The class
BMJ meta-analysis of 117,411 patients finds niacin, fibrates, and CETP inhibitors do not reduce mortality on top of statins (BMJ 2014)
Original title: Effect on cardiovascular risk of high density lipoprotein targeted drug treatments niacin, fibrates, and CETP inhibitors: meta-analysis of randomised controlled trials including 117,411 patients
This meta-analysis pooled 39 randomised controlled trials (117,411 patients) testing niacin, fibrates, and cholesteryl ester transfer protein (CETP) inhibitors, all of which raised HDL cholesterol, against cardiovascular outcomes. None of the three drug classes significantly reduced all-cause mortality (CETP inhibitors: odds ratio 1.16, 95% CI, 0.93 to 1.44, P=0.19), coronary heart disease mortality (odds ratio 1.00, 95% CI, 0.80 to 1.24, P=0.99), or stroke (odds ratio 1.14, 95% CI, 0.90 to 1.45, P=0.29). Niacin reduced non-fatal myocardial infarction in pre-statin-era trials (odds ratio 0.69, 95% CI, 0.56 to 0.85, P=0.0004) but not in trials where patients also took statins (odds ratio 0.96, 95% CI, 0.85 to 1.09, P=0.52), a significant subgroup difference (P=0.007), with a similar trend for fibrates. The authors conclude that none of niacin, fibrates, or CETP inhibitors reduced mortality, myocardial infarction, or stroke in statin-treated patients, challenging the simple hypothesis that pharmacologically raising HDL cholesterol reduces cardiovascular events.
Original abstract
Objective: To investigate the effects on cardiovascular outcomes of drug interventions that increase high density lipoprotein levels.
Design: Meta-analysis.
Studies Reviewed: Therapeutic benefit of niacin, fibrates, and cholesteryl ester transfer protein (CETP) inhibitors on cardiovascular events (all cause mortality, coronary heart disease mortality, non-fatal myocardial infarction, and stroke).
Results: 117,411 patients were randomised in a total of 39 trials. All interventions increased the levels of high density lipoprotein cholesterol. No significant effect was seen on all cause mortality for niacin (odds ratio 1.03, 95% confidence interval 0.92 to 1.15, P=0.59), fibrates (0.98, 0.89 to 1.08, P=0.66), or CETP inhibitors (1.16, 0.93 to 1.44, P=0.19); on coronary heart disease mortality for niacin (0.93, 0.76 to 1.12, P=0.44), fibrates (0.92, 0.81 to 1.04, P=0.19), or CETP inhibitors (1.00, 0.80 to 1.24, P=0.99); or on stroke outcomes for niacin (0.96, 0.75 to 1.22, P=0.72), fibrates (1.01, 0.90 to 1.13, P=0.84), or CETP inhibitors (1.14, 0.90 to 1.45, P=0.29). In studies with patients not receiving statins (before the statin era), niacin was associated with a significant reduction in non-fatal myocardial infarction (0.69, 0.56 to 0.85, P=0.0004). However, in studies where statins were already being taken, niacin showed no significant effect (0.96, 0.85 to 1.09, P=0.52). A significant difference was seen between these subgroups (P=0.007). A similar trend relating to non-fatal myocardial infarction was seen with fibrates: without statin treatment (0.78, 0.71 to 0.86, P<0.001) and with all or some patients taking statins (0.83, 0.69 to 1.01, P=0.07); P=0.58 for difference.
Conclusions: Neither niacin, fibrates, nor CETP inhibitors, three highly effective agents for increasing high density lipoprotein levels, reduced all cause mortality, coronary heart disease mortality, myocardial infarction, or stroke in patients treated with statins. Although observational studies might suggest a simplistic hypothesis for high density lipoprotein cholesterol, that increasing the levels pharmacologically would generally reduce cardiovascular events, in the current era of widespread use of statins in dyslipidaemia, substantial trials of these three agents do not support this concept.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.