A nonstatin, ezetimibe, inhibits absorption of cholesterol, reduces LDL-C and thereby reduces cardiovascular events after acute coronary syndrome (ACS), when used as an adjunct to statins. In the IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) Giugliano et al. explored outcomes in 18144 ACS patients randomized to receive ezetimibe/simvastatin (E/S) or placebo/simvastatin. In a pre-specified subgroup of 4933 patients with diabetes mellitus (DM), the authors reported the same beneficial trend of reduced cardiovascular events. In this subgroup, the primary end point event rate (defined as cardiovascular death, major coronary events and stroke) was decreased by 5.5% absolute; in patients without DM, the absolute difference was 0.7%. No differences in safety outcomes by treatment were present. DM patients showed greatest relative reductions in myocardial infarction and ischemic stroke.
Further dichotimization by age showed patients < 75 years of age with DM demonstrated greater benefit than those without. Meanwhile, patients >75 years of age displayed a greater benefit (20% relative reduction in the primary endpoint), regardless of DM.
Giugliano et al. conclude that for patients with an ACS, physicians should consider combining ezetimibe with statins to reduce cardiovascular risk.
In letters from colleagues, Donzelli et al. point out that in patients younger than 75 years of age without DM, endpoints were in fact worse in the E/S group, and that there is little evidence for statin therapy in patients over the age of 75; Koh observes that patients with a low to moderate risk profile demonstrated no added benefit from the addition of ezetimibe to simvastatin, and remarks upon the increased risk of DM with statin use.
Original article: Circulation. 2018 Apr 10;137(15):1571-1582.
Letters: Circulation. 2018 Oct 23;138(17):1912-1913.
Circulation. 2018 Oct 23;138(17):1914-1915.
Author: Kelly Schoonderwoerd
