Sara Freeman

STOCKHOLM – Data from the Swedish National Diabetes Registry add to evidence that high blood glucose levels increase the risk for dementia in individuals with type 2 diabetes and imply that better glycemic control might potentially help prevent such cognitive decline.

In the large observational study, A1C levels in excess of 10% increased the rate of dementia by 23%-77% depending on the time-fixed or time-updated statistical analysis performed, with hazard ratios (HRs) of 1.23 and 1.77, respectively, compared with a reference A1C of less than 6%.

Sara Freeman/Frontline Medical News

“An A1C between 6% and 7% was associated with a lower [HR, 0.82; 95% confidence interval, 0.86-0.91; P <.001] risk of any dementia compared to the reference, but as A1C increased and was above 10% [HR, 1.23; 95% CI, 1.11-1.35; P <.001] the risk was higher for individuals,” Dr. Aidin Rawshani reported at the annual meeting of the European Association for the Study of Diabetes.

For the study, Dr. Rawshani and his colleagues at the Institute of Medicine at the University of Gothenburg (Sweden) identified all individuals with type 2 diabetes (T2DM) who were registered in the Swedish National Diabetes Registry between 2003 and 2012 and who did not have dementia at enrollment. Data on individuals’ socioeconomic status, hospital admissions, outpatient visits, and deaths were then obtained from four Swedish databases and ICD-10 codes to identify those who later developed Alzheimer’s or vascular, unspecified, or any dementia.

Over a mean follow-up of 4.8 years, accounting for 1.7 million person-years, there were 353,214 individuals with T2DM without dementia at enrollment into the registry. Of these, 13,159 were reported to have any dementia, with 3,499 and 3,377 having Alzheimer disease or vascular dementia.

Cox regression analysis was used to assess the association between dementia and glycemic control, as well as other pertinent patient characteristics, risk factors, complications and comorbidities, and medication use. All covariates were modeled as both time-dependent and time-variable predictors.

The study population was divided into six groups according to baseline A1C: <6% (n = 118,433); 6% to <7% (n = 117,397); 7% to <8% (n = 49,049); 8% to <9% (n = 23,143); 9% to <10% (n = 9,096); ≥10% (n = 8,354). Over half (55%-60%) of subjects were men, the mean age was approximately 68 years, and the duration of diabetes ranged from 4 to 10 years.

Dr. Rawshani reported that the crude event rate for any dementia was 7.25 cases per 1,000 person-years for the lowest (<6%) and 8.47 for the highest (≥10%) levels of HbA_1c. The crude event rates for the other HbA_1c categories were 7.91, 8.75, 9.13, and 8.71 per 1,000 person-years, respectively.

Modeling A1C as a continuous variable showed that there was no dementia risk at an A1C of 6.7% but that it increased substantially thereafter. Dementia risk also was found to increase with increasing age, diastolic blood pressure, high-density-lipoprotein cholesterol, and low-density-lipoprotein cholesterol, he said.

Looking at time-updated covariates, individuals who developed microalbuminuria (HR, 1.22; 95% CI, 1.15-1.29; P <.001) or macroalbuminuria (HR, 1.39; 95% CI, 1.29-1.50; P <.001) had a higher risk for dementia than those without albuminuria.

A higher risk for dementia also was seen in patients who did not perform any daily physical activity versus those who did, with a HR of 2.21 (95% CI, 2.05-2.38; P <.001).

Comorbid stroke increased the risk for dementia by 43% (HR, 1.43; 95% CI, 1.34-1.53; P <.001), with little risk increase for comorbid atrial fibrillation (HR, 1.11; 95% CI, 1.04-1.18; P <.003) or coronary heart disease (HR, 1.02; 95% CI, 1.02-1.16; P <.009).

Conversely, the use of statins (HR, 0.87; 95% CI, 0.82-0.92; P <.001) and antihypertensive medication (HR, 0.69; 95% CI, 0.64-0.73; P <.001) was associated with lower dementia risk.

The respective Cox analysis–predicted survival rates at 10 years for the patients who did and did not develop dementia during follow-up were 40% and 70%.

“Our conclusion is that higher A1C levels are associated with an increased risk of dementia among persons with type 2 diabetes,” Dr. Rawshani said.

“The conclusion is interesting,” Dr. Naveed Sattar, professor of metabolic medicine at the Institute of Cardiovascular and Medical Sciences, University of Glasgow (Scotland), said in an interview. Dr. Sattar, who was not involved in the study, said that, while interesting, there was no mention that the very lowest blood glucose levels also were linked to an increased risk. There was a J-shaped curve, he observed.

“In people who have very low blood glucose levels, below guideline levels, I suspect that there are other reasons that they are sick and their A1C is low because of this and that then leads to dementia.” Dr. Sattar observed. He added that perhaps it was not necessarily the hyperglycemia causing dementia, it was more likely a case of reverse causality.

“The study showed clearly that high BMI, high LDL, and high blood pressure were also associated with more dementia,” Dr. Sattar said. “And, it also showed that being on antihypertensives and cholesterol-lowering tablets gives you a low risk of dementia,” he added. “So the things we are doing in diabetes to keep blood pressure down, smoking down, cholesterol down, are working and, together with keeping hemoglobin in the normal range, should help to lower the risk of dementia. That’s epidemiology, and we now need the trials to prove it, but it’s going to be very, very tough.”

Dr. Rawshani did not report having any disclosures. Dr. Sattar said that he had no disclosures relevant to his comments.

STOCKHOLM – Data from the Swedish National Diabetes Registry add to evidence that high blood glucose levels increase the risk for dementia in individuals with type 2 diabetes and imply that better glycemic control might potentially help prevent such cognitive decline.

In the large observational study, A1C levels in excess of 10% increased the rate of dementia by 23%-77% depending on the time-fixed or time-updated statistical analysis performed, with hazard ratios (HRs) of 1.23 and 1.77, respectively, compared with a reference A1C of less than 6%.

Sara Freeman/Frontline Medical News

“An A1C between 6% and 7% was associated with a lower [HR, 0.82; 95% confidence interval, 0.86-0.91; P <.001] risk of any dementia compared to the reference, but as A1C increased and was above 10% [HR, 1.23; 95% CI, 1.11-1.35; P <.001] the risk was higher for individuals,” Dr. Aidin Rawshani reported at the annual meeting of the European Association for the Study of Diabetes.

For the study, Dr. Rawshani and his colleagues at the Institute of Medicine at the University of Gothenburg (Sweden) identified all individuals with type 2 diabetes (T2DM) who were registered in the Swedish National Diabetes Registry between 2003 and 2012 and who did not have dementia at enrollment. Data on individuals’ socioeconomic status, hospital admissions, outpatient visits, and deaths were then obtained from four Swedish databases and ICD-10 codes to identify those who later developed Alzheimer’s or vascular, unspecified, or any dementia.

Over a mean follow-up of 4.8 years, accounting for 1.7 million person-years, there were 353,214 individuals with T2DM without dementia at enrollment into the registry. Of these, 13,159 were reported to have any dementia, with 3,499 and 3,377 having Alzheimer disease or vascular dementia.

Cox regression analysis was used to assess the association between dementia and glycemic control, as well as other pertinent patient characteristics, risk factors, complications and comorbidities, and medication use. All covariates were modeled as both time-dependent and time-variable predictors.

The study population was divided into six groups according to baseline A1C: <6% (n = 118,433); 6% to <7% (n = 117,397); 7% to <8% (n = 49,049); 8% to <9% (n = 23,143); 9% to <10% (n = 9,096); ≥10% (n = 8,354). Over half (55%-60%) of subjects were men, the mean age was approximately 68 years, and the duration of diabetes ranged from 4 to 10 years.

Dr. Rawshani reported that the crude event rate for any dementia was 7.25 cases per 1,000 person-years for the lowest (<6%) and 8.47 for the highest (≥10%) levels of HbA_1c. The crude event rates for the other HbA_1c categories were 7.91, 8.75, 9.13, and 8.71 per 1,000 person-years, respectively.

Modeling A1C as a continuous variable showed that there was no dementia risk at an A1C of 6.7% but that it increased substantially thereafter. Dementia risk also was found to increase with increasing age, diastolic blood pressure, high-density-lipoprotein cholesterol, and low-density-lipoprotein cholesterol, he said.

Looking at time-updated covariates, individuals who developed microalbuminuria (HR, 1.22; 95% CI, 1.15-1.29; P <.001) or macroalbuminuria (HR, 1.39; 95% CI, 1.29-1.50; P <.001) had a higher risk for dementia than those without albuminuria.

A higher risk for dementia also was seen in patients who did not perform any daily physical activity versus those who did, with a HR of 2.21 (95% CI, 2.05-2.38; P <.001).

Comorbid stroke increased the risk for dementia by 43% (HR, 1.43; 95% CI, 1.34-1.53; P <.001), with little risk increase for comorbid atrial fibrillation (HR, 1.11; 95% CI, 1.04-1.18; P <.003) or coronary heart disease (HR, 1.02; 95% CI, 1.02-1.16; P <.009).

Conversely, the use of statins (HR, 0.87; 95% CI, 0.82-0.92; P <.001) and antihypertensive medication (HR, 0.69; 95% CI, 0.64-0.73; P <.001) was associated with lower dementia risk.

The respective Cox analysis–predicted survival rates at 10 years for the patients who did and did not develop dementia during follow-up were 40% and 70%.

“Our conclusion is that higher A1C levels are associated with an increased risk of dementia among persons with type 2 diabetes,” Dr. Rawshani said.

“The conclusion is interesting,” Dr. Naveed Sattar, professor of metabolic medicine at the Institute of Cardiovascular and Medical Sciences, University of Glasgow (Scotland), said in an interview. Dr. Sattar, who was not involved in the study, said that, while interesting, there was no mention that the very lowest blood glucose levels also were linked to an increased risk. There was a J-shaped curve, he observed.

“In people who have very low blood glucose levels, below guideline levels, I suspect that there are other reasons that they are sick and their A1C is low because of this and that then leads to dementia.” Dr. Sattar observed. He added that perhaps it was not necessarily the hyperglycemia causing dementia, it was more likely a case of reverse causality.

“The study showed clearly that high BMI, high LDL, and high blood pressure were also associated with more dementia,” Dr. Sattar said. “And, it also showed that being on antihypertensives and cholesterol-lowering tablets gives you a low risk of dementia,” he added. “So the things we are doing in diabetes to keep blood pressure down, smoking down, cholesterol down, are working and, together with keeping hemoglobin in the normal range, should help to lower the risk of dementia. That’s epidemiology, and we now need the trials to prove it, but it’s going to be very, very tough.”

Dr. Rawshani did not report having any disclosures. Dr. Sattar said that he had no disclosures relevant to his comments.

STOCKHOLM – Data from the Swedish National Diabetes Registry add to evidence that high blood glucose levels increase the risk for dementia in individuals with type 2 diabetes and imply that better glycemic control might potentially help prevent such cognitive decline.

In the large observational study, A1C levels in excess of 10% increased the rate of dementia by 23%-77% depending on the time-fixed or time-updated statistical analysis performed, with hazard ratios (HRs) of 1.23 and 1.77, respectively, compared with a reference A1C of less than 6%.

Sara Freeman/Frontline Medical News

“An A1C between 6% and 7% was associated with a lower [HR, 0.82; 95% confidence interval, 0.86-0.91; P <.001] risk of any dementia compared to the reference, but as A1C increased and was above 10% [HR, 1.23; 95% CI, 1.11-1.35; P <.001] the risk was higher for individuals,” Dr. Aidin Rawshani reported at the annual meeting of the European Association for the Study of Diabetes.

For the study, Dr. Rawshani and his colleagues at the Institute of Medicine at the University of Gothenburg (Sweden) identified all individuals with type 2 diabetes (T2DM) who were registered in the Swedish National Diabetes Registry between 2003 and 2012 and who did not have dementia at enrollment. Data on individuals’ socioeconomic status, hospital admissions, outpatient visits, and deaths were then obtained from four Swedish databases and ICD-10 codes to identify those who later developed Alzheimer’s or vascular, unspecified, or any dementia.

Over a mean follow-up of 4.8 years, accounting for 1.7 million person-years, there were 353,214 individuals with T2DM without dementia at enrollment into the registry. Of these, 13,159 were reported to have any dementia, with 3,499 and 3,377 having Alzheimer disease or vascular dementia.

Cox regression analysis was used to assess the association between dementia and glycemic control, as well as other pertinent patient characteristics, risk factors, complications and comorbidities, and medication use. All covariates were modeled as both time-dependent and time-variable predictors.

The study population was divided into six groups according to baseline A1C: <6% (n = 118,433); 6% to <7% (n = 117,397); 7% to <8% (n = 49,049); 8% to <9% (n = 23,143); 9% to <10% (n = 9,096); ≥10% (n = 8,354). Over half (55%-60%) of subjects were men, the mean age was approximately 68 years, and the duration of diabetes ranged from 4 to 10 years.

Dr. Rawshani reported that the crude event rate for any dementia was 7.25 cases per 1,000 person-years for the lowest (<6%) and 8.47 for the highest (≥10%) levels of HbA_1c. The crude event rates for the other HbA_1c categories were 7.91, 8.75, 9.13, and 8.71 per 1,000 person-years, respectively.

Modeling A1C as a continuous variable showed that there was no dementia risk at an A1C of 6.7% but that it increased substantially thereafter. Dementia risk also was found to increase with increasing age, diastolic blood pressure, high-density-lipoprotein cholesterol, and low-density-lipoprotein cholesterol, he said.

Looking at time-updated covariates, individuals who developed microalbuminuria (HR, 1.22; 95% CI, 1.15-1.29; P <.001) or macroalbuminuria (HR, 1.39; 95% CI, 1.29-1.50; P <.001) had a higher risk for dementia than those without albuminuria.

A higher risk for dementia also was seen in patients who did not perform any daily physical activity versus those who did, with a HR of 2.21 (95% CI, 2.05-2.38; P <.001).

Comorbid stroke increased the risk for dementia by 43% (HR, 1.43; 95% CI, 1.34-1.53; P <.001), with little risk increase for comorbid atrial fibrillation (HR, 1.11; 95% CI, 1.04-1.18; P <.003) or coronary heart disease (HR, 1.02; 95% CI, 1.02-1.16; P <.009).

Conversely, the use of statins (HR, 0.87; 95% CI, 0.82-0.92; P <.001) and antihypertensive medication (HR, 0.69; 95% CI, 0.64-0.73; P <.001) was associated with lower dementia risk.

The respective Cox analysis–predicted survival rates at 10 years for the patients who did and did not develop dementia during follow-up were 40% and 70%.

“Our conclusion is that higher A1C levels are associated with an increased risk of dementia among persons with type 2 diabetes,” Dr. Rawshani said.

“The conclusion is interesting,” Dr. Naveed Sattar, professor of metabolic medicine at the Institute of Cardiovascular and Medical Sciences, University of Glasgow (Scotland), said in an interview. Dr. Sattar, who was not involved in the study, said that, while interesting, there was no mention that the very lowest blood glucose levels also were linked to an increased risk. There was a J-shaped curve, he observed.

“In people who have very low blood glucose levels, below guideline levels, I suspect that there are other reasons that they are sick and their A1C is low because of this and that then leads to dementia.” Dr. Sattar observed. He added that perhaps it was not necessarily the hyperglycemia causing dementia, it was more likely a case of reverse causality.

“The study showed clearly that high BMI, high LDL, and high blood pressure were also associated with more dementia,” Dr. Sattar said. “And, it also showed that being on antihypertensives and cholesterol-lowering tablets gives you a low risk of dementia,” he added. “So the things we are doing in diabetes to keep blood pressure down, smoking down, cholesterol down, are working and, together with keeping hemoglobin in the normal range, should help to lower the risk of dementia. That’s epidemiology, and we now need the trials to prove it, but it’s going to be very, very tough.”

Dr. Rawshani did not report having any disclosures. Dr. Sattar said that he had no disclosures relevant to his comments.

STOCKHOLM – Data from the Swedish National Diabetes Registry add to evidence that high blood glucose levels increase the risk for dementia in individuals with type 2 diabetes and imply that better glycemic control might potentially help prevent such cognitive decline.

In the large observational study, hemoglobin A_1c levels in excess of 10% increased the rate of dementia by 23%-77% depending on the time-fixed or time-updated statistical analysis performed, with hazard ratios (HRs) of 1.23 and 1.77, respectively, compared with a reference HbA_1c of less than 6%.

Sara Freeman/Frontline Medical News

“An HbA_1c between 6% and 7% was associated with a lower [HR, 0.82; 95% confidence interval, 0.86-0.91; P <.001] risk of any dementia compared to the reference, but as HbA_1c increased and was above 10% [HR, 1.23; 95% CI, 1.11-1.35; P <.001] the risk was higher for individuals,” Dr. Aidin Rawshani reported at the annual meeting of the European Association for the Study of Diabetes.

For the study, Dr. Rawshani and his colleagues at the Institute of Medicine at the University of Gothenburg (Sweden) identified all individuals with type 2 diabetes (2DM) who were registered in the Swedish National Diabetes Registry between 2003 and 2012 and who did not have dementia at enrollment. Data on individuals’ socioeconomic status, hospital admissions, outpatient visits, and deaths were then obtained from four Swedish databases and ICD-10 codes to identify those who later developed Alzheimer’s or vascular, unspecified, or any dementia.

Over a mean follow-up of 4.8 years, accounting for 1.7 million person-years, there were 353,214 individuals with 2DM without dementia at enrollment into the registry. Of these, 13,159 were reported to have any dementia, with 3,499 and 3,377 having Alzheimer’s disease or vascular dementia.

Cox regression analysis was used to assess the association between dementia and glycemic control, as well as other pertinent patient characteristics, risk factors, complications and comorbidities, and medication use. All covariates were modeled as both time-dependent and time-variable predictors.

The study population was divided into six groups according to baseline HbA_1c: <6% (n = 118,433); 6% to <7% (n = 117,397); 7% to <8% (n = 49,049); 8% to <9% (n = 23,143); 9% to <10% (n = 9,096); ≥10% (n = 8,354). Over half (55%-60%) of subjects were men, the mean age was approximately 68 years, and the duration of diabetes ranged from 4 to 10 years.

Dr. Rawshani reported that the crude event rate for any dementia was 7.25 cases per 1,000 person-years for the lowest (<6%) and 8.47 for the highest (≥10%) levels of HbA_1c. The crude event rates for the other HbA_1c categories were 7.91, 8.75, 9.13, and 8.71 per 1,000 person-years, respectively.

Modeling HbA_1c as a continuous variable showed that there was no dementia risk at an HbA_1c of 6.7% but that it increased substantially thereafter. Dementia risk also was found to increase with increasing age, diastolic blood pressure, high-density-lipoprotein cholesterol, and low-density-lipoprotein cholesterol, he said.

Looking at time-updated covariates, individuals who developed microalbuminuria (HR, 1.22; 95% CI, 1.15-1.29; P <.001) or macroalbuminuria (HR, 1.39; 95% CI, 1.29-1.50; P <.001) had a higher risk for dementia than those without albuminuria.

A higher risk for dementia also was seen in patients who did not perform any daily physical activity versus those who did, with a HR of 2.21 (95% CI, 2.05-2.38; P <.001).

Comorbid stroke increased the risk for dementia by 43% (HR, 1.43; 95% CI, 1.34-1.53; P <.001), with little risk increase for comorbid atrial fibrillation (HR, 1.11; 95% CI, 1.04-1.18; P <.003) or coronary heart disease (HR, 1.02; 95% CI, 1.02-1.16; P <.009).

Conversely, the use of statins (HR, 0.87; 95% CI, 0.82-0.92; P <.001) and antihypertensive medication (HR, 0.69; 95% CI, 0.64-0.73; P <.001) was associated with lower dementia risk.

The respective Cox analysis–predicted survival rates at 10 years for the patients who did and did not develop dementia during follow-up were 40% and 70%.

“Our conclusion is that higher HbA_1c levels are associated with an increased risk of dementia among persons with type 2 diabetes,” Dr. Rawshani said.

“The conclusion is interesting,” Dr. Naveed Sattar, professor of metabolic medicine at the Institute of Cardiovascular and Medical Sciences, University of Glasgow (Scotland), said in an interview. Dr. Sattar, who was not involved in the study, said that, while interesting, there was no mention that the very lowest blood glucose levels also were linked to an increased risk. There was a J-shaped curve, he observed.

“In people who have very low blood glucose levels, below guideline levels, I suspect that there are other reasons that they are sick and they’re hemoglobin A_1c is low because of this and that then leads to dementia.” Dr. Sattar observed. He added that perhaps it was not necessarily the hyperglycemia causing dementia, it was more likely a case of reverse causality.

“The study showed clearly that high BMI, high LDL, and high blood pressure were also associated with more dementia,” Dr. Sattar said. “And, it also showed that being on antihypertensives and cholesterol-lowering tablets gives you a low risk of dementia,” he added. “So the things we are doing in diabetes to keep blood pressure down, smoking down, cholesterol down, are working and, together with keeping hemoglobin in the normal range, should help to lower the risk of dementia. That’s epidemiology, and we now need the trials to prove it, but it’s going to be very, very tough.”

Dr. Rawshani did not report having any disclosures. Dr. Sattar said that he had no disclosures relevant to his comments.

STOCKHOLM – Data from the Swedish National Diabetes Registry add to evidence that high blood glucose levels increase the risk for dementia in individuals with type 2 diabetes and imply that better glycemic control might potentially help prevent such cognitive decline.

In the large observational study, hemoglobin A_1c levels in excess of 10% increased the rate of dementia by 23%-77% depending on the time-fixed or time-updated statistical analysis performed, with hazard ratios (HRs) of 1.23 and 1.77, respectively, compared with a reference HbA_1c of less than 6%.

Sara Freeman/Frontline Medical News

“An HbA_1c between 6% and 7% was associated with a lower [HR, 0.82; 95% confidence interval, 0.86-0.91; P <.001] risk of any dementia compared to the reference, but as HbA_1c increased and was above 10% [HR, 1.23; 95% CI, 1.11-1.35; P <.001] the risk was higher for individuals,” Dr. Aidin Rawshani reported at the annual meeting of the European Association for the Study of Diabetes.

For the study, Dr. Rawshani and his colleagues at the Institute of Medicine at the University of Gothenburg (Sweden) identified all individuals with type 2 diabetes (2DM) who were registered in the Swedish National Diabetes Registry between 2003 and 2012 and who did not have dementia at enrollment. Data on individuals’ socioeconomic status, hospital admissions, outpatient visits, and deaths were then obtained from four Swedish databases and ICD-10 codes to identify those who later developed Alzheimer’s or vascular, unspecified, or any dementia.

Over a mean follow-up of 4.8 years, accounting for 1.7 million person-years, there were 353,214 individuals with 2DM without dementia at enrollment into the registry. Of these, 13,159 were reported to have any dementia, with 3,499 and 3,377 having Alzheimer’s disease or vascular dementia.

Cox regression analysis was used to assess the association between dementia and glycemic control, as well as other pertinent patient characteristics, risk factors, complications and comorbidities, and medication use. All covariates were modeled as both time-dependent and time-variable predictors.

The study population was divided into six groups according to baseline HbA_1c: <6% (n = 118,433); 6% to <7% (n = 117,397); 7% to <8% (n = 49,049); 8% to <9% (n = 23,143); 9% to <10% (n = 9,096); ≥10% (n = 8,354). Over half (55%-60%) of subjects were men, the mean age was approximately 68 years, and the duration of diabetes ranged from 4 to 10 years.

Dr. Rawshani reported that the crude event rate for any dementia was 7.25 cases per 1,000 person-years for the lowest (<6%) and 8.47 for the highest (≥10%) levels of HbA_1c. The crude event rates for the other HbA_1c categories were 7.91, 8.75, 9.13, and 8.71 per 1,000 person-years, respectively.

Modeling HbA_1c as a continuous variable showed that there was no dementia risk at an HbA_1c of 6.7% but that it increased substantially thereafter. Dementia risk also was found to increase with increasing age, diastolic blood pressure, high-density-lipoprotein cholesterol, and low-density-lipoprotein cholesterol, he said.

Looking at time-updated covariates, individuals who developed microalbuminuria (HR, 1.22; 95% CI, 1.15-1.29; P <.001) or macroalbuminuria (HR, 1.39; 95% CI, 1.29-1.50; P <.001) had a higher risk for dementia than those without albuminuria.

A higher risk for dementia also was seen in patients who did not perform any daily physical activity versus those who did, with a HR of 2.21 (95% CI, 2.05-2.38; P <.001).

Comorbid stroke increased the risk for dementia by 43% (HR, 1.43; 95% CI, 1.34-1.53; P <.001), with little risk increase for comorbid atrial fibrillation (HR, 1.11; 95% CI, 1.04-1.18; P <.003) or coronary heart disease (HR, 1.02; 95% CI, 1.02-1.16; P <.009).

Conversely, the use of statins (HR, 0.87; 95% CI, 0.82-0.92; P <.001) and antihypertensive medication (HR, 0.69; 95% CI, 0.64-0.73; P <.001) was associated with lower dementia risk.

The respective Cox analysis–predicted survival rates at 10 years for the patients who did and did not develop dementia during follow-up were 40% and 70%.

“Our conclusion is that higher HbA_1c levels are associated with an increased risk of dementia among persons with type 2 diabetes,” Dr. Rawshani said.

“The conclusion is interesting,” Dr. Naveed Sattar, professor of metabolic medicine at the Institute of Cardiovascular and Medical Sciences, University of Glasgow (Scotland), said in an interview. Dr. Sattar, who was not involved in the study, said that, while interesting, there was no mention that the very lowest blood glucose levels also were linked to an increased risk. There was a J-shaped curve, he observed.

“In people who have very low blood glucose levels, below guideline levels, I suspect that there are other reasons that they are sick and they’re hemoglobin A_1c is low because of this and that then leads to dementia.” Dr. Sattar observed. He added that perhaps it was not necessarily the hyperglycemia causing dementia, it was more likely a case of reverse causality.

“The study showed clearly that high BMI, high LDL, and high blood pressure were also associated with more dementia,” Dr. Sattar said. “And, it also showed that being on antihypertensives and cholesterol-lowering tablets gives you a low risk of dementia,” he added. “So the things we are doing in diabetes to keep blood pressure down, smoking down, cholesterol down, are working and, together with keeping hemoglobin in the normal range, should help to lower the risk of dementia. That’s epidemiology, and we now need the trials to prove it, but it’s going to be very, very tough.”

Dr. Rawshani did not report having any disclosures. Dr. Sattar said that he had no disclosures relevant to his comments.

STOCKHOLM – Data from the Swedish National Diabetes Registry add to evidence that high blood glucose levels increase the risk for dementia in individuals with type 2 diabetes and imply that better glycemic control might potentially help prevent such cognitive decline.

In the large observational study, hemoglobin A_1c levels in excess of 10% increased the rate of dementia by 23%-77% depending on the time-fixed or time-updated statistical analysis performed, with hazard ratios (HRs) of 1.23 and 1.77, respectively, compared with a reference HbA_1c of less than 6%.

Sara Freeman/Frontline Medical News

“An HbA_1c between 6% and 7% was associated with a lower [HR, 0.82; 95% confidence interval, 0.86-0.91; P <.001] risk of any dementia compared to the reference, but as HbA_1c increased and was above 10% [HR, 1.23; 95% CI, 1.11-1.35; P <.001] the risk was higher for individuals,” Dr. Aidin Rawshani reported at the annual meeting of the European Association for the Study of Diabetes.

For the study, Dr. Rawshani and his colleagues at the Institute of Medicine at the University of Gothenburg (Sweden) identified all individuals with type 2 diabetes (2DM) who were registered in the Swedish National Diabetes Registry between 2003 and 2012 and who did not have dementia at enrollment. Data on individuals’ socioeconomic status, hospital admissions, outpatient visits, and deaths were then obtained from four Swedish databases and ICD-10 codes to identify those who later developed Alzheimer’s or vascular, unspecified, or any dementia.

Over a mean follow-up of 4.8 years, accounting for 1.7 million person-years, there were 353,214 individuals with 2DM without dementia at enrollment into the registry. Of these, 13,159 were reported to have any dementia, with 3,499 and 3,377 having Alzheimer’s disease or vascular dementia.

Cox regression analysis was used to assess the association between dementia and glycemic control, as well as other pertinent patient characteristics, risk factors, complications and comorbidities, and medication use. All covariates were modeled as both time-dependent and time-variable predictors.

The study population was divided into six groups according to baseline HbA_1c: <6% (n = 118,433); 6% to <7% (n = 117,397); 7% to <8% (n = 49,049); 8% to <9% (n = 23,143); 9% to <10% (n = 9,096); ≥10% (n = 8,354). Over half (55%-60%) of subjects were men, the mean age was approximately 68 years, and the duration of diabetes ranged from 4 to 10 years.

Dr. Rawshani reported that the crude event rate for any dementia was 7.25 cases per 1,000 person-years for the lowest (<6%) and 8.47 for the highest (≥10%) levels of HbA_1c. The crude event rates for the other HbA_1c categories were 7.91, 8.75, 9.13, and 8.71 per 1,000 person-years, respectively.

Modeling HbA_1c as a continuous variable showed that there was no dementia risk at an HbA_1c of 6.7% but that it increased substantially thereafter. Dementia risk also was found to increase with increasing age, diastolic blood pressure, high-density-lipoprotein cholesterol, and low-density-lipoprotein cholesterol, he said.

Looking at time-updated covariates, individuals who developed microalbuminuria (HR, 1.22; 95% CI, 1.15-1.29; P <.001) or macroalbuminuria (HR, 1.39; 95% CI, 1.29-1.50; P <.001) had a higher risk for dementia than those without albuminuria.

A higher risk for dementia also was seen in patients who did not perform any daily physical activity versus those who did, with a HR of 2.21 (95% CI, 2.05-2.38; P <.001).

Comorbid stroke increased the risk for dementia by 43% (HR, 1.43; 95% CI, 1.34-1.53; P <.001), with little risk increase for comorbid atrial fibrillation (HR, 1.11; 95% CI, 1.04-1.18; P <.003) or coronary heart disease (HR, 1.02; 95% CI, 1.02-1.16; P <.009).

Conversely, the use of statins (HR, 0.87; 95% CI, 0.82-0.92; P <.001) and antihypertensive medication (HR, 0.69; 95% CI, 0.64-0.73; P <.001) was associated with lower dementia risk.

The respective Cox analysis–predicted survival rates at 10 years for the patients who did and did not develop dementia during follow-up were 40% and 70%.

“Our conclusion is that higher HbA_1c levels are associated with an increased risk of dementia among persons with type 2 diabetes,” Dr. Rawshani said.

“The conclusion is interesting,” Dr. Naveed Sattar, professor of metabolic medicine at the Institute of Cardiovascular and Medical Sciences, University of Glasgow (Scotland), said in an interview. Dr. Sattar, who was not involved in the study, said that, while interesting, there was no mention that the very lowest blood glucose levels also were linked to an increased risk. There was a J-shaped curve, he observed.

“In people who have very low blood glucose levels, below guideline levels, I suspect that there are other reasons that they are sick and they’re hemoglobin A_1c is low because of this and that then leads to dementia.” Dr. Sattar observed. He added that perhaps it was not necessarily the hyperglycemia causing dementia, it was more likely a case of reverse causality.

“The study showed clearly that high BMI, high LDL, and high blood pressure were also associated with more dementia,” Dr. Sattar said. “And, it also showed that being on antihypertensives and cholesterol-lowering tablets gives you a low risk of dementia,” he added. “So the things we are doing in diabetes to keep blood pressure down, smoking down, cholesterol down, are working and, together with keeping hemoglobin in the normal range, should help to lower the risk of dementia. That’s epidemiology, and we now need the trials to prove it, but it’s going to be very, very tough.”

Dr. Rawshani did not report having any disclosures. Dr. Sattar said that he had no disclosures relevant to his comments.

LONDON – Further data from two large-scale diabetes trials continue to indicate that there is no increased risk for heart failure with either lixisenatide or sitagliptin compared to placebo.

The findings from ELIXA (the evaluation of lixisenatide in acute coronary syndromes) and TECOS (the Trial Evaluating Cardiovascular Outcomes With Sitagliptin), presented at the annual congress of the European Society of Cardiology, provide reassuring evidence of the cardiovascular safety of both drugs, and add to the trials’ results previously presented at the 2015 annual scientific sessions of the American Diabetes Association, according to the key investigators for the separately-run trials.

Sara Freeman/Frontline Medical News

“ELIXA demonstrates the cardiovascular safety of lixisenatide,” Dr. Eldrin Lewis, associate professor of medicine at Harvard Medical School and of Brigham and Women’s Hospital in Boston. “Additional analyses indicate safety with respect to heart failure events as well as all-cause mortality, and the hazard ratio after heart failure hospitalizations demonstrate that this endpoint is very meaningful in diabetes as it is in other populations” he added. Furthermore, the neutral effects of lixisenatide were seen across a wide spectrum of heart failure risk.

TECOS investigator Dr. Paul Armstrong of the University of Alberta in Canada noted similar safety findings with sitagliptin. “We found no increase in the risk of heart failure or related adverse outcomes after sitagliptin therapy,” he said at a press briefing. “We can safely conclude that sitagliptin can be used in patients with type 2 diabetes without concern for worsening heart failure.”

ELIXA and TECOS were two phase 3, randomized, double blind placebo-controlled trials specifically designed to look at cardiovascular outcomes after treatment with the glucagon-like peptide 1 (GLP-1) receptor agonist lixisenatide (intended trade name Lyxumia) or the dipeptyl peptidase 4 (DPP-4) inhibitor sitagliptin (Januvia). The trials enrolled 6,068 and 14,671 patients, respectively, and were performed in the wake of prior trials that had suggested an increased risk for hospitalization for heart failure in patients treated with other DPP-4 inhibitors including saxagliptin (Onglyza) in the SAVOR-TIMI 53 trial and alogliptin (Nesina) in the EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial.

Although powered to show superiority of lixisenatide versus placebo in terms of cardiovascular safety, ELIXA was only able to establish noninferiority (HR, 1.02), but results were below limits for noninferiority set by the United States Food and Drug Administration, Dr. Lewis observed. In the updated analysis of ELIXA there was no difference between treatment with the lixisenatide and placebo for the primary composite cardiovascular endpoint plus heart failure hospitalization (hazard ratio, 0.97, 95% confidence interval 0.85-1.10) after 3 years of follow-up. There were also no differences in the rates of heart failure hospitalization (HR, 0.96, 95% CI 0.75-1.23), the primary endpoint plus heart failure hospitalization and coronary revascularization (HR=1.00, 95% CI 0.90-1.11), or death from any cause (HR, 0.94, 95% CI 0.78-1.13).Although the risk for heart failure hospitalization was found to be nine times higher in patients who had a prior history of heart failure in ELIXA than in those who did not there was there was no difference between treatment with the GLP-1 agonist or placebo in patients with (9.7% vs. 10.2%, HR, 0.93, 95% CI 0.66-1.30) or without (2.4% vs. 2.5%, HR, 0.97, 95% CI 0.67-1.40) a history of the disease.

The primary findings of TECOS have been published (doi:10.1056/NEJMoa1501352) and showed sitagliptin to be noninferior to placebo for the primary composite cardiovascular endpoint (HR,0.98; 95% CI, 0.88-1.09; P less than .001). Heart failure hospitalization rates were similar (HR, 1.00; 95% CI, 0.83-1.20; P = .98).

In the updated analysis of TECOS, the prespecified secondary endpoint of time to first hospitalization for heart failure did not differ between the placebo and sitagliptin arms (HR, 1.0; 95% CI, 0.84-1.20, P = .95), nor were there any differences between the treatments in terms of other prespecified secondary endpoints of hospitalization for heart failure or cardiovascular death (HR, 1.02, 95% CI 0.90-1.14, P =.74), or hospitalization for heart failure or all-cause death (HR, 1.00, 95% CI 0.90-1.11, P = .93).

Dr. Armstrong acknowledged that the findings of TECOS were in contrast to the SAVOR-TIMI 53 and EXAMINE trials but that this could be due to several factors: differences in the patients enrolled, the background care provided, and variation in the acquisition or definition of heart failure events between the trials. It could also be due to intrinsic differences among the DPP-4 inhibitors themselves or “chance.”

Dr. Gabriel Steg of Hôpital Bichat in Paris, France who provided independent comment after the presentation of the ELIXA data questioned the value of continuing to perform large-scale noninferiority studies assessing the cardiovascular safety of novel diabetes medicines. More than 150,000 patients have been studied in such trials to date which have shown noninferiority for cardiovascular outcomes.

“Non-inferiority trials are often mistakenly being interpreted as ‘lack of efficacy’ trials and can among nonspecialists generate skepticism regarding treatment of diabetes or the need to control glycemia,” he said. “My conclusion would be to suggest that it is time to stop wasting resources on noninferiority trials and to work on truly improving diabetes care.”

ELXIA was sponsored by Sanofi. Dr. Lewis disclosed receiving research funding from Sanofi, and other drug companies. TECOS was sponsored by Merck. Dr. Armstrong disclosed receiving research funding, educational grants and consulting fees from Merck as well as other companies. Dr. Steg had received research grants from and has acted as a consultant for Sanofi, Merck, and other companies.

LONDON – Further data from two large-scale diabetes trials continue to indicate that there is no increased risk for heart failure with either lixisenatide or sitagliptin compared to placebo.

The findings from ELIXA (the evaluation of lixisenatide in acute coronary syndromes) and TECOS (the Trial Evaluating Cardiovascular Outcomes With Sitagliptin), presented at the annual congress of the European Society of Cardiology, provide reassuring evidence of the cardiovascular safety of both drugs, and add to the trials’ results previously presented at the 2015 annual scientific sessions of the American Diabetes Association, according to the key investigators for the separately-run trials.

Sara Freeman/Frontline Medical News

“ELIXA demonstrates the cardiovascular safety of lixisenatide,” Dr. Eldrin Lewis, associate professor of medicine at Harvard Medical School and of Brigham and Women’s Hospital in Boston. “Additional analyses indicate safety with respect to heart failure events as well as all-cause mortality, and the hazard ratio after heart failure hospitalizations demonstrate that this endpoint is very meaningful in diabetes as it is in other populations” he added. Furthermore, the neutral effects of lixisenatide were seen across a wide spectrum of heart failure risk.

TECOS investigator Dr. Paul Armstrong of the University of Alberta in Canada noted similar safety findings with sitagliptin. “We found no increase in the risk of heart failure or related adverse outcomes after sitagliptin therapy,” he said at a press briefing. “We can safely conclude that sitagliptin can be used in patients with type 2 diabetes without concern for worsening heart failure.”

ELIXA and TECOS were two phase 3, randomized, double blind placebo-controlled trials specifically designed to look at cardiovascular outcomes after treatment with the glucagon-like peptide 1 (GLP-1) receptor agonist lixisenatide (intended trade name Lyxumia) or the dipeptyl peptidase 4 (DPP-4) inhibitor sitagliptin (Januvia). The trials enrolled 6,068 and 14,671 patients, respectively, and were performed in the wake of prior trials that had suggested an increased risk for hospitalization for heart failure in patients treated with other DPP-4 inhibitors including saxagliptin (Onglyza) in the SAVOR-TIMI 53 trial and alogliptin (Nesina) in the EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial.

Although powered to show superiority of lixisenatide versus placebo in terms of cardiovascular safety, ELIXA was only able to establish noninferiority (HR, 1.02), but results were below limits for noninferiority set by the United States Food and Drug Administration, Dr. Lewis observed. In the updated analysis of ELIXA there was no difference between treatment with the lixisenatide and placebo for the primary composite cardiovascular endpoint plus heart failure hospitalization (hazard ratio, 0.97, 95% confidence interval 0.85-1.10) after 3 years of follow-up. There were also no differences in the rates of heart failure hospitalization (HR, 0.96, 95% CI 0.75-1.23), the primary endpoint plus heart failure hospitalization and coronary revascularization (HR=1.00, 95% CI 0.90-1.11), or death from any cause (HR, 0.94, 95% CI 0.78-1.13).Although the risk for heart failure hospitalization was found to be nine times higher in patients who had a prior history of heart failure in ELIXA than in those who did not there was there was no difference between treatment with the GLP-1 agonist or placebo in patients with (9.7% vs. 10.2%, HR, 0.93, 95% CI 0.66-1.30) or without (2.4% vs. 2.5%, HR, 0.97, 95% CI 0.67-1.40) a history of the disease.

The primary findings of TECOS have been published (doi:10.1056/NEJMoa1501352) and showed sitagliptin to be noninferior to placebo for the primary composite cardiovascular endpoint (HR,0.98; 95% CI, 0.88-1.09; P less than .001). Heart failure hospitalization rates were similar (HR, 1.00; 95% CI, 0.83-1.20; P = .98).

In the updated analysis of TECOS, the prespecified secondary endpoint of time to first hospitalization for heart failure did not differ between the placebo and sitagliptin arms (HR, 1.0; 95% CI, 0.84-1.20, P = .95), nor were there any differences between the treatments in terms of other prespecified secondary endpoints of hospitalization for heart failure or cardiovascular death (HR, 1.02, 95% CI 0.90-1.14, P =.74), or hospitalization for heart failure or all-cause death (HR, 1.00, 95% CI 0.90-1.11, P = .93).

Dr. Armstrong acknowledged that the findings of TECOS were in contrast to the SAVOR-TIMI 53 and EXAMINE trials but that this could be due to several factors: differences in the patients enrolled, the background care provided, and variation in the acquisition or definition of heart failure events between the trials. It could also be due to intrinsic differences among the DPP-4 inhibitors themselves or “chance.”

Dr. Gabriel Steg of Hôpital Bichat in Paris, France who provided independent comment after the presentation of the ELIXA data questioned the value of continuing to perform large-scale noninferiority studies assessing the cardiovascular safety of novel diabetes medicines. More than 150,000 patients have been studied in such trials to date which have shown noninferiority for cardiovascular outcomes.

“Non-inferiority trials are often mistakenly being interpreted as ‘lack of efficacy’ trials and can among nonspecialists generate skepticism regarding treatment of diabetes or the need to control glycemia,” he said. “My conclusion would be to suggest that it is time to stop wasting resources on noninferiority trials and to work on truly improving diabetes care.”

ELXIA was sponsored by Sanofi. Dr. Lewis disclosed receiving research funding from Sanofi, and other drug companies. TECOS was sponsored by Merck. Dr. Armstrong disclosed receiving research funding, educational grants and consulting fees from Merck as well as other companies. Dr. Steg had received research grants from and has acted as a consultant for Sanofi, Merck, and other companies.

LONDON – Further data from two large-scale diabetes trials continue to indicate that there is no increased risk for heart failure with either lixisenatide or sitagliptin compared to placebo.

The findings from ELIXA (the evaluation of lixisenatide in acute coronary syndromes) and TECOS (the Trial Evaluating Cardiovascular Outcomes With Sitagliptin), presented at the annual congress of the European Society of Cardiology, provide reassuring evidence of the cardiovascular safety of both drugs, and add to the trials’ results previously presented at the 2015 annual scientific sessions of the American Diabetes Association, according to the key investigators for the separately-run trials.

Sara Freeman/Frontline Medical News

“ELIXA demonstrates the cardiovascular safety of lixisenatide,” Dr. Eldrin Lewis, associate professor of medicine at Harvard Medical School and of Brigham and Women’s Hospital in Boston. “Additional analyses indicate safety with respect to heart failure events as well as all-cause mortality, and the hazard ratio after heart failure hospitalizations demonstrate that this endpoint is very meaningful in diabetes as it is in other populations” he added. Furthermore, the neutral effects of lixisenatide were seen across a wide spectrum of heart failure risk.

TECOS investigator Dr. Paul Armstrong of the University of Alberta in Canada noted similar safety findings with sitagliptin. “We found no increase in the risk of heart failure or related adverse outcomes after sitagliptin therapy,” he said at a press briefing. “We can safely conclude that sitagliptin can be used in patients with type 2 diabetes without concern for worsening heart failure.”

ELIXA and TECOS were two phase 3, randomized, double blind placebo-controlled trials specifically designed to look at cardiovascular outcomes after treatment with the glucagon-like peptide 1 (GLP-1) receptor agonist lixisenatide (intended trade name Lyxumia) or the dipeptyl peptidase 4 (DPP-4) inhibitor sitagliptin (Januvia). The trials enrolled 6,068 and 14,671 patients, respectively, and were performed in the wake of prior trials that had suggested an increased risk for hospitalization for heart failure in patients treated with other DPP-4 inhibitors including saxagliptin (Onglyza) in the SAVOR-TIMI 53 trial and alogliptin (Nesina) in the EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial.

Although powered to show superiority of lixisenatide versus placebo in terms of cardiovascular safety, ELIXA was only able to establish noninferiority (HR, 1.02), but results were below limits for noninferiority set by the United States Food and Drug Administration, Dr. Lewis observed. In the updated analysis of ELIXA there was no difference between treatment with the lixisenatide and placebo for the primary composite cardiovascular endpoint plus heart failure hospitalization (hazard ratio, 0.97, 95% confidence interval 0.85-1.10) after 3 years of follow-up. There were also no differences in the rates of heart failure hospitalization (HR, 0.96, 95% CI 0.75-1.23), the primary endpoint plus heart failure hospitalization and coronary revascularization (HR=1.00, 95% CI 0.90-1.11), or death from any cause (HR, 0.94, 95% CI 0.78-1.13).Although the risk for heart failure hospitalization was found to be nine times higher in patients who had a prior history of heart failure in ELIXA than in those who did not there was there was no difference between treatment with the GLP-1 agonist or placebo in patients with (9.7% vs. 10.2%, HR, 0.93, 95% CI 0.66-1.30) or without (2.4% vs. 2.5%, HR, 0.97, 95% CI 0.67-1.40) a history of the disease.

The primary findings of TECOS have been published (doi:10.1056/NEJMoa1501352) and showed sitagliptin to be noninferior to placebo for the primary composite cardiovascular endpoint (HR,0.98; 95% CI, 0.88-1.09; P less than .001). Heart failure hospitalization rates were similar (HR, 1.00; 95% CI, 0.83-1.20; P = .98).

In the updated analysis of TECOS, the prespecified secondary endpoint of time to first hospitalization for heart failure did not differ between the placebo and sitagliptin arms (HR, 1.0; 95% CI, 0.84-1.20, P = .95), nor were there any differences between the treatments in terms of other prespecified secondary endpoints of hospitalization for heart failure or cardiovascular death (HR, 1.02, 95% CI 0.90-1.14, P =.74), or hospitalization for heart failure or all-cause death (HR, 1.00, 95% CI 0.90-1.11, P = .93).

Dr. Armstrong acknowledged that the findings of TECOS were in contrast to the SAVOR-TIMI 53 and EXAMINE trials but that this could be due to several factors: differences in the patients enrolled, the background care provided, and variation in the acquisition or definition of heart failure events between the trials. It could also be due to intrinsic differences among the DPP-4 inhibitors themselves or “chance.”

Dr. Gabriel Steg of Hôpital Bichat in Paris, France who provided independent comment after the presentation of the ELIXA data questioned the value of continuing to perform large-scale noninferiority studies assessing the cardiovascular safety of novel diabetes medicines. More than 150,000 patients have been studied in such trials to date which have shown noninferiority for cardiovascular outcomes.

“Non-inferiority trials are often mistakenly being interpreted as ‘lack of efficacy’ trials and can among nonspecialists generate skepticism regarding treatment of diabetes or the need to control glycemia,” he said. “My conclusion would be to suggest that it is time to stop wasting resources on noninferiority trials and to work on truly improving diabetes care.”

ELXIA was sponsored by Sanofi. Dr. Lewis disclosed receiving research funding from Sanofi, and other drug companies. TECOS was sponsored by Merck. Dr. Armstrong disclosed receiving research funding, educational grants and consulting fees from Merck as well as other companies. Dr. Steg had received research grants from and has acted as a consultant for Sanofi, Merck, and other companies.

LONDON – More than half of all patients hospitalized for heart failure were readmitted within 1 year of discharge in a large Italian population-based study.

Results from the ARNO-CORE CardioVascular Observatory database showed that 56.6% of 41,417 patients with heart failure who were discharged alive and prescribed at least one drug for heart failure were readmitted to the hospital at least once in the following year, Dr. Aldo Maggioni said at the annual congress of the European Society of Cardiology.

Sara Freeman/Frontline Medical News

This averaged out to 2.1 readmissions per person, and importantly, those readmissions were frequently for noncardiovascular reasons, he said. Indeed, 23,826 (49.1%) of rehospitalizations were due to respiratory disease, gastrointestinal disease, cancer, trauma, or other reasons.

“This clearly implies that if we want to impact the total burden of [heart failure], we are not to just consider the reduction in hospitalization for heart failure, but we have to take into account the multiplicity of causes that these patients have,” commented Dr. Maggioni of the National Association of Hospital Cardiologists Research Center in Florence, Italy.

The ARNO-CORE CardioVascular Observatory is a large, retrospective observational study looking at the clinical epidemiology of patients with heart failure. Unlike clinical trial populations and even specialty-run heart failure registries, the ARNO database aims to provide a more representative picture of heart failure and its treatment in a routine practice setting, Dr. Maggioni noted.

Of the 41,413 patients with acute heart failure during 2008-2012 included in the present analysis, just over one-quarter (27%) were admitted to a cardiology unit, with the majority (50%) admitted to internal medicine or general medicine practices, and 14% seen in geriatric departments, 2% in functional recovery or rehabilitation units, 2% in pulmonary units, and the remainder in other practices.

The mean age of patients was 78 years, which was older than that seen in heart failure trials such as the RELAX-AHF study (72 years) and the ESC-HF Long-Term Registry(71 years). There was also a higher percentage of women, compared with the percentage for the trial and the other registry population (51% vs. 38% and 27%, respectively), and there were higher incidences of chronic obstructive pulmonary disease (31% vs. 16% and 20%) and depression (21% in the ARNO population vs. 8% in the ESC-HF Long-Term Registry). A substantial percentage (31%) had diabetes (48% in RELAX-AHF and 39% in the ESC registry), but a lower percentage was found to have coexistent chronic kidney disease (4% vs. 26% in the ESC registry). The reason for the latter difference was perhaps that it was possible to more accurately include only those patients with chronic kidney disease using the administrative coding, Dr. Maggioni said.

In terms of pharmacologic treatments, fewer patients treated in routine practice than in the clinical trial or ESC registry settings received guideline-recommended therapies. Two-thirds (66%) of patients in the ARNO database were taking ACE inhibitors or angiotensin II receptor blockers (ARBs), compared with 72% and 77% of the RELAX-AHF and ESC registry populations. Furthermore only about half (52%) were taking beta-blockers, compared with 89% and 72% of the trial and other ESC registry populations.

Importantly, patients were being treated with suboptimal doses, he said, and adherence rates at 1 year were 58% for ACE inhibitors and ARBs and 62% for beta-blockers.

All-cause mortality at 1 year was 28.7%, which was higher than that seen in clinical studies such as EVEREST (26.1%) and at 6 months in the RELAX-AHF study (9.2%). It was also slightly higher than that seen in the ESC-HF Long-Term Registry (23.6%).

“The yearly cost for a patient with heart failure is high and mainly driven by hospitalizations,” Dr. Maggioni said. The estimated costs per patient per year were $13,295.04, which is higher than that for cardiovascular disease in general ($10,689.59) and lower than for acute coronary syndrome ($16,664.74). Of this cost, roughly 83% is linked to hospitalization and less than 10% to medications and 7% to specialist diagnostic procedures.

“Given the poor prognosis and the high health care costs associated with hospital readmissions, even small improvements in the global heart failure patient care can have a substantial impact on patient quality of life and health care costs,” Dr. Maggioni suggested. He added that better adherence to guideline-recommended medications could also play a vital role.The study was partially supported by Novartis Pharma Italy. Dr. Maggioni disclosed serving on committees of heart failure trials sponsored by Bayer Healthcare, Cardiorentis, and Novartis Pharma Italy.

*This story was updated 9/10/2015.

LONDON – More than half of all patients hospitalized for heart failure were readmitted within 1 year of discharge in a large Italian population-based study.

Results from the ARNO-CORE CardioVascular Observatory database showed that 56.6% of 41,417 patients with heart failure who were discharged alive and prescribed at least one drug for heart failure were readmitted to the hospital at least once in the following year, Dr. Aldo Maggioni said at the annual congress of the European Society of Cardiology.

Sara Freeman/Frontline Medical News

This averaged out to 2.1 readmissions per person, and importantly, those readmissions were frequently for noncardiovascular reasons, he said. Indeed, 23,826 (49.1%) of rehospitalizations were due to respiratory disease, gastrointestinal disease, cancer, trauma, or other reasons.

“This clearly implies that if we want to impact the total burden of [heart failure], we are not to just consider the reduction in hospitalization for heart failure, but we have to take into account the multiplicity of causes that these patients have,” commented Dr. Maggioni of the National Association of Hospital Cardiologists Research Center in Florence, Italy.

The ARNO-CORE CardioVascular Observatory is a large, retrospective observational study looking at the clinical epidemiology of patients with heart failure. Unlike clinical trial populations and even specialty-run heart failure registries, the ARNO database aims to provide a more representative picture of heart failure and its treatment in a routine practice setting, Dr. Maggioni noted.

Of the 41,413 patients with acute heart failure during 2008-2012 included in the present analysis, just over one-quarter (27%) were admitted to a cardiology unit, with the majority (50%) admitted to internal medicine or general medicine practices, and 14% seen in geriatric departments, 2% in functional recovery or rehabilitation units, 2% in pulmonary units, and the remainder in other practices.

The mean age of patients was 78 years, which was older than that seen in heart failure trials such as the RELAX-AHF study (72 years) and the ESC-HF Long-Term Registry(71 years). There was also a higher percentage of women, compared with the percentage for the trial and the other registry population (51% vs. 38% and 27%, respectively), and there were higher incidences of chronic obstructive pulmonary disease (31% vs. 16% and 20%) and depression (21% in the ARNO population vs. 8% in the ESC-HF Long-Term Registry). A substantial percentage (31%) had diabetes (48% in RELAX-AHF and 39% in the ESC registry), but a lower percentage was found to have coexistent chronic kidney disease (4% vs. 26% in the ESC registry). The reason for the latter difference was perhaps that it was possible to more accurately include only those patients with chronic kidney disease using the administrative coding, Dr. Maggioni said.

In terms of pharmacologic treatments, fewer patients treated in routine practice than in the clinical trial or ESC registry settings received guideline-recommended therapies. Two-thirds (66%) of patients in the ARNO database were taking ACE inhibitors or angiotensin II receptor blockers (ARBs), compared with 72% and 77% of the RELAX-AHF and ESC registry populations. Furthermore only about half (52%) were taking beta-blockers, compared with 89% and 72% of the trial and other ESC registry populations.

Importantly, patients were being treated with suboptimal doses, he said, and adherence rates at 1 year were 58% for ACE inhibitors and ARBs and 62% for beta-blockers.

All-cause mortality at 1 year was 28.7%, which was higher than that seen in clinical studies such as EVEREST (26.1%) and at 6 months in the RELAX-AHF study (9.2%). It was also slightly higher than that seen in the ESC-HF Long-Term Registry (23.6%).

“The yearly cost for a patient with heart failure is high and mainly driven by hospitalizations,” Dr. Maggioni said. The estimated costs per patient per year were $13,295.04, which is higher than that for cardiovascular disease in general ($10,689.59) and lower than for acute coronary syndrome ($16,664.74). Of this cost, roughly 83% is linked to hospitalization and less than 10% to medications and 7% to specialist diagnostic procedures.

“Given the poor prognosis and the high health care costs associated with hospital readmissions, even small improvements in the global heart failure patient care can have a substantial impact on patient quality of life and health care costs,” Dr. Maggioni suggested. He added that better adherence to guideline-recommended medications could also play a vital role.The study was partially supported by Novartis Pharma Italy. Dr. Maggioni disclosed serving on committees of heart failure trials sponsored by Bayer Healthcare, Cardiorentis, and Novartis Pharma Italy.

*This story was updated 9/10/2015.

LONDON – More than half of all patients hospitalized for heart failure were readmitted within 1 year of discharge in a large Italian population-based study.

Results from the ARNO-CORE CardioVascular Observatory database showed that 56.6% of 41,417 patients with heart failure who were discharged alive and prescribed at least one drug for heart failure were readmitted to the hospital at least once in the following year, Dr. Aldo Maggioni said at the annual congress of the European Society of Cardiology.

Sara Freeman/Frontline Medical News

This averaged out to 2.1 readmissions per person, and importantly, those readmissions were frequently for noncardiovascular reasons, he said. Indeed, 23,826 (49.1%) of rehospitalizations were due to respiratory disease, gastrointestinal disease, cancer, trauma, or other reasons.

“This clearly implies that if we want to impact the total burden of [heart failure], we are not to just consider the reduction in hospitalization for heart failure, but we have to take into account the multiplicity of causes that these patients have,” commented Dr. Maggioni of the National Association of Hospital Cardiologists Research Center in Florence, Italy.

The ARNO-CORE CardioVascular Observatory is a large, retrospective observational study looking at the clinical epidemiology of patients with heart failure. Unlike clinical trial populations and even specialty-run heart failure registries, the ARNO database aims to provide a more representative picture of heart failure and its treatment in a routine practice setting, Dr. Maggioni noted.

Of the 41,413 patients with acute heart failure during 2008-2012 included in the present analysis, just over one-quarter (27%) were admitted to a cardiology unit, with the majority (50%) admitted to internal medicine or general medicine practices, and 14% seen in geriatric departments, 2% in functional recovery or rehabilitation units, 2% in pulmonary units, and the remainder in other practices.

The mean age of patients was 78 years, which was older than that seen in heart failure trials such as the RELAX-AHF study (72 years) and the ESC-HF Long-Term Registry(71 years). There was also a higher percentage of women, compared with the percentage for the trial and the other registry population (51% vs. 38% and 27%, respectively), and there were higher incidences of chronic obstructive pulmonary disease (31% vs. 16% and 20%) and depression (21% in the ARNO population vs. 8% in the ESC-HF Long-Term Registry). A substantial percentage (31%) had diabetes (48% in RELAX-AHF and 39% in the ESC registry), but a lower percentage was found to have coexistent chronic kidney disease (4% vs. 26% in the ESC registry). The reason for the latter difference was perhaps that it was possible to more accurately include only those patients with chronic kidney disease using the administrative coding, Dr. Maggioni said.

In terms of pharmacologic treatments, fewer patients treated in routine practice than in the clinical trial or ESC registry settings received guideline-recommended therapies. Two-thirds (66%) of patients in the ARNO database were taking ACE inhibitors or angiotensin II receptor blockers (ARBs), compared with 72% and 77% of the RELAX-AHF and ESC registry populations. Furthermore only about half (52%) were taking beta-blockers, compared with 89% and 72% of the trial and other ESC registry populations.

Importantly, patients were being treated with suboptimal doses, he said, and adherence rates at 1 year were 58% for ACE inhibitors and ARBs and 62% for beta-blockers.

All-cause mortality at 1 year was 28.7%, which was higher than that seen in clinical studies such as EVEREST (26.1%) and at 6 months in the RELAX-AHF study (9.2%). It was also slightly higher than that seen in the ESC-HF Long-Term Registry (23.6%).

“The yearly cost for a patient with heart failure is high and mainly driven by hospitalizations,” Dr. Maggioni said. The estimated costs per patient per year were $13,295.04, which is higher than that for cardiovascular disease in general ($10,689.59) and lower than for acute coronary syndrome ($16,664.74). Of this cost, roughly 83% is linked to hospitalization and less than 10% to medications and 7% to specialist diagnostic procedures.

“Given the poor prognosis and the high health care costs associated with hospital readmissions, even small improvements in the global heart failure patient care can have a substantial impact on patient quality of life and health care costs,” Dr. Maggioni suggested. He added that better adherence to guideline-recommended medications could also play a vital role.The study was partially supported by Novartis Pharma Italy. Dr. Maggioni disclosed serving on committees of heart failure trials sponsored by Bayer Healthcare, Cardiorentis, and Novartis Pharma Italy.

*This story was updated 9/10/2015.

LONDON – Heart failure patients who are candidates for cardiac resynchronization therapy in a routine clinical practice setting will likely not benefit from the addition of a defibrillator to a pacemaker, according to results of the CERTITUDE cohort study.

In CERTITUDE, most of the deaths in patients fitted with a cardiac resynchronization therapy–pacemaker (CRT-P) device were predominantly from causes other than sudden cardiac death (SCD), which is the main rationale for using a CRT-defibrillator (CRT-D) device, said lead investigator Jean-Yves Le Heuzey at the annual congress of the European Society of Cardiology.

Sara Freeman/Frontline Medical News

“Our results should not be interpreted as a general lack of benefit from CRT-D vs. CRT-P or vice versa. Rather we demonstrate that given currently selected CRT-P patients in the French population, addition of a defibrillator may not significantly add to survival.” Therefore, patients who may be eligible for CRT should not “automatically” be considered as requiring a CRT-D, suggested Dr. Le Heuzey and his coinvestigators in an article that was published online at the time of the study’s presentation (Eur Heart J. 2015 Sep 1. doi: 10.1093/eurheartj/ehv455).

Current ESC guidelines on cardiac pacing and cardiac resynchronization therapy “leave flexibility for the physician” on the use of CRT-P and CRT-D” because there was no evidence of a superior effect of the latter over CRT alone, said Dr. Le Heuzey of René Descartes University in Paris at the meeting. A randomized, controlled trial would be the only way to determine this, but such a trial is unlikely to ever be conducted, he noted.

Despite the lack of evidence, however, CRT-D is widely used, more so in the United States than in Europe, Dr. Le Heuzey observed, where more than 90% of patients needing CRT would likely have a CRT-D rather than a CRT-P device implanted.

The aims of the CERTITUDE cohort study were to look at the extent to which CRT-P patients differ from CRT-D patients in a real-life setting, and to also see if there were patients in the CRT-P group that might have benefited from CRT-D.

The prospective, observational study involved 1,705 patients who were recruited at 41 centers throughout France over a 2-year period starting in January 2008. Of these, 31% were fitted with a CRT-P device and 69% with a CRT-D.

Results showed that patients who had a CRT-P versus a CRT-D implanted were significantly older, more often female, and more symptomatic. They were also significantly less likely to have coronary artery disease, more likely to have wider QRS intervals and to have atrial fibrillation, and more often had at least two comorbidities.

Analysis of the causes of death was performed at 2 years’ follow-up, which Dr. Le Heuzey conceded was a short period of time. At this point, 267 of 1,611 patients with complete follow-up data had died, giving an overall mortality rate of 8.4% per 100 patient-years for the entire cohort.

The crude mortality rate was found to be higher among CRT-P than CRT-D patients, at 13.1% versus 6.5% per 100 patient-years (relative risk, 2.01; 95% confidence interval, 1.56-2.58; P less than .0001). But when the cause of death was examined more closely, there was no significant difference in the number of SCDs between the groups (RR, 1.57; 95% CI, 0.71-3.46; P = .42) and no significant difference when a specific cause of death analysis was performed.

The main reasons for the almost doubled risk of death in the CRT-P group was an increase in non-SCD cardiovascular mortality, mainly progressive heart failure (RR, 0.27; 95% CI, 1.62-3.18) and other cardiovascular causes (RR, 4.4; 95% CI, 1.29-15.03), Dr. Le Heuzey and associates noted in the article.

“Overall, 95% of the excess mortality among CRT-P recipients was not related to SCD,” they wrote, noting that this “suggests that the presence of a back-up defibrillator would probably not have been beneficial in terms of improving survival for these patients.”

So where does this leave clinicians? Dr. Le Heuzey referred to Table 17 in the European guidelines (Eur Heart J. 2013;34:2281-2329) with guidance on factors favoring CRT-P or CRT-D. For instance, CRT-P might be favorable in a patient with advanced heart failure or one with severe renal insufficiency or on dialysis. Other major comorbidities or frailty or cachexia might veer a decision towards CRT without a defibrillator. On the other hand, factors favoring CRT-D include a life expectancy of more than 1 year; stable, moderate (New York Heart Association class II) disease; or low to moderate–risk ischemic heart disease, with a lack of comorbidities.

CERTITUDE was funded by grants from the French Institute of Health and Medical Research (INSERM) and from the French Cardiology Society. The latter received specific grants from Biotronik, Boston Scientific, Medtronic, Saint Jude Medical, and Sorin in order to perform the study. Dr. Le Heuzey disclosed receiving fees for participation in advisory boards and conferences from AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb/Pfizer, Correvio, Daiichi-Sankyo, Meda, Sanofi, and Servier.

LONDON – Heart failure patients who are candidates for cardiac resynchronization therapy in a routine clinical practice setting will likely not benefit from the addition of a defibrillator to a pacemaker, according to results of the CERTITUDE cohort study.

In CERTITUDE, most of the deaths in patients fitted with a cardiac resynchronization therapy–pacemaker (CRT-P) device were predominantly from causes other than sudden cardiac death (SCD), which is the main rationale for using a CRT-defibrillator (CRT-D) device, said lead investigator Jean-Yves Le Heuzey at the annual congress of the European Society of Cardiology.

Sara Freeman/Frontline Medical News

“Our results should not be interpreted as a general lack of benefit from CRT-D vs. CRT-P or vice versa. Rather we demonstrate that given currently selected CRT-P patients in the French population, addition of a defibrillator may not significantly add to survival.” Therefore, patients who may be eligible for CRT should not “automatically” be considered as requiring a CRT-D, suggested Dr. Le Heuzey and his coinvestigators in an article that was published online at the time of the study’s presentation (Eur Heart J. 2015 Sep 1. doi: 10.1093/eurheartj/ehv455).

Current ESC guidelines on cardiac pacing and cardiac resynchronization therapy “leave flexibility for the physician” on the use of CRT-P and CRT-D” because there was no evidence of a superior effect of the latter over CRT alone, said Dr. Le Heuzey of René Descartes University in Paris at the meeting. A randomized, controlled trial would be the only way to determine this, but such a trial is unlikely to ever be conducted, he noted.

Despite the lack of evidence, however, CRT-D is widely used, more so in the United States than in Europe, Dr. Le Heuzey observed, where more than 90% of patients needing CRT would likely have a CRT-D rather than a CRT-P device implanted.

The aims of the CERTITUDE cohort study were to look at the extent to which CRT-P patients differ from CRT-D patients in a real-life setting, and to also see if there were patients in the CRT-P group that might have benefited from CRT-D.

The prospective, observational study involved 1,705 patients who were recruited at 41 centers throughout France over a 2-year period starting in January 2008. Of these, 31% were fitted with a CRT-P device and 69% with a CRT-D.

Results showed that patients who had a CRT-P versus a CRT-D implanted were significantly older, more often female, and more symptomatic. They were also significantly less likely to have coronary artery disease, more likely to have wider QRS intervals and to have atrial fibrillation, and more often had at least two comorbidities.

Analysis of the causes of death was performed at 2 years’ follow-up, which Dr. Le Heuzey conceded was a short period of time. At this point, 267 of 1,611 patients with complete follow-up data had died, giving an overall mortality rate of 8.4% per 100 patient-years for the entire cohort.

The crude mortality rate was found to be higher among CRT-P than CRT-D patients, at 13.1% versus 6.5% per 100 patient-years (relative risk, 2.01; 95% confidence interval, 1.56-2.58; P less than .0001). But when the cause of death was examined more closely, there was no significant difference in the number of SCDs between the groups (RR, 1.57; 95% CI, 0.71-3.46; P = .42) and no significant difference when a specific cause of death analysis was performed.

The main reasons for the almost doubled risk of death in the CRT-P group was an increase in non-SCD cardiovascular mortality, mainly progressive heart failure (RR, 0.27; 95% CI, 1.62-3.18) and other cardiovascular causes (RR, 4.4; 95% CI, 1.29-15.03), Dr. Le Heuzey and associates noted in the article.

“Overall, 95% of the excess mortality among CRT-P recipients was not related to SCD,” they wrote, noting that this “suggests that the presence of a back-up defibrillator would probably not have been beneficial in terms of improving survival for these patients.”

So where does this leave clinicians? Dr. Le Heuzey referred to Table 17 in the European guidelines (Eur Heart J. 2013;34:2281-2329) with guidance on factors favoring CRT-P or CRT-D. For instance, CRT-P might be favorable in a patient with advanced heart failure or one with severe renal insufficiency or on dialysis. Other major comorbidities or frailty or cachexia might veer a decision towards CRT without a defibrillator. On the other hand, factors favoring CRT-D include a life expectancy of more than 1 year; stable, moderate (New York Heart Association class II) disease; or low to moderate–risk ischemic heart disease, with a lack of comorbidities.

CERTITUDE was funded by grants from the French Institute of Health and Medical Research (INSERM) and from the French Cardiology Society. The latter received specific grants from Biotronik, Boston Scientific, Medtronic, Saint Jude Medical, and Sorin in order to perform the study. Dr. Le Heuzey disclosed receiving fees for participation in advisory boards and conferences from AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb/Pfizer, Correvio, Daiichi-Sankyo, Meda, Sanofi, and Servier.

LONDON – Heart failure patients who are candidates for cardiac resynchronization therapy in a routine clinical practice setting will likely not benefit from the addition of a defibrillator to a pacemaker, according to results of the CERTITUDE cohort study.

In CERTITUDE, most of the deaths in patients fitted with a cardiac resynchronization therapy–pacemaker (CRT-P) device were predominantly from causes other than sudden cardiac death (SCD), which is the main rationale for using a CRT-defibrillator (CRT-D) device, said lead investigator Jean-Yves Le Heuzey at the annual congress of the European Society of Cardiology.

Sara Freeman/Frontline Medical News

“Our results should not be interpreted as a general lack of benefit from CRT-D vs. CRT-P or vice versa. Rather we demonstrate that given currently selected CRT-P patients in the French population, addition of a defibrillator may not significantly add to survival.” Therefore, patients who may be eligible for CRT should not “automatically” be considered as requiring a CRT-D, suggested Dr. Le Heuzey and his coinvestigators in an article that was published online at the time of the study’s presentation (Eur Heart J. 2015 Sep 1. doi: 10.1093/eurheartj/ehv455).

Current ESC guidelines on cardiac pacing and cardiac resynchronization therapy “leave flexibility for the physician” on the use of CRT-P and CRT-D” because there was no evidence of a superior effect of the latter over CRT alone, said Dr. Le Heuzey of René Descartes University in Paris at the meeting. A randomized, controlled trial would be the only way to determine this, but such a trial is unlikely to ever be conducted, he noted.

Despite the lack of evidence, however, CRT-D is widely used, more so in the United States than in Europe, Dr. Le Heuzey observed, where more than 90% of patients needing CRT would likely have a CRT-D rather than a CRT-P device implanted.

The aims of the CERTITUDE cohort study were to look at the extent to which CRT-P patients differ from CRT-D patients in a real-life setting, and to also see if there were patients in the CRT-P group that might have benefited from CRT-D.

The prospective, observational study involved 1,705 patients who were recruited at 41 centers throughout France over a 2-year period starting in January 2008. Of these, 31% were fitted with a CRT-P device and 69% with a CRT-D.

Results showed that patients who had a CRT-P versus a CRT-D implanted were significantly older, more often female, and more symptomatic. They were also significantly less likely to have coronary artery disease, more likely to have wider QRS intervals and to have atrial fibrillation, and more often had at least two comorbidities.

Analysis of the causes of death was performed at 2 years’ follow-up, which Dr. Le Heuzey conceded was a short period of time. At this point, 267 of 1,611 patients with complete follow-up data had died, giving an overall mortality rate of 8.4% per 100 patient-years for the entire cohort.

The crude mortality rate was found to be higher among CRT-P than CRT-D patients, at 13.1% versus 6.5% per 100 patient-years (relative risk, 2.01; 95% confidence interval, 1.56-2.58; P less than .0001). But when the cause of death was examined more closely, there was no significant difference in the number of SCDs between the groups (RR, 1.57; 95% CI, 0.71-3.46; P = .42) and no significant difference when a specific cause of death analysis was performed.

The main reasons for the almost doubled risk of death in the CRT-P group was an increase in non-SCD cardiovascular mortality, mainly progressive heart failure (RR, 0.27; 95% CI, 1.62-3.18) and other cardiovascular causes (RR, 4.4; 95% CI, 1.29-15.03), Dr. Le Heuzey and associates noted in the article.

“Overall, 95% of the excess mortality among CRT-P recipients was not related to SCD,” they wrote, noting that this “suggests that the presence of a back-up defibrillator would probably not have been beneficial in terms of improving survival for these patients.”

So where does this leave clinicians? Dr. Le Heuzey referred to Table 17 in the European guidelines (Eur Heart J. 2013;34:2281-2329) with guidance on factors favoring CRT-P or CRT-D. For instance, CRT-P might be favorable in a patient with advanced heart failure or one with severe renal insufficiency or on dialysis. Other major comorbidities or frailty or cachexia might veer a decision towards CRT without a defibrillator. On the other hand, factors favoring CRT-D include a life expectancy of more than 1 year; stable, moderate (New York Heart Association class II) disease; or low to moderate–risk ischemic heart disease, with a lack of comorbidities.

CERTITUDE was funded by grants from the French Institute of Health and Medical Research (INSERM) and from the French Cardiology Society. The latter received specific grants from Biotronik, Boston Scientific, Medtronic, Saint Jude Medical, and Sorin in order to perform the study. Dr. Le Heuzey disclosed receiving fees for participation in advisory boards and conferences from AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb/Pfizer, Correvio, Daiichi-Sankyo, Meda, Sanofi, and Servier.

LONDON – Ticagrelor was associated with fewer major bleeding complications compared with clopidogrel when stopped before revascularization surgery, in a large observational study that included all patients on dual antiplatelet therapy who underwent bypass surgery over a 2-year period in Sweden.

The overall incidence of major bleeding was 12.9% and 17.6%, respectively, when these antiplatelet agents were stopped before coronary artery bypass grafting (CABG). The adjusted odds ratio (OR) was 0.72, representing a 28% lower incidence with ticagrelor than with clopidogrel (P = .012).The study findings indicated that it might be safe to stop ticagrelor but not clopidogrel slightly closer to the procedure than is currently recommended by European (Eur Heart J. 2014;35:2541-2619) and American (J Am Coll Cardiol. 2013;61:e179-e347) guidelines.

“The overall incidence of major CABG-related bleeding complications was lower with ticagrelor than with clopidogrel,” Dr. Anders Jeppsson said at the annual meeting of the European Society of Cardiology.

“The difference was mainly driven by a lower incidence when clopidogrel and ticagrelor were discontinued 72 to 120 hours before surgery,” he added.

Dr. Jeppsson of Sahlgrenska (Sweden) University Hospital and the University of Gothenburg noted that the incidence of CABG-related major bleeding was highest for both antiplatelet agents when they were stopped less than 24 hours before surgery but that there was no significant difference between the two antiplatelet agents.

“Discontinuation of ticagrelor 3 days before CABG, as opposed to 5 days, did not increase the incidence of major bleeding complications,” he reported. The OR for discontinuing ticagrelor at 72-120 hours versus more than 120 hours before surgery was 0.93 (P = .08). However, the situation was not the same for discontinuing clopidogrel, with a higher rate of bleeding when the drug was discontinued closer to surgery (OR = 1.17, P = .033).

The findings, which were published online Sept. 1 in the European Heart Journal (doi:10.1093/eurheartj/ehv381), come from an analysis of data prospectively obtained from the SWEDEHEART registry and other local Swedish registries, databases, and patient records. Dr. Jeppsson explained that the aims were to compare the incidence of CABG-related bleeding complications among patients with acute coronary syndromes (ACS) who were taking dual antiplatelet therapy with aspirin and either clopidogrel or ticagrelor in a real-world setting and to see if shorter discontinuation periods before surgery might be feasible.

“A short discontinuation time would reduce the risk for thrombotic events while waiting [for surgery] and save hospital resources,” Dr. Jeppsson said. “But on the other hand it may increase the risk for bleeding complications.”

Data from January 2012 to December 2013 were obtained on all patients in Sweden who were taking dual antiplatelet therapy before CABG. This time period was chosen as it was when ticagrelor was first introduced for the first-line treatment of ACS in the country. Of 2,418 patients identified, 10 were taking prasugrel and were excluded from the analysis. A further 164 patients were excluded as they had discontinued dual antiplatelet therapy more than 2 weeks before having surgery, leaving 1,266 patients who had received ticagrelor and 978 who had been taking clopidogrel.The Bleeding Academic Research Consortium (BARC) Type 4 definition (Circulation. 2011;123:2736-47) was primarily used to identify CABG-related bleeding, with three other published definitions also used, including those used in the BART (N Engl J Med. 2008;358:2319-31) and PLATO (N Engl J Med. 2009;361:1045-57) antiplatelet trials.The overall incidence of major bleeding complications was significantly lower with ticagrelor versus clopidogrel using all four of the bleeding definitions.

However, discontinuing ticagrelor 24 hours or less before CABG showed that while there was a similar amount of BARC major bleeding (P = .052) compared with stopping clopidogrel, the median amount of blood loss (P less than .001), need for red blood cell (P = .028) or platelet (P less than .001) transfusion was greater.To illustrate the dangers of major bleeding on patient outcome, Dr. Jeppsson noted that patients who experienced major bleeding were almost 15 times more likely to die 30 days after the procedure than were those who had no major bleeding. The 30-day mortality rate was higher in clopidogrel than ticagrelor-treated patients (2.7% vs 1.7%) and incidence of thrombotic events was 2.8% and 2.3% These are unadjusted findings and the study was not statistically powered to look at these as end points, Dr. Jeppsson emphasized. These factors were registered for safety reasons, he said.

The study was supported by an investigator-sponsored study program of AstraZeneca and the Swedish Heart and Lung Foundation. Dr. Jeppsson has received research grants, consulting fees or speaker’s honorarium from AstraZeneca in addition to several other pharmaceutical companies.

LONDON – Ticagrelor was associated with fewer major bleeding complications compared with clopidogrel when stopped before revascularization surgery, in a large observational study that included all patients on dual antiplatelet therapy who underwent bypass surgery over a 2-year period in Sweden.

The overall incidence of major bleeding was 12.9% and 17.6%, respectively, when these antiplatelet agents were stopped before coronary artery bypass grafting (CABG). The adjusted odds ratio (OR) was 0.72, representing a 28% lower incidence with ticagrelor than with clopidogrel (P = .012).The study findings indicated that it might be safe to stop ticagrelor but not clopidogrel slightly closer to the procedure than is currently recommended by European (Eur Heart J. 2014;35:2541-2619) and American (J Am Coll Cardiol. 2013;61:e179-e347) guidelines.

“The overall incidence of major CABG-related bleeding complications was lower with ticagrelor than with clopidogrel,” Dr. Anders Jeppsson said at the annual meeting of the European Society of Cardiology.

“The difference was mainly driven by a lower incidence when clopidogrel and ticagrelor were discontinued 72 to 120 hours before surgery,” he added.

Dr. Jeppsson of Sahlgrenska (Sweden) University Hospital and the University of Gothenburg noted that the incidence of CABG-related major bleeding was highest for both antiplatelet agents when they were stopped less than 24 hours before surgery but that there was no significant difference between the two antiplatelet agents.

“Discontinuation of ticagrelor 3 days before CABG, as opposed to 5 days, did not increase the incidence of major bleeding complications,” he reported. The OR for discontinuing ticagrelor at 72-120 hours versus more than 120 hours before surgery was 0.93 (P = .08). However, the situation was not the same for discontinuing clopidogrel, with a higher rate of bleeding when the drug was discontinued closer to surgery (OR = 1.17, P = .033).

The findings, which were published online Sept. 1 in the European Heart Journal (doi:10.1093/eurheartj/ehv381), come from an analysis of data prospectively obtained from the SWEDEHEART registry and other local Swedish registries, databases, and patient records. Dr. Jeppsson explained that the aims were to compare the incidence of CABG-related bleeding complications among patients with acute coronary syndromes (ACS) who were taking dual antiplatelet therapy with aspirin and either clopidogrel or ticagrelor in a real-world setting and to see if shorter discontinuation periods before surgery might be feasible.

“A short discontinuation time would reduce the risk for thrombotic events while waiting [for surgery] and save hospital resources,” Dr. Jeppsson said. “But on the other hand it may increase the risk for bleeding complications.”

Data from January 2012 to December 2013 were obtained on all patients in Sweden who were taking dual antiplatelet therapy before CABG. This time period was chosen as it was when ticagrelor was first introduced for the first-line treatment of ACS in the country. Of 2,418 patients identified, 10 were taking prasugrel and were excluded from the analysis. A further 164 patients were excluded as they had discontinued dual antiplatelet therapy more than 2 weeks before having surgery, leaving 1,266 patients who had received ticagrelor and 978 who had been taking clopidogrel.The Bleeding Academic Research Consortium (BARC) Type 4 definition (Circulation. 2011;123:2736-47) was primarily used to identify CABG-related bleeding, with three other published definitions also used, including those used in the BART (N Engl J Med. 2008;358:2319-31) and PLATO (N Engl J Med. 2009;361:1045-57) antiplatelet trials.The overall incidence of major bleeding complications was significantly lower with ticagrelor versus clopidogrel using all four of the bleeding definitions.

However, discontinuing ticagrelor 24 hours or less before CABG showed that while there was a similar amount of BARC major bleeding (P = .052) compared with stopping clopidogrel, the median amount of blood loss (P less than .001), need for red blood cell (P = .028) or platelet (P less than .001) transfusion was greater.To illustrate the dangers of major bleeding on patient outcome, Dr. Jeppsson noted that patients who experienced major bleeding were almost 15 times more likely to die 30 days after the procedure than were those who had no major bleeding. The 30-day mortality rate was higher in clopidogrel than ticagrelor-treated patients (2.7% vs 1.7%) and incidence of thrombotic events was 2.8% and 2.3% These are unadjusted findings and the study was not statistically powered to look at these as end points, Dr. Jeppsson emphasized. These factors were registered for safety reasons, he said.

The study was supported by an investigator-sponsored study program of AstraZeneca and the Swedish Heart and Lung Foundation. Dr. Jeppsson has received research grants, consulting fees or speaker’s honorarium from AstraZeneca in addition to several other pharmaceutical companies.

LONDON – Ticagrelor was associated with fewer major bleeding complications compared with clopidogrel when stopped before revascularization surgery, in a large observational study that included all patients on dual antiplatelet therapy who underwent bypass surgery over a 2-year period in Sweden.

The overall incidence of major bleeding was 12.9% and 17.6%, respectively, when these antiplatelet agents were stopped before coronary artery bypass grafting (CABG). The adjusted odds ratio (OR) was 0.72, representing a 28% lower incidence with ticagrelor than with clopidogrel (P = .012).The study findings indicated that it might be safe to stop ticagrelor but not clopidogrel slightly closer to the procedure than is currently recommended by European (Eur Heart J. 2014;35:2541-2619) and American (J Am Coll Cardiol. 2013;61:e179-e347) guidelines.

“The overall incidence of major CABG-related bleeding complications was lower with ticagrelor than with clopidogrel,” Dr. Anders Jeppsson said at the annual meeting of the European Society of Cardiology.

“The difference was mainly driven by a lower incidence when clopidogrel and ticagrelor were discontinued 72 to 120 hours before surgery,” he added.

Dr. Jeppsson of Sahlgrenska (Sweden) University Hospital and the University of Gothenburg noted that the incidence of CABG-related major bleeding was highest for both antiplatelet agents when they were stopped less than 24 hours before surgery but that there was no significant difference between the two antiplatelet agents.

“Discontinuation of ticagrelor 3 days before CABG, as opposed to 5 days, did not increase the incidence of major bleeding complications,” he reported. The OR for discontinuing ticagrelor at 72-120 hours versus more than 120 hours before surgery was 0.93 (P = .08). However, the situation was not the same for discontinuing clopidogrel, with a higher rate of bleeding when the drug was discontinued closer to surgery (OR = 1.17, P = .033).

The findings, which were published online Sept. 1 in the European Heart Journal (doi:10.1093/eurheartj/ehv381), come from an analysis of data prospectively obtained from the SWEDEHEART registry and other local Swedish registries, databases, and patient records. Dr. Jeppsson explained that the aims were to compare the incidence of CABG-related bleeding complications among patients with acute coronary syndromes (ACS) who were taking dual antiplatelet therapy with aspirin and either clopidogrel or ticagrelor in a real-world setting and to see if shorter discontinuation periods before surgery might be feasible.

“A short discontinuation time would reduce the risk for thrombotic events while waiting [for surgery] and save hospital resources,” Dr. Jeppsson said. “But on the other hand it may increase the risk for bleeding complications.”

Data from January 2012 to December 2013 were obtained on all patients in Sweden who were taking dual antiplatelet therapy before CABG. This time period was chosen as it was when ticagrelor was first introduced for the first-line treatment of ACS in the country. Of 2,418 patients identified, 10 were taking prasugrel and were excluded from the analysis. A further 164 patients were excluded as they had discontinued dual antiplatelet therapy more than 2 weeks before having surgery, leaving 1,266 patients who had received ticagrelor and 978 who had been taking clopidogrel.The Bleeding Academic Research Consortium (BARC) Type 4 definition (Circulation. 2011;123:2736-47) was primarily used to identify CABG-related bleeding, with three other published definitions also used, including those used in the BART (N Engl J Med. 2008;358:2319-31) and PLATO (N Engl J Med. 2009;361:1045-57) antiplatelet trials.The overall incidence of major bleeding complications was significantly lower with ticagrelor versus clopidogrel using all four of the bleeding definitions.

However, discontinuing ticagrelor 24 hours or less before CABG showed that while there was a similar amount of BARC major bleeding (P = .052) compared with stopping clopidogrel, the median amount of blood loss (P less than .001), need for red blood cell (P = .028) or platelet (P less than .001) transfusion was greater.To illustrate the dangers of major bleeding on patient outcome, Dr. Jeppsson noted that patients who experienced major bleeding were almost 15 times more likely to die 30 days after the procedure than were those who had no major bleeding. The 30-day mortality rate was higher in clopidogrel than ticagrelor-treated patients (2.7% vs 1.7%) and incidence of thrombotic events was 2.8% and 2.3% These are unadjusted findings and the study was not statistically powered to look at these as end points, Dr. Jeppsson emphasized. These factors were registered for safety reasons, he said.

The study was supported by an investigator-sponsored study program of AstraZeneca and the Swedish Heart and Lung Foundation. Dr. Jeppsson has received research grants, consulting fees or speaker’s honorarium from AstraZeneca in addition to several other pharmaceutical companies.

LONDON – Neither the GLP-1 receptor agonist lixisenatide nor the DPP-4 inhibitor sitagliptin significantly increased the risk of heart failure or associated hospitalizations in patients with type 2 diabetes, according to data from two large cardiovascular safety trials.

Further analysis from ELIXA (Evaluation of Lixisenatide [Lyxumia] in Acute Coronary Syndrome) showed that the hazard ratios for several secondary heart failure endpoints were 1.00 or below. Although the risk for heart failure hospitalization was found to be nine times higher in patients who had a prior history of heart failure than in those who did not, there was there was no difference between treatment with the GLP-1 (glucagon-like peptide 1) agonist or placebo.

The findings add to those already presented in June at the annual scientific sessions of the American Diabetes Association from the 6,068-patient trial, which enrolled patients with type 2 diabetes who had experienced an acute coronary syndrome within the past 6 months.

Other reassuring data on the safety of newer diabetes medicines came from an updated analysis of TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin [Januvia]). The time to first hospitalization for heart failure did not differ between the placebo and sitagliptin arms, and there were no differences between the treatments in terms of hospitalization for heart failure or cardiovascular death or hospitalization for heart failure or all-cause death with the DPP-4 (dipeptyl peptidase 4) inhibitor. TECOS enrolled nearly 15,000 patients with type 2 diabetes and concurrent cardiovascular disease who were aged 50 years or older and the primary findings have been published (N Engl J Med. 2015 July 15;373:232-42).

These trials provide accumulating evidence that there is no heart failure risk with these particular diabetes medications, Dr. Lars Rydén, professor of cardiology at the Karolinska Institute in Stockholm, commented in an interview at the annual congress of the European Society of Cardiology. Dr. Rydén added that the trial results everyone is waiting to hear about concern the cardiovascular safety of the selective sodium–glucose cotransporter-2 (SGLT-2) inhibitor empagliflozin (Jardiance).

Advance information issued by manufacturer Boehringer-Ingelheim suggests that this drug actually may lower cardiovascular risk in patients at high risk for cardiovascular events, Dr. Rydén observed. “Now, if that is true, it is the only modern glucose-lowering drug to have shown such a capacity.” Results of the EMPA-REG OUTCOME study will be presented in September at the annual meeting of the European Association for the Study of Diabetes in Stockholm.

LONDON – Neither the GLP-1 receptor agonist lixisenatide nor the DPP-4 inhibitor sitagliptin significantly increased the risk of heart failure or associated hospitalizations in patients with type 2 diabetes, according to data from two large cardiovascular safety trials.

Further analysis from ELIXA (Evaluation of Lixisenatide [Lyxumia] in Acute Coronary Syndrome) showed that the hazard ratios for several secondary heart failure endpoints were 1.00 or below. Although the risk for heart failure hospitalization was found to be nine times higher in patients who had a prior history of heart failure than in those who did not, there was there was no difference between treatment with the GLP-1 (glucagon-like peptide 1) agonist or placebo.

The findings add to those already presented in June at the annual scientific sessions of the American Diabetes Association from the 6,068-patient trial, which enrolled patients with type 2 diabetes who had experienced an acute coronary syndrome within the past 6 months.

Other reassuring data on the safety of newer diabetes medicines came from an updated analysis of TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin [Januvia]). The time to first hospitalization for heart failure did not differ between the placebo and sitagliptin arms, and there were no differences between the treatments in terms of hospitalization for heart failure or cardiovascular death or hospitalization for heart failure or all-cause death with the DPP-4 (dipeptyl peptidase 4) inhibitor. TECOS enrolled nearly 15,000 patients with type 2 diabetes and concurrent cardiovascular disease who were aged 50 years or older and the primary findings have been published (N Engl J Med. 2015 July 15;373:232-42).

These trials provide accumulating evidence that there is no heart failure risk with these particular diabetes medications, Dr. Lars Rydén, professor of cardiology at the Karolinska Institute in Stockholm, commented in an interview at the annual congress of the European Society of Cardiology. Dr. Rydén added that the trial results everyone is waiting to hear about concern the cardiovascular safety of the selective sodium–glucose cotransporter-2 (SGLT-2) inhibitor empagliflozin (Jardiance).

Advance information issued by manufacturer Boehringer-Ingelheim suggests that this drug actually may lower cardiovascular risk in patients at high risk for cardiovascular events, Dr. Rydén observed. “Now, if that is true, it is the only modern glucose-lowering drug to have shown such a capacity.” Results of the EMPA-REG OUTCOME study will be presented in September at the annual meeting of the European Association for the Study of Diabetes in Stockholm.

LONDON – Neither the GLP-1 receptor agonist lixisenatide nor the DPP-4 inhibitor sitagliptin significantly increased the risk of heart failure or associated hospitalizations in patients with type 2 diabetes, according to data from two large cardiovascular safety trials.

Further analysis from ELIXA (Evaluation of Lixisenatide [Lyxumia] in Acute Coronary Syndrome) showed that the hazard ratios for several secondary heart failure endpoints were 1.00 or below. Although the risk for heart failure hospitalization was found to be nine times higher in patients who had a prior history of heart failure than in those who did not, there was there was no difference between treatment with the GLP-1 (glucagon-like peptide 1) agonist or placebo.

The findings add to those already presented in June at the annual scientific sessions of the American Diabetes Association from the 6,068-patient trial, which enrolled patients with type 2 diabetes who had experienced an acute coronary syndrome within the past 6 months.

Other reassuring data on the safety of newer diabetes medicines came from an updated analysis of TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin [Januvia]). The time to first hospitalization for heart failure did not differ between the placebo and sitagliptin arms, and there were no differences between the treatments in terms of hospitalization for heart failure or cardiovascular death or hospitalization for heart failure or all-cause death with the DPP-4 (dipeptyl peptidase 4) inhibitor. TECOS enrolled nearly 15,000 patients with type 2 diabetes and concurrent cardiovascular disease who were aged 50 years or older and the primary findings have been published (N Engl J Med. 2015 July 15;373:232-42).

These trials provide accumulating evidence that there is no heart failure risk with these particular diabetes medications, Dr. Lars Rydén, professor of cardiology at the Karolinska Institute in Stockholm, commented in an interview at the annual congress of the European Society of Cardiology. Dr. Rydén added that the trial results everyone is waiting to hear about concern the cardiovascular safety of the selective sodium–glucose cotransporter-2 (SGLT-2) inhibitor empagliflozin (Jardiance).

Advance information issued by manufacturer Boehringer-Ingelheim suggests that this drug actually may lower cardiovascular risk in patients at high risk for cardiovascular events, Dr. Rydén observed. “Now, if that is true, it is the only modern glucose-lowering drug to have shown such a capacity.” Results of the EMPA-REG OUTCOME study will be presented in September at the annual meeting of the European Association for the Study of Diabetes in Stockholm.