Ezetimibe Plus Statins Modestly Reduce Cardiovascular Disease Event Risk

Chest angiogram, MRI
Chest angiogram, MRI
Ezetimibe combined with statin therapy showed modest or moderate benefits in reducing major CVD event risk.

Ezetimibe combined with statin therapy showed modest or moderate benefits in reducing major cardiovascular disease (CVD) event risk and CVD-associated mortality, according to a recent study published in the Cochrane Database of Systematic Reviews.

Researchers conducted a systematic literature review and meta-analyses to assess the efficacy and safety of ezetimibe for CVD and all-cause mortality prevention. Reports of randomized controlled trials (RCTs) with at least 12-month follow-up and adult participants of at least 18 years of age, with or without established CVD, were included in the review.

Cluster-RCTs, cross-over trials, and nonrandomized studies were excluded from the analysis. RCTs were included in the analysis if their interventions compared 1) ezetimibe vs placebo, and 2) ezetimibe plus other lipid-modifying drug(s) vs other lipid-modifying drug(s) alone or in addition to placebo.

Primary outcomes measured were major adverse cardiovascular events and all-cause mortality. Secondary outcomes were myocardial infarction, fatal and nonfatal ischemic stroke, cardiovascular mortality, lipid parameters, adverse events, coronary revascularization, and health-related quality of life.

Dichotomous data were examined as risk ratios with 95% confidence intervals. Subgroup analyses were performed based on two factors: 1) duration of follow-up and 2) participants with or without existing atherosclerotic CVD.

Study investigators’ literature search returned 7180 records. After screening for inclusion and exclusion criteria, as well as removing duplicates, 26 studies with 108 records (including 23,499 randomized participants) remained for qualitative synthesis, and 21 remained for quantitative synthesis (meta-analysis). Risk of bias was ascertained for each study selected for inclusion.  

Ezetimibe taken with statins modestly reduced the risk of major adverse cardiovascular events vs statins alone (n = 21,727; relative risk [RR], 0.94; 95% CI, 0.90-0.98). Trials reporting all-cause mortality that used ezetimibe with statin or fenofibrate found similarly modest results (n = 21,222; RR, 0.98; 95% CI, 0.91-1.05).

The findings were largely driven by the largest study included in the analysis (IMPROVE-IT, ClinicalTrials.gov Identifier: NCT00202878), whose weights were between 41.5% to 98.4% among the studies included in the review.

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Limitations listed that more than 90% of the study participants within the included RCTs were diagnosed with atherosclerotic CVD due to acute coronary syndrome. The efficacy of lipid-lowering drugs on CVD outcomes might be decreased in individuals with acute coronary syndrome and influenced by underlying changes in lipid levels that occur 3 to 6 months after treatment commencement.  

The researchers described their review as comprehensive because they included a large number RCTs in their analysis, assessed a large number of outcomes using unpublished data submitted to regulatory bodies, such as the Food and Drug Administration, and performed subgroup and sensitivity analyses.

They concluded that ezetimibe monotherapy as a mechanism for CVD prevention remains unknown and thus warrants further investigation.

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Zhan S, Tang M, Liu F, Xia P, Shu M, Wu X. Ezetimibe for the prevention of cardiovascular disease and all-cause mortality eventsCochrane Database Syst Rev. 2018,11:CD012502.

This article originally appeared on The Cardiology Advisor