Cholesteryl Ester Transfer Protein Inhibitors and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Background: Cholesteryl ester transfer protein (CETP) inhibitors increase serum high-density lipoprotein cholesterol (HDL-c) concentration; however, their impact on cardiovascular outcomes is not clear. This systematic review examines the effect of CETP inhibitors on serum lipid profiles, cardiovascular events, and all-cause mortality. Methods: We searched MEDLINE, Embase, and the Cochrane Library of Clinical Trials for placebo-controlled randomized controlled trials (RCTs) that examined the effect of a CETP inhibitor (dalcetrapib, anacetrapib, evacetrapib, or TA-8995) on all-cause mortality, major adverse cardiovascular events (MACE), or the components of MACE at ≥6 months. Data were pooled using random-effects models. Results: A total of 11 RCTs (n = 62,431) were included in our systematic review; 4 examined dalcetrapib (n = 16,612), 6 anacetrapib (n = 33,682), and 1 evacetrapib (n = 12,092). Compared to dalcetrapib, ana­cetrapib and evacetrapib were more efficacious at raising HDL-c levels (∼100–130 vs. ∼30%). Anacetrapib and evacetrapib also decreased low-density lipoprotein cholesterol (LDL-c) by approximately 30% while dalcetrapib did not affect the LDL-c level. Overall, CETP inhibitors were not associated with the incidence of MACE (pooled relative risk [RR]: 0.97; 95% confidence interval [CI]: 0.91–1.04). CETP inhibitors may decrease the risks of nonfatal myocardial infarction (MI) (RR: 0.93; 95% CI: 0.87–1.00) and cardiovascular death (RR: 0.92; 95% CI: 0.83–1.01), though these trends did not reach statistical significance. Conclusions: CETP inhibitors are not associated with an increased risk of MACE or all-cause mortality. There is a trend towards small reductions in nonfatal MI and cardiovascular death, though the clinical im­portance of such reductions is likely modest.