In the Journals

Ezetimibe produces strongest CV benefit in patients with diabetes

Robert Giugliano
Robert P. Giugliano

Among patients with recent ACS on statin therapy, those with diabetes benefited most from adding ezetimibe vs. those without diabetes, according to new data from the IMPROVE-IT trial.

The treatment effect of ezetimibe (Zetia, Merck) did not differ by diabetes status in patients aged at least 75 years, but patients younger than 75 years had greater benefit with ezetimibe if they had diabetes than if they did not, Robert P. Giugliano, MD, SM, cardiovascular medicine specialist at Brigham and Women’s Hospital and a senior investigator at the Thrombolysis in Myocardial Infarction Study Group, and colleagues reported in Circulation.

The analysis was one of several from IMPROVE-IT presented at the European Society of Cardiology Congress in 2015, as Cardiology Today previously reported.

Giugliano and colleagues analyzed whether there was a difference in treatment effect for ezetimibe plus simvastatin (Vytorin, Merck) vs. placebo plus simvastatin according to diabetes status in the IMPROVE-IT population.

Compared with those without diabetes, the 27% of the 18,144 patients from IMPROVE-IT with diabetes were older, more likely to be women, more likely to have prior MI and revascularization, and more likely to have presented with non-ST segment elevation ACS (P < .001 for all), according to the researchers.

Median LDL at admission was lower in those with diabetes than in those without it (89 mg/dL vs. 97 mg/dL; P < .001). Time-weighted average LDL achieved was lower in those assigned ezetimibe regardless of diabetes status (patients with diabetes: 49 mg/dL vs. 67 mg/dL; patients without diabetes, 55 mg/dL vs. 71 mg/dL; P < .001 for both).

Diabetes status

The absolute reduction in the primary endpoint of CV death, major coronary events and stroke at 7 years conferred by ezetimibe was 5.5% in patients with diabetes (HR = 0.85; 95% CI, 0.78-0.94) but 0.7% in patients without diabetes (HR = 0.98; 95% CI, 0.91-1.04; P for interaction = .02), according to the researchers.

Among those with diabetes, ezetimibe was associated with a 24% RR in MI and a 39% RR in ischemic stroke, they wrote. Safety outcomes did not differ by diabetes status.

In patients aged at least 75 years, ezetimibe was linked to a 20% RR in the primary endpoint, which was consistent regardless of diabetes status (P for interaction = .91). However, Giugliano and colleagues wrote, in patients younger than 75 years, ezetimibe reduced risk for the primary endpoint in those with diabetes (HR = 0.87; 95% CI, 0.78-0.96; number needed to treat = 21; 95% CI, 12-73) but not in those without diabetes (HR = 1.02; 95% CI, 0.95-1.1; P for interaction = .01).

Benefit and risk

In an analysis in which patients were stratified by TIMI risk score for secondary prevention, benefit from ezetimibe was consistent across risk scores in patients with diabetes. However, in patients without diabetes, those with a high risk score had an 18% RR in CV death/MI/ischemic stroke with ezetimibe/simvastatin vs. placebo/simvastatin, but those with a medium or low score had no benefit (P for interaction = .034).

“It would be incorrect to conclude that patients without diabetes experienced no benefit with the addition of ezetimibe,” Giugliano and colleagues wrote. “Although the benefit of adding ezetimibe to simvastatin in patients without [diabetes] was modest overall, among nondiabetic patients who were at high risk for cardiovascular events, either on the basis of advanced age or an elevated risk score, significant reductions in cardiovascular events were observed with [ezetimibe/simvastatin] compared to [placebo/simvastatin].” – by Erik Swain

Disclosures: IMPROVE-IT was sponsored by Merck. Giugliano reports he has financial ties with Amarin, Amgen, Bristol-Myers Squibb, CVS Caremark, Daiichi Sankyo, GlaxoSmithKline, Lexicon, Merck and Pfizer. Please see the study for the other authors’ relevant financial disclosures.

 

 

Robert Giugliano
Robert P. Giugliano

Among patients with recent ACS on statin therapy, those with diabetes benefited most from adding ezetimibe vs. those without diabetes, according to new data from the IMPROVE-IT trial.

The treatment effect of ezetimibe (Zetia, Merck) did not differ by diabetes status in patients aged at least 75 years, but patients younger than 75 years had greater benefit with ezetimibe if they had diabetes than if they did not, Robert P. Giugliano, MD, SM, cardiovascular medicine specialist at Brigham and Women’s Hospital and a senior investigator at the Thrombolysis in Myocardial Infarction Study Group, and colleagues reported in Circulation.

The analysis was one of several from IMPROVE-IT presented at the European Society of Cardiology Congress in 2015, as Cardiology Today previously reported.

Giugliano and colleagues analyzed whether there was a difference in treatment effect for ezetimibe plus simvastatin (Vytorin, Merck) vs. placebo plus simvastatin according to diabetes status in the IMPROVE-IT population.

Compared with those without diabetes, the 27% of the 18,144 patients from IMPROVE-IT with diabetes were older, more likely to be women, more likely to have prior MI and revascularization, and more likely to have presented with non-ST segment elevation ACS (P < .001 for all), according to the researchers.

Median LDL at admission was lower in those with diabetes than in those without it (89 mg/dL vs. 97 mg/dL; P < .001). Time-weighted average LDL achieved was lower in those assigned ezetimibe regardless of diabetes status (patients with diabetes: 49 mg/dL vs. 67 mg/dL; patients without diabetes, 55 mg/dL vs. 71 mg/dL; P < .001 for both).

Diabetes status

The absolute reduction in the primary endpoint of CV death, major coronary events and stroke at 7 years conferred by ezetimibe was 5.5% in patients with diabetes (HR = 0.85; 95% CI, 0.78-0.94) but 0.7% in patients without diabetes (HR = 0.98; 95% CI, 0.91-1.04; P for interaction = .02), according to the researchers.

Among those with diabetes, ezetimibe was associated with a 24% RR in MI and a 39% RR in ischemic stroke, they wrote. Safety outcomes did not differ by diabetes status.

In patients aged at least 75 years, ezetimibe was linked to a 20% RR in the primary endpoint, which was consistent regardless of diabetes status (P for interaction = .91). However, Giugliano and colleagues wrote, in patients younger than 75 years, ezetimibe reduced risk for the primary endpoint in those with diabetes (HR = 0.87; 95% CI, 0.78-0.96; number needed to treat = 21; 95% CI, 12-73) but not in those without diabetes (HR = 1.02; 95% CI, 0.95-1.1; P for interaction = .01).

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Benefit and risk

In an analysis in which patients were stratified by TIMI risk score for secondary prevention, benefit from ezetimibe was consistent across risk scores in patients with diabetes. However, in patients without diabetes, those with a high risk score had an 18% RR in CV death/MI/ischemic stroke with ezetimibe/simvastatin vs. placebo/simvastatin, but those with a medium or low score had no benefit (P for interaction = .034).

“It would be incorrect to conclude that patients without diabetes experienced no benefit with the addition of ezetimibe,” Giugliano and colleagues wrote. “Although the benefit of adding ezetimibe to simvastatin in patients without [diabetes] was modest overall, among nondiabetic patients who were at high risk for cardiovascular events, either on the basis of advanced age or an elevated risk score, significant reductions in cardiovascular events were observed with [ezetimibe/simvastatin] compared to [placebo/simvastatin].” – by Erik Swain

Disclosures: IMPROVE-IT was sponsored by Merck. Giugliano reports he has financial ties with Amarin, Amgen, Bristol-Myers Squibb, CVS Caremark, Daiichi Sankyo, GlaxoSmithKline, Lexicon, Merck and Pfizer. Please see the study for the other authors’ relevant financial disclosures.