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

Abstract

BACKGROUND:

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.

OBJECTIVES:

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).

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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).

• Authors: Kazuma Oyama, Robert P Giugliano, Michael A Blazing, Jeong-Gun Park, Andrew M Tershakovec, Marc S Sabatine, Christopher P Cannon, Eugene Braunwald
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 78 Issue 15 Pg. 1499-1507 (10 12 2021) ISSN: 1558-3597 [Electronic] United States
• PMID: 34620406 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Anticholesteremic Agents
• Cholesterol, LDL
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Simvastatin
• Ezetimibe

Topics

• Acute Coronary Syndrome (drug therapy)
• Aged
• Angina, Unstable (epidemiology)
• Anticholesteremic Agents (therapeutic use)
• Cholesterol, LDL (blood)
• Double-Blind Method
• Ezetimibe (therapeutic use)
• Female
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
• Male
• Middle Aged
• Myocardial Infarction (epidemiology)
• Myocardial Revascularization
• Simvastatin (therapeutic use)