Adding Ezetimibe to Statin Therapy: Cardiovascular Outcomes in Diabetes
The benefits of ezetimibe were achieved without an increase in safety events compared to placebo.
Adding ezetimibe to statin therapy may help reduce cardiovascular events in patients with diabetes and in high-risk patients without diabetes, according to a study published in Circulation.1
In IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial; ClinicalTrials.gov identifier: NCT00202878), investigators randomly assigned 18,144 patients with recent acute coronary syndrome and a low-density lipoprotein cholesterol of 50 to 125 mg/dL to receive either ezetimibe/simvastatin-40 mg (E/S) or placebo/simvastatin-40 mg (P/S).1 Of these patients, 4933 had diabetes (27.4%; E/S group, n=2459; P/S group, n=2474) and 13,202 did not have diabetes (72.6%; E/S group, n=6604; P/S group, n=6598).
Researchers found that patients with diabetes derived significantly greater relative and absolute benefit from the addition of ezetimibe to simvastatin therapy compared with patients who received placebo in addition to simvastatin therapy relative to patients without diabetes.
The largest relative reductions were observed in acute ischemic events, such as myocardial infarction (24%) and ischemic stroke (39%) in patients with diabetes. Among patients without diabetes who were at high risk for cardiovascular events either because of older age (>75 years) or an elevated risk score, significant reductions in cardiovascular events were observed in patients who received ezetimibe compared with those who received placebo.
No added benefit was observed in patients without diabetes who were less than 75 years of age or who had a low risk score. In addition, no differences in the safety profiles of treatments were observed regardless of diabetes status.
This is the only large cardiovascular outcomes study that compared treatment with ezetimibe with placebo in addition to simvastatin therapy.1 The investigators concluded that, “These findings support the use of intensive, combination lipid lowering therapy in patients with [diabetes] to optimize cardiovascular outcomes, as recommended by the American Association of Clinical Endocrinologists and American College of Endocrinology.”1,2
- Giugliano RP, Cannon CP, Blazing MA, et al; IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) Investigators. Benefit of adding ezetimibe to statin therapy on cardiovascular outcomes and safety in patients with vs. without diabetes: results from IMPROVE-IT [published online December 20, 2017]. Circulation. doi: 10.1161/CIRCULATIONAHA.117.030950
- Jellinger PS, Handelsman Y, Rosenblit PD, et al. American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease. Endocr Pract. 2017;23:1-87.