The class
Meta-regression of 167 311 patients finds raising HDL cholesterol with CETP inhibitors does not predict clinical benefit (Heart 2015)
Original title: Clinical benefit from pharmacological elevation of high-density lipoprotein cholesterol: meta-regression analysis
Researchers performed a meta-regression of 51 secondary-prevention trials totalling 167,311 patients, testing raising HDL-C drugs (statins, fibrates, niacin, and CETP inhibitors) for an association between change in HDL cholesterol and clinical outcomes. Overall, change in HDL-C was not significantly associated with the log risk ratio for non-fatal myocardial infarction or cardiac death, and CETP inhibitor data were consistent with this null finding (relative risk 1.03, P5-P95 0.99 to 1.21). A prespecified sensitivity analysis found a significant HDL-C-outcome relationship for statins and niacin but not fibrates, though these associations weakened after adjusting for LDL cholesterol or excluding open trials. The authors conclude CETP inhibitors likely do not influence coronary risk, and that HDL-C may be a drug-dependent, unreliable surrogate marker of coronary events.
Original abstract
Context: Epidemiological evidence that the risk of coronary heart disease is inversely associated with the level of high-density lipoprotein cholesterol (HDL-C) has motivated several phase III programmes with cholesteryl ester transfer protein (CETP) inhibitors.
Objectives: To assess alternative methods to predict clinical response of CETP inhibitors.
Methods: Meta-regression analysis on raising HDL-C drugs (statins, fibrates, niacin) in randomised controlled trials.
Results: 51 trials in secondary prevention with a total of 167,311 patients for a follow-up >1 year where HDL-C was measured at baseline and during treatment. The meta-regression analysis showed no significant association between change in HDL-C (treatment vs comparator) and log risk ratio (RR) of clinical endpoint (non-fatal myocardial infarction or cardiac death). CETP inhibitors data are consistent with this finding (RR: 1.03; P5-P95: 0.99-1.21). A prespecified sensitivity analysis by drug class suggested that the strength of relationship might differ between pharmacological groups. A significant association for both statins (p<0.02, log RR=-0.169-0.0499*HDL-C change, R(2)=0.21) and niacin (p=0.02, log RR=1.07-0.185*HDL-C change, R(2)=0.61) but not fibrates (p=0.18, log RR=-0.367+0.077*HDL-C change, R(2)=0.40) was shown. However, the association was no longer detectable after adjustment for low-density lipoprotein cholesterol for statins or exclusion of open trials for niacin.
Conclusions: Meta-regression suggested that CETP inhibitors might not influence coronary risk. The relation between change in HDL-C level and clinical endpoint may be drug dependent, which limits the use of HDL-C as a surrogate marker of coronary events. Other markers of HDL function may be more relevant.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.