Baseline Low-Density Lipoprotein Cholesterol and Clinical Outcomes of Combining Ezetimibe With Statin Therapy in IMPROVE-IT

• Published in: Journal of the American College of Cardiology Vol. 78; no. 15; pp. 1499 - 1507
• Main Authors: Oyama, Kazuma, Giugliano, Robert P., Blazing, Michael A., Park, Jeong-Gun, Tershakovec, Andrew M., Sabatine, Marc S., Cannon, Christopher P., Braunwald, Eugene
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.10.2021
• Subjects: acute coronary syndrome; Acute Coronary Syndrome - drug therapy; Aged; Angina, Unstable - epidemiology; Anticholesteremic Agents - therapeutic use; Cardiovascular; Cholesterol, LDL - blood; Double-Blind Method; ezetimibe; Ezetimibe - therapeutic use; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; low-density lipoprotein cholesterol; Male; Middle Aged; Myocardial Infarction - epidemiology; Myocardial Revascularization; Simvastatin - therapeutic use; statin; ACS; acute coronary syndrome; statin; ezetimibe; ASCVD; LDL-C; low-density lipoprotein cholesterol; MI; CTTC; myocardial infarction; atherosclerotic cardiovascular disease; Cholesterol Treatment Trialists Collaboration
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2021.08.011

The 2018 U.S. cholesterol management guideline recommends additional lipid-lowering therapy with ezetimibe for secondary prevention in very high-risk patients with low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL despite maximally tolerated statin. The purpose of this study was to evaluate the relationship between baseline LDL-C above and below 70 mg/dL and the benefit of adding ezetimibe to statin in patients post–acute coronary syndrome (ACS). IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) was a double-blind, placebo-controlled, randomized trial of ezetimibe/simvastatin vs placebo/simvastatin in post-ACS patients followed for 6 years (median). A total of 17,999 patients were stratified by LDL-C at qualifying event into 3 groups (50-<70, 70-<100, and 100-125 mg/dL). The primary endpoint was a composite of cardiovascular death, major coronary events, or stroke. Absolute differences in median LDL-C achieved at 4 months between treatment arms were similar (17-20 mg/dL). The effect of ezetimibe/simvastatin vs placebo/simvastatin on primary endpoint was consistent regardless of baseline LDL-C of 50-<70 mg/dL (HR: 0.92 [95% CI: 0.80-1.05]), 70-<100 mg/dL (HR: 0.93 [95% CI: 0.87-1.01]), or 100-125 mg/dL (HR: 0.94 [95% CI: 0.86-1.03]; P interaction = 0.95). Normalized relative risk reductions per 1-mmol/L difference in achieved LDL-C at 4 months between treatment arms were 21% in patients with baseline LDL-C of 50-<70 mg/dL, 16% in those with 70-<100 mg/dL, and 13% in those with 100-125 mg/dL (P interaction = 0.91). No significant treatment interactions by baseline LDL-C were present for safety endpoints. Adding ezetimibe to statin consistently reduced the risk for cardiovascular events in post-ACS patients irrespective of baseline LDL-C values, supporting the use of intensive lipid-lowering therapy with ezetimibe even in patients with baseline LDL-C <70 mg/dL. (IMPROVE-IT: Examining Outcomes in Subjects With Acute Coronary Syndrome: Vytorin [Ezetimibe/Simvastatin] vs Simvastatin [P04103]; NCT00202878) [Display omitted]