The class
Meta-analysis finds adding a CETP inhibitor to statin therapy does not reduce cardiovascular events (Int J Cardiol 2015)
Original title: Effects of add-on lipid-modifying therapy on top of background statin treatment on major cardiovascular events: A meta-analysis of randomized controlled trials
In a meta-analysis of eleven randomised controlled trials with 109,244 high-risk patients, researchers tested whether adding lipid-modifying agents to statin therapy improves cardiovascular outcomes beyond statins alone. Overall, major adverse cardiovascular events occurred in 9.70 percent of combination-therapy patients versus 9.92 percent of statin-monotherapy patients, a non-significant difference (relative risk 0.99). In subgroup analysis, adding a CETP inhibitor to statins showed no significant benefit (relative risk 1.07, 95 percent CI 0.93 to 1.23, P = 0.37), similar to niacin, omega-3 fatty acid, and fenofibrate add-on therapy, while only statin-ezetimibe combination significantly reduced events (relative risk 0.92, P = 0.004). Adding lipid-modifying agents to statins also increased liver injury risk, except for ezetimibe.
Original abstract
Background: In patients at high risk of atherosclerotic cardiovascular diseases (ASCVDs), residual cardiovascular risk persists despite the achievement of target LDL cholesterol levels with statin therapy. It is still unclear whether adding lipid-modifying agent to statin treatment can further improve clinical outcomes.
Methods: Randomized controlled trials (RCTs) in terms of adding lipid-modifying agent to statin versus statin monotherapy in patients at high risk of ASCVD were identified by electronic and manual searches. Results were expressed as relative risk (RR) with 95% confidence intervals (CIs).
Results: Eleven RCTs with 109,244 patients were included in this meta-analysis. Overall, the incidences of major adverse cardiovascular events (MACEs) were 9.70% in the statin combination groups and 9.92% in the statin monotherapy groups. No significant difference was observed in the risk of MACEs either in overall (RR 0.99, 95% CI 0.93-1.05, P=0.76) or subgroup analysis (CETP inhibitor: RR 1.07, 95% CI 0.93-1.23, P=0.37; niacin: RR 1.03, 95% CI 0.85-1.25, P=0.79; n-3 fatty acid: RR 0.98, 95% CI 0.88-1.09, P=0.70; fenofibrate: RR 0.93, 95% CI 0.80-1.09, P=0.38), with the exception of the statin/ezetimibe combination subgroup (RR 0.92, 95% CI 0.87-0.97, P=0.004). Adding lipid-modifying agent to statin significantly increased liver injury risk. Adding ezetimibe to statin did not alter side effect profile.
Conclusion: Adding niacin, CETP inhibitors, n-3 fatty acid or fibrates to statin therapy has all failed to achieve a clinical benefit. Adding ezetimibe to statin therapy further lowers LDL-cholesterol safely and translates into a clinical benefit in patients at high risk of ASCVD.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.