June 25, 2025

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Ezetimibe With Statin Therapy Reduces Risk Of CV Events Even In Patients With Low LDL-C: Study

USA: According to a recent study in the Journal of the American College of Cardiology (JACC), ezetimibe addition to statin consistently reduces the risk for cardiovascular (CV) events in post-acute coronary syndrome (ACS) patients. The risk reduction was irrespective of baseline LDL-C values, implying the use of intensive lipid-lowering therapy with ezetimibe even in patients with baseline LDL-C <70 mg/dL.
Additional lipid-lowering therapy with ezetimibe is recommended in the 2018 U.S. cholesterol management guideline for secondary prevention in very high-risk patients with low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL despite maximally tolerated statin.
To fill this knowledge gap, Kazuma Oyama, Harvard Medical School, Boston, Massachusetts, USA, and colleagues aimed to evaluate the relationship between baseline LDL-C above and below 70 mg/dL and the benefit of adding ezetimibe to a statin in patients post-acute coronary syndrome (ACS).
IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) is 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.
The study yielded the following findings:
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), 70-<100 mg/dL (HR: 0.93), or 100-125 mg/dL (HR: 0.94).
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.
No significant treatment interactions by baseline LDL-C were present for safety endpoints.
The researchers concluded that adding ezetimibe to statin consistently reduced the risk for CV 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.
Reference:
The study titled, "Baseline Low-Density Lipoprotein Cholesterol and Clinical Outcomes of Combining Ezetimibe With Statin Therapy in IMPROVE-IT," is published in the Journal of the American College of Cardiology (JACC).
DOI: https://www.jacc.org/doi/10.1016/j.jacc.2021.08.011

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