170 mm Hg, and moderate levels of total cholesterol and high density lipoprotein cholesterol has a 15% risk for a coronary heart disease event and a 21% risk for a stroke over the next 10 years. If his systolic pressure dropped to 140 mm Hg, his coronary event risk would fall to 13%, and his stroke risk would drop to 18% – modest declines.

An analysis like this might suggest that it is not worth the effort of undertaking the treatment required to cut the patient’s systolic pressure by 30 mm Hg to achieve such modest risk improvements.

On the other hand, if the same 70-year-old man also smoked at baseline, his 10-year coronary event risk would be 19% and his stroke risk 30%. It might be worth working with the patient to get him to stop smoking and to treat his systolic hypertension, as both actions would cut his 10-year stroke risk by an absolute value of 10%.

"Use the risk engine to get a sense of what the treatment should be. If the patient has little or no reversible risk, then stop. Not all interventions are of equal benefit to all patients at a given time," Dr. O’Connor noted.

Dr. O’Connor said he had no relevant financial disclosures.

NEW YORK – Management of type 2 diabetes patients has shifted "from one-size-fits-all to recommendations that are more personalized," according to Dr. Patrick J. O’Connor, a family physician and senior clinical investigator at HealthPartners Research Foundation in Minneapolis.

From a risk-management perspective, that means assessing the role of each cardiovascular risk factor in a given patient and identifying which modifiable factor packs the biggest punch and is likely to yield the most benefit when changed, he said.

Cardiovascular events account for about two-thirds of all deaths in patients with type 2 diabetes, and most of a patient’s cardiovascular risk depends on age and sex, two risk factors that resist modification. The question then becomes which modifiable risk factor smoking, hypertension, hyperlipidemia, hemoglobin A_1c level, and aspirin use – warrants initial attention.

The best way to find out is to run a risk-factor engine analysis on each patient. For the analysis, each of the patient’s actual values is run individually through a risk-assessment formula, each time substituting normal values for all the modifiable factors except one. This process helps to identify the modifiable factor that, if normalized, stands to most benefit the patient.

The best known risk-factor formulas are the Framingham Risk Score, and for patients with diabetes the score derived from data in the UK Prospective Diabetes Study (UKPDS). "No risk engines available today are perfect; the epidemiologic data [that the risk scoring formula derives from] may be out of date," he said. But among the risk formulas currently available, "the UKPDS is the most appropriate for patients with diabetes," and includes an entry for hemoglobin A_1c.

Dr. O’Connor and his associates are in the process of producing a new risk-engine website designed for patients with diabetes.

Electronic medical records have made risk-engine assessments easy, because a physician can set up the electronic record to run the engine automatically using a patient’s stored risk-factor data.

For example, the UKPDS risk-scoring formula calculates that a 70-year-old man who doesn’t smoke and has had diabetes for 15 years with a hemoglobin A_1c of 7.2%, a systolic blood pressure of 170 mm Hg, and moderate levels of total cholesterol and high density lipoprotein cholesterol has a 15% risk for a coronary heart disease event and a 21% risk for a stroke over the next 10 years. If his systolic pressure dropped to 140 mm Hg, his coronary event risk would fall to 13%, and his stroke risk would drop to 18% – modest declines.

An analysis like this might suggest that it is not worth the effort of undertaking the treatment required to cut the patient’s systolic pressure by 30 mm Hg to achieve such modest risk improvements.

On the other hand, if the same 70-year-old man also smoked at baseline, his 10-year coronary event risk would be 19% and his stroke risk 30%. It might be worth working with the patient to get him to stop smoking and to treat his systolic hypertension, as both actions would cut his 10-year stroke risk by an absolute value of 10%.

"Use the risk engine to get a sense of what the treatment should be. If the patient has little or no reversible risk, then stop. Not all interventions are of equal benefit to all patients at a given time," Dr. O’Connor noted.

Dr. O’Connor said he had no relevant financial disclosures.

NEW YORK – Management of type 2 diabetes patients has shifted "from one-size-fits-all to recommendations that are more personalized," according to Dr. Patrick J. O’Connor, a family physician and senior clinical investigator at HealthPartners Research Foundation in Minneapolis.

From a risk-management perspective, that means assessing the role of each cardiovascular risk factor in a given patient and identifying which modifiable factor packs the biggest punch and is likely to yield the most benefit when changed, he said.

Cardiovascular events account for about two-thirds of all deaths in patients with type 2 diabetes, and most of a patient’s cardiovascular risk depends on age and sex, two risk factors that resist modification. The question then becomes which modifiable risk factor smoking, hypertension, hyperlipidemia, hemoglobin A_1c level, and aspirin use – warrants initial attention.

The best way to find out is to run a risk-factor engine analysis on each patient. For the analysis, each of the patient’s actual values is run individually through a risk-assessment formula, each time substituting normal values for all the modifiable factors except one. This process helps to identify the modifiable factor that, if normalized, stands to most benefit the patient.

The best known risk-factor formulas are the Framingham Risk Score, and for patients with diabetes the score derived from data in the UK Prospective Diabetes Study (UKPDS). "No risk engines available today are perfect; the epidemiologic data [that the risk scoring formula derives from] may be out of date," he said. But among the risk formulas currently available, "the UKPDS is the most appropriate for patients with diabetes," and includes an entry for hemoglobin A_1c.

Dr. O’Connor and his associates are in the process of producing a new risk-engine website designed for patients with diabetes.

Electronic medical records have made risk-engine assessments easy, because a physician can set up the electronic record to run the engine automatically using a patient’s stored risk-factor data.

For example, the UKPDS risk-scoring formula calculates that a 70-year-old man who doesn’t smoke and has had diabetes for 15 years with a hemoglobin A_1c of 7.2%, a systolic blood pressure of 170 mm Hg, and moderate levels of total cholesterol and high density lipoprotein cholesterol has a 15% risk for a coronary heart disease event and a 21% risk for a stroke over the next 10 years. If his systolic pressure dropped to 140 mm Hg, his coronary event risk would fall to 13%, and his stroke risk would drop to 18% – modest declines.

An analysis like this might suggest that it is not worth the effort of undertaking the treatment required to cut the patient’s systolic pressure by 30 mm Hg to achieve such modest risk improvements.

On the other hand, if the same 70-year-old man also smoked at baseline, his 10-year coronary event risk would be 19% and his stroke risk 30%. It might be worth working with the patient to get him to stop smoking and to treat his systolic hypertension, as both actions would cut his 10-year stroke risk by an absolute value of 10%.

"Use the risk engine to get a sense of what the treatment should be. If the patient has little or no reversible risk, then stop. Not all interventions are of equal benefit to all patients at a given time," Dr. O’Connor noted.

Dr. O’Connor said he had no relevant financial disclosures.

NEW YORK – Management of type 2 diabetes patients has shifted "from one-size-fits-all to recommendations that are more personalized," according to Dr. Patrick J. O’Connor, a family physician and senior clinical investigator at HealthPartners Research Foundation in Minneapolis.

From a risk-management perspective, that means assessing the role of each cardiovascular risk factor in a given patient and identifying which modifiable factor packs the biggest punch and is likely to yield the most benefit when changed, he said.

Cardiovascular events account for about two-thirds of all deaths in patients with type 2 diabetes, and most of a patient’s cardiovascular risk depends on age and sex, two risk factors that resist modification. The question then becomes which modifiable risk factor smoking, hypertension, hyperlipidemia, hemoglobin A_1c level, and aspirin use – warrants initial attention.

The best way to find out is to run a risk-factor engine analysis on each patient. For the analysis, each of the patient’s actual values is run individually through a risk-assessment formula, each time substituting normal values for all the modifiable factors except one. This process helps to identify the modifiable factor that, if normalized, stands to most benefit the patient.

The best known risk-factor formulas are the Framingham Risk Score, and for patients with diabetes the score derived from data in the UK Prospective Diabetes Study (UKPDS). "No risk engines available today are perfect; the epidemiologic data [that the risk scoring formula derives from] may be out of date," he said. But among the risk formulas currently available, "the UKPDS is the most appropriate for patients with diabetes," and includes an entry for hemoglobin A_1c.

Dr. O’Connor and his associates are in the process of producing a new risk-engine website designed for patients with diabetes.

Electronic medical records have made risk-engine assessments easy, because a physician can set up the electronic record to run the engine automatically using a patient’s stored risk-factor data.

For example, the UKPDS risk-scoring formula calculates that a 70-year-old man who doesn’t smoke and has had diabetes for 15 years with a hemoglobin A_1c of 7.2%, a systolic blood pressure of 170 mm Hg, and moderate levels of total cholesterol and high density lipoprotein cholesterol has a 15% risk for a coronary heart disease event and a 21% risk for a stroke over the next 10 years. If his systolic pressure dropped to 140 mm Hg, his coronary event risk would fall to 13%, and his stroke risk would drop to 18% – modest declines.

An analysis like this might suggest that it is not worth the effort of undertaking the treatment required to cut the patient’s systolic pressure by 30 mm Hg to achieve such modest risk improvements.

On the other hand, if the same 70-year-old man also smoked at baseline, his 10-year coronary event risk would be 19% and his stroke risk 30%. It might be worth working with the patient to get him to stop smoking and to treat his systolic hypertension, as both actions would cut his 10-year stroke risk by an absolute value of 10%.

"Use the risk engine to get a sense of what the treatment should be. If the patient has little or no reversible risk, then stop. Not all interventions are of equal benefit to all patients at a given time," Dr. O’Connor noted.

Dr. O’Connor said he had no relevant financial disclosures.

NEW YORK – Management of type 2 diabetes patients has shifted "from one-size-fits-all to recommendations that are more personalized," according to Dr. Patrick J. O’Connor, a family physician and senior clinical investigator at HealthPartners Research Foundation in Minneapolis.

From a risk-management perspective, that means assessing the role of each cardiovascular risk factor in a given patient and identifying which modifiable factor packs the biggest punch and is likely to yield the most benefit when changed, he said.

Cardiovascular events account for about two-thirds of all deaths in patients with type 2 diabetes, and most of a patient’s cardiovascular risk depends on age and sex, two risk factors that resist modification. The question then becomes which modifiable risk factor smoking, hypertension, hyperlipidemia, hemoglobin A_1c level, and aspirin use – warrants initial attention.

The best way to find out is to run a risk-factor engine analysis on each patient. For the analysis, each of the patient’s actual values is run individually through a risk-assessment formula, each time substituting normal values for all the modifiable factors except one. This process helps to identify the modifiable factor that, if normalized, stands to most benefit the patient.

The best known risk-factor formulas are the Framingham Risk Score, and for patients with diabetes the score derived from data in the UK Prospective Diabetes Study (UKPDS). "No risk engines available today are perfect; the epidemiologic data [that the risk scoring formula derives from] may be out of date," he said. But among the risk formulas currently available, "the UKPDS is the most appropriate for patients with diabetes," and includes an entry for hemoglobin A_1c.

Dr. O’Connor and his associates are in the process of producing a new risk-engine website designed for patients with diabetes.

Electronic medical records have made risk-engine assessments easy, because a physician can set up the electronic record to run the engine automatically using a patient’s stored risk-factor data.

For example, the UKPDS risk-scoring formula calculates that a 70-year-old man who doesn’t smoke and has had diabetes for 15 years with a hemoglobin A_1c of 7.2%, a systolic blood pressure of 170 mm Hg, and moderate levels of total cholesterol and high density lipoprotein cholesterol has a 15% risk for a coronary heart disease event and a 21% risk for a stroke over the next 10 years. If his systolic pressure dropped to 140 mm Hg, his coronary event risk would fall to 13%, and his stroke risk would drop to 18% – modest declines.

An analysis like this might suggest that it is not worth the effort of undertaking the treatment required to cut the patient’s systolic pressure by 30 mm Hg to achieve such modest risk improvements.

On the other hand, if the same 70-year-old man also smoked at baseline, his 10-year coronary event risk would be 19% and his stroke risk 30%. It might be worth working with the patient to get him to stop smoking and to treat his systolic hypertension, as both actions would cut his 10-year stroke risk by an absolute value of 10%.

"Use the risk engine to get a sense of what the treatment should be. If the patient has little or no reversible risk, then stop. Not all interventions are of equal benefit to all patients at a given time," Dr. O’Connor noted.

Dr. O’Connor said he had no relevant financial disclosures.

NEW YORK – Management of type 2 diabetes patients has shifted "from one-size-fits-all to recommendations that are more personalized," according to Dr. Patrick J. O’Connor, a family physician and senior clinical investigator at HealthPartners Research Foundation in Minneapolis.

From a risk-management perspective, that means assessing the role of each cardiovascular risk factor in a given patient and identifying which modifiable factor packs the biggest punch and is likely to yield the most benefit when changed, he said.

Cardiovascular events account for about two-thirds of all deaths in patients with type 2 diabetes, and most of a patient’s cardiovascular risk depends on age and sex, two risk factors that resist modification. The question then becomes which modifiable risk factor smoking, hypertension, hyperlipidemia, hemoglobin A_1c level, and aspirin use – warrants initial attention.

The best way to find out is to run a risk-factor engine analysis on each patient. For the analysis, each of the patient’s actual values is run individually through a risk-assessment formula, each time substituting normal values for all the modifiable factors except one. This process helps to identify the modifiable factor that, if normalized, stands to most benefit the patient.

The best known risk-factor formulas are the Framingham Risk Score, and for patients with diabetes the score derived from data in the UK Prospective Diabetes Study (UKPDS). "No risk engines available today are perfect; the epidemiologic data [that the risk scoring formula derives from] may be out of date," he said. But among the risk formulas currently available, "the UKPDS is the most appropriate for patients with diabetes," and includes an entry for hemoglobin A_1c.

Dr. O’Connor and his associates are in the process of producing a new risk-engine website designed for patients with diabetes.

Electronic medical records have made risk-engine assessments easy, because a physician can set up the electronic record to run the engine automatically using a patient’s stored risk-factor data.

For example, the UKPDS risk-scoring formula calculates that a 70-year-old man who doesn’t smoke and has had diabetes for 15 years with a hemoglobin A_1c of 7.2%, a systolic blood pressure of 170 mm Hg, and moderate levels of total cholesterol and high density lipoprotein cholesterol has a 15% risk for a coronary heart disease event and a 21% risk for a stroke over the next 10 years. If his systolic pressure dropped to 140 mm Hg, his coronary event risk would fall to 13%, and his stroke risk would drop to 18% – modest declines.

An analysis like this might suggest that it is not worth the effort of undertaking the treatment required to cut the patient’s systolic pressure by 30 mm Hg to achieve such modest risk improvements.

On the other hand, if the same 70-year-old man also smoked at baseline, his 10-year coronary event risk would be 19% and his stroke risk 30%. It might be worth working with the patient to get him to stop smoking and to treat his systolic hypertension, as both actions would cut his 10-year stroke risk by an absolute value of 10%.

"Use the risk engine to get a sense of what the treatment should be. If the patient has little or no reversible risk, then stop. Not all interventions are of equal benefit to all patients at a given time," Dr. O’Connor noted.

Dr. O’Connor said he had no relevant financial disclosures.

NEW YORK – Management of type 2 diabetes patients has shifted "from one-size-fits-all to recommendations that are more personalized," according to Dr. Patrick J. O’Connor, a family physician and senior clinical investigator at HealthPartners Research Foundation in Minneapolis.

From a risk-management perspective, that means assessing the role of each cardiovascular risk factor in a given patient and identifying which modifiable factor packs the biggest punch and is likely to yield the most benefit when changed, he said.

Cardiovascular events account for about two-thirds of all deaths in patients with type 2 diabetes, and most of a patient’s cardiovascular risk depends on age and sex, two risk factors that resist modification. The question then becomes which modifiable risk factor smoking, hypertension, hyperlipidemia, hemoglobin A_1c level, and aspirin use – warrants initial attention.

The best way to find out is to run a risk-factor engine analysis on each patient. For the analysis, each of the patient’s actual values is run individually through a risk-assessment formula, each time substituting normal values for all the modifiable factors except one. This process helps to identify the modifiable factor that, if normalized, stands to most benefit the patient.

The best known risk-factor formulas are the Framingham Risk Score, and for patients with diabetes the score derived from data in the UK Prospective Diabetes Study (UKPDS). "No risk engines available today are perfect; the epidemiologic data [that the risk scoring formula derives from] may be out of date," he said. But among the risk formulas currently available, "the UKPDS is the most appropriate for patients with diabetes," and includes an entry for hemoglobin A_1c.

Dr. O’Connor and his associates are in the process of producing a new risk-engine website designed for patients with diabetes.

Electronic medical records have made risk-engine assessments easy, because a physician can set up the electronic record to run the engine automatically using a patient’s stored risk-factor data.

For example, the UKPDS risk-scoring formula calculates that a 70-year-old man who doesn’t smoke and has had diabetes for 15 years with a hemoglobin A_1c of 7.2%, a systolic blood pressure of 170 mm Hg, and moderate levels of total cholesterol and high density lipoprotein cholesterol has a 15% risk for a coronary heart disease event and a 21% risk for a stroke over the next 10 years. If his systolic pressure dropped to 140 mm Hg, his coronary event risk would fall to 13%, and his stroke risk would drop to 18% – modest declines.

An analysis like this might suggest that it is not worth the effort of undertaking the treatment required to cut the patient’s systolic pressure by 30 mm Hg to achieve such modest risk improvements.

On the other hand, if the same 70-year-old man also smoked at baseline, his 10-year coronary event risk would be 19% and his stroke risk 30%. It might be worth working with the patient to get him to stop smoking and to treat his systolic hypertension, as both actions would cut his 10-year stroke risk by an absolute value of 10%.

"Use the risk engine to get a sense of what the treatment should be. If the patient has little or no reversible risk, then stop. Not all interventions are of equal benefit to all patients at a given time," Dr. O’Connor noted.

Dr. O’Connor said he had no relevant financial disclosures.

NEW YORK – Management of type 2 diabetes patients has shifted "from one-size-fits-all to recommendations that are more personalized," according to Dr. Patrick J. O’Connor, a family physician and senior clinical investigator at HealthPartners Research Foundation in Minneapolis.

From a risk-management perspective, that means assessing the role of each cardiovascular risk factor in a given patient and identifying which modifiable factor packs the biggest punch and is likely to yield the most benefit when changed, he said.

Cardiovascular events account for about two-thirds of all deaths in patients with type 2 diabetes, and most of a patient’s cardiovascular risk depends on age and sex, two risk factors that resist modification. The question then becomes which modifiable risk factor smoking, hypertension, hyperlipidemia, hemoglobin A_1c level, and aspirin use – warrants initial attention.

The best way to find out is to run a risk-factor engine analysis on each patient. For the analysis, each of the patient’s actual values is run individually through a risk-assessment formula, each time substituting normal values for all the modifiable factors except one. This process helps to identify the modifiable factor that, if normalized, stands to most benefit the patient.

The best known risk-factor formulas are the Framingham Risk Score, and for patients with diabetes the score derived from data in the UK Prospective Diabetes Study (UKPDS). "No risk engines available today are perfect; the epidemiologic data [that the risk scoring formula derives from] may be out of date," he said. But among the risk formulas currently available, "the UKPDS is the most appropriate for patients with diabetes," and includes an entry for hemoglobin A_1c.

Dr. O’Connor and his associates are in the process of producing a new risk-engine website designed for patients with diabetes.

Electronic medical records have made risk-engine assessments easy, because a physician can set up the electronic record to run the engine automatically using a patient’s stored risk-factor data.

For example, the UKPDS risk-scoring formula calculates that a 70-year-old man who doesn’t smoke and has had diabetes for 15 years with a hemoglobin A_1c of 7.2%, a systolic blood pressure of 170 mm Hg, and moderate levels of total cholesterol and high density lipoprotein cholesterol has a 15% risk for a coronary heart disease event and a 21% risk for a stroke over the next 10 years. If his systolic pressure dropped to 140 mm Hg, his coronary event risk would fall to 13%, and his stroke risk would drop to 18% – modest declines.

An analysis like this might suggest that it is not worth the effort of undertaking the treatment required to cut the patient’s systolic pressure by 30 mm Hg to achieve such modest risk improvements.

On the other hand, if the same 70-year-old man also smoked at baseline, his 10-year coronary event risk would be 19% and his stroke risk 30%. It might be worth working with the patient to get him to stop smoking and to treat his systolic hypertension, as both actions would cut his 10-year stroke risk by an absolute value of 10%.

"Use the risk engine to get a sense of what the treatment should be. If the patient has little or no reversible risk, then stop. Not all interventions are of equal benefit to all patients at a given time," Dr. O’Connor noted.

Dr. O’Connor said he had no relevant financial disclosures.

NEW ORLEANS – Nearly half of patients who received an implantable cardioverter defibrillator in Massachusetts during 1998-2008 had at least one clinical factor that categorized them as an off-label recipient, based on the exclusion criteria used in the clinical trials that established the efficacy of these devices.

The most common off-label use occurred in patients aged either 75 or older or 19 or younger, which in both cases put them outside of the age enrollment criteria for the implantable cardioverter defibrillator (ICD) trials, Dr. Norman S. Kato reported while presenting a poster at the annual meeting of the American College of Cardiology.

ICDs given to patients outside the age range that was tested in trials accounted for well over a quarter of all ICD use in Massachusetts during the period studied, and more than half of all off-label use. Other common off-label ICD uses occurred in patients with renal insufficiency or a recent acute MI, reported Dr. Kato, a cardiothoracic surgeon in Encino, Calif., who has consulted with the Food and Drug Administration, and his associates in their poster (J. Am Coll. Cardiol. 2011;57:E184).

Their analysis, which included 15,724 ICD recipients during the 11-year period studied, represents "the first analysis [of ICD use] to encompass all patients who have received this technology in a single state," he said in an interview. But he also cautioned that "it would be incorrect to generalize these results to other states, or to assume anything about practice patterns in Massachusetts" in the years following 2008.

"The key finding from our study was that patients over age 65 represent a significant portion of the population receiving these devices. Our research revealed that about 45% of all patients receiving the devices in the Medicare age group were age 75 or older." In addition, the results showed that 15% of recipients were age 85 or older.

"ICDs may have been implanted when there was little empirical evidence to support their use. Because subjects over age 75 were specifically excluded from the randomized clinical trials [of ICDs,] there is no scientific evidence to support the notion that ICDs are safe or effective in this group," Dr. Kato said. "We really need to conduct randomized clinical trials in the excluded groups to determine safety and efficacy. If there is a lot of off-label use for a specific indication, then it stands to reason that clinical trials should be conducted to determine the safety and efficacy of the device for these specific indications.

"Off-label use does not necessarily mean that the use was without benefit or was unsafe," he noted. "Off-label use is simply the use of the device for conditions that were not tested during the randomized clinical trials."

The Centers for Medicare and Medicaid Services, in a 2005 decision memo on ICD use, noted that only 10% of patients who were enrolled in the two largest ICD trials were aged 75 or older, and as a consequence "the implantation of a defibrillator in the most elderly patients should be carefully considered and not routinely recommended," the memo said (CAG-00157R3).

Dr. Kato’s study of Massachusetts ICD usage also showed disproportionate placement of ICDs in men. During 1998-2008, men received ICDs three- to eightfold more often than did women for primary prevention indications, and three- to ninefold more often for secondary prevention.

These findings raise issues of a sex bias or a disease bias that favored men over women for ICD placement, he said. "In general, men have a higher risk for and greater rates of heart attack and coronary artery disease than women, hence men should probably be more likely to receive an ICD. But this merits consideration since results from other studies have also identified the same frequency differences by gender," said Dr. Kato.

The analyses used data compiled by the Massachusetts Department of Health and Human Services on hospital case mix and charge, as well as population estimates from the National Center for Health Statistics.

During the 11-year period studied, the rate of off-label ICD use for primary prevention indications ranged from 28% to 50%, depending on the year. In 2008, about 45% of Massachusetts patients who received an ICD had at least one off-label clinical feature, with age being an off-label factor for about 28% of all recipients. Primary-prevention use, which totaled 13,801 patients over the 11 years studied, occurred in patients with a diagnosis of heart failure or cardiomyopathy.

In 2008, about 45% of patients who received an ICD for secondary prevention had an off-label feature. Secondary-prevention use, which occurred in a total of 1,923 patients in the 11 years studied, included the indications of a history of cardiac arrest or ventricular arrhythmia during the year prior to ICD placement in patients who did not have a primary-prevention indication.

Criteria that led to exclusion from the ICD efficacy trials and hence constitute markers of off-label use included patients undergoing simultaneous percutaneous coronary intervention or coronary artery bypass surgery, and patients with a recent acute MI, renal failure, liver failure, neurologic failure, solid tumor, or dementia, as well as patients on dialysis, and patients aged 75 or older or aged 19 or younger.

Dr. Kato and his associates on the study said that they had no disclosures.

NEW ORLEANS – Nearly half of patients who received an implantable cardioverter defibrillator in Massachusetts during 1998-2008 had at least one clinical factor that categorized them as an off-label recipient, based on the exclusion criteria used in the clinical trials that established the efficacy of these devices.

The most common off-label use occurred in patients aged either 75 or older or 19 or younger, which in both cases put them outside of the age enrollment criteria for the implantable cardioverter defibrillator (ICD) trials, Dr. Norman S. Kato reported while presenting a poster at the annual meeting of the American College of Cardiology.

ICDs given to patients outside the age range that was tested in trials accounted for well over a quarter of all ICD use in Massachusetts during the period studied, and more than half of all off-label use. Other common off-label ICD uses occurred in patients with renal insufficiency or a recent acute MI, reported Dr. Kato, a cardiothoracic surgeon in Encino, Calif., who has consulted with the Food and Drug Administration, and his associates in their poster (J. Am Coll. Cardiol. 2011;57:E184).

Their analysis, which included 15,724 ICD recipients during the 11-year period studied, represents "the first analysis [of ICD use] to encompass all patients who have received this technology in a single state," he said in an interview. But he also cautioned that "it would be incorrect to generalize these results to other states, or to assume anything about practice patterns in Massachusetts" in the years following 2008.

"The key finding from our study was that patients over age 65 represent a significant portion of the population receiving these devices. Our research revealed that about 45% of all patients receiving the devices in the Medicare age group were age 75 or older." In addition, the results showed that 15% of recipients were age 85 or older.

"ICDs may have been implanted when there was little empirical evidence to support their use. Because subjects over age 75 were specifically excluded from the randomized clinical trials [of ICDs,] there is no scientific evidence to support the notion that ICDs are safe or effective in this group," Dr. Kato said. "We really need to conduct randomized clinical trials in the excluded groups to determine safety and efficacy. If there is a lot of off-label use for a specific indication, then it stands to reason that clinical trials should be conducted to determine the safety and efficacy of the device for these specific indications.

"Off-label use does not necessarily mean that the use was without benefit or was unsafe," he noted. "Off-label use is simply the use of the device for conditions that were not tested during the randomized clinical trials."

The Centers for Medicare and Medicaid Services, in a 2005 decision memo on ICD use, noted that only 10% of patients who were enrolled in the two largest ICD trials were aged 75 or older, and as a consequence "the implantation of a defibrillator in the most elderly patients should be carefully considered and not routinely recommended," the memo said (CAG-00157R3).

Dr. Kato’s study of Massachusetts ICD usage also showed disproportionate placement of ICDs in men. During 1998-2008, men received ICDs three- to eightfold more often than did women for primary prevention indications, and three- to ninefold more often for secondary prevention.

These findings raise issues of a sex bias or a disease bias that favored men over women for ICD placement, he said. "In general, men have a higher risk for and greater rates of heart attack and coronary artery disease than women, hence men should probably be more likely to receive an ICD. But this merits consideration since results from other studies have also identified the same frequency differences by gender," said Dr. Kato.

The analyses used data compiled by the Massachusetts Department of Health and Human Services on hospital case mix and charge, as well as population estimates from the National Center for Health Statistics.

During the 11-year period studied, the rate of off-label ICD use for primary prevention indications ranged from 28% to 50%, depending on the year. In 2008, about 45% of Massachusetts patients who received an ICD had at least one off-label clinical feature, with age being an off-label factor for about 28% of all recipients. Primary-prevention use, which totaled 13,801 patients over the 11 years studied, occurred in patients with a diagnosis of heart failure or cardiomyopathy.

In 2008, about 45% of patients who received an ICD for secondary prevention had an off-label feature. Secondary-prevention use, which occurred in a total of 1,923 patients in the 11 years studied, included the indications of a history of cardiac arrest or ventricular arrhythmia during the year prior to ICD placement in patients who did not have a primary-prevention indication.

Criteria that led to exclusion from the ICD efficacy trials and hence constitute markers of off-label use included patients undergoing simultaneous percutaneous coronary intervention or coronary artery bypass surgery, and patients with a recent acute MI, renal failure, liver failure, neurologic failure, solid tumor, or dementia, as well as patients on dialysis, and patients aged 75 or older or aged 19 or younger.

Dr. Kato and his associates on the study said that they had no disclosures.

NEW ORLEANS – Nearly half of patients who received an implantable cardioverter defibrillator in Massachusetts during 1998-2008 had at least one clinical factor that categorized them as an off-label recipient, based on the exclusion criteria used in the clinical trials that established the efficacy of these devices.

The most common off-label use occurred in patients aged either 75 or older or 19 or younger, which in both cases put them outside of the age enrollment criteria for the implantable cardioverter defibrillator (ICD) trials, Dr. Norman S. Kato reported while presenting a poster at the annual meeting of the American College of Cardiology.

ICDs given to patients outside the age range that was tested in trials accounted for well over a quarter of all ICD use in Massachusetts during the period studied, and more than half of all off-label use. Other common off-label ICD uses occurred in patients with renal insufficiency or a recent acute MI, reported Dr. Kato, a cardiothoracic surgeon in Encino, Calif., who has consulted with the Food and Drug Administration, and his associates in their poster (J. Am Coll. Cardiol. 2011;57:E184).

Their analysis, which included 15,724 ICD recipients during the 11-year period studied, represents "the first analysis [of ICD use] to encompass all patients who have received this technology in a single state," he said in an interview. But he also cautioned that "it would be incorrect to generalize these results to other states, or to assume anything about practice patterns in Massachusetts" in the years following 2008.

"The key finding from our study was that patients over age 65 represent a significant portion of the population receiving these devices. Our research revealed that about 45% of all patients receiving the devices in the Medicare age group were age 75 or older." In addition, the results showed that 15% of recipients were age 85 or older.

"ICDs may have been implanted when there was little empirical evidence to support their use. Because subjects over age 75 were specifically excluded from the randomized clinical trials [of ICDs,] there is no scientific evidence to support the notion that ICDs are safe or effective in this group," Dr. Kato said. "We really need to conduct randomized clinical trials in the excluded groups to determine safety and efficacy. If there is a lot of off-label use for a specific indication, then it stands to reason that clinical trials should be conducted to determine the safety and efficacy of the device for these specific indications.

"Off-label use does not necessarily mean that the use was without benefit or was unsafe," he noted. "Off-label use is simply the use of the device for conditions that were not tested during the randomized clinical trials."

The Centers for Medicare and Medicaid Services, in a 2005 decision memo on ICD use, noted that only 10% of patients who were enrolled in the two largest ICD trials were aged 75 or older, and as a consequence "the implantation of a defibrillator in the most elderly patients should be carefully considered and not routinely recommended," the memo said (CAG-00157R3).

Dr. Kato’s study of Massachusetts ICD usage also showed disproportionate placement of ICDs in men. During 1998-2008, men received ICDs three- to eightfold more often than did women for primary prevention indications, and three- to ninefold more often for secondary prevention.

These findings raise issues of a sex bias or a disease bias that favored men over women for ICD placement, he said. "In general, men have a higher risk for and greater rates of heart attack and coronary artery disease than women, hence men should probably be more likely to receive an ICD. But this merits consideration since results from other studies have also identified the same frequency differences by gender," said Dr. Kato.

The analyses used data compiled by the Massachusetts Department of Health and Human Services on hospital case mix and charge, as well as population estimates from the National Center for Health Statistics.

During the 11-year period studied, the rate of off-label ICD use for primary prevention indications ranged from 28% to 50%, depending on the year. In 2008, about 45% of Massachusetts patients who received an ICD had at least one off-label clinical feature, with age being an off-label factor for about 28% of all recipients. Primary-prevention use, which totaled 13,801 patients over the 11 years studied, occurred in patients with a diagnosis of heart failure or cardiomyopathy.

In 2008, about 45% of patients who received an ICD for secondary prevention had an off-label feature. Secondary-prevention use, which occurred in a total of 1,923 patients in the 11 years studied, included the indications of a history of cardiac arrest or ventricular arrhythmia during the year prior to ICD placement in patients who did not have a primary-prevention indication.

Criteria that led to exclusion from the ICD efficacy trials and hence constitute markers of off-label use included patients undergoing simultaneous percutaneous coronary intervention or coronary artery bypass surgery, and patients with a recent acute MI, renal failure, liver failure, neurologic failure, solid tumor, or dementia, as well as patients on dialysis, and patients aged 75 or older or aged 19 or younger.

Dr. Kato and his associates on the study said that they had no disclosures.