Effects of HDL-modifiers on cardiovascular outcomes: A meta-analysis of randomized trials

• A total of 69,515 patients from 18 randomized trials treated with niacin of CETP-inhibitors were included in meta-analysis.
• HDL-modifiers did not significantly reduce cardiovascular mortality.
• Niacin but not CETP significantly reduced myocardial infarction and coronary revascularization.
• No relationship was observed between the extent of HDL changes and benefits from HDL-modifiers.
• HDL-modifiers, increased serious adverse events, as new onset of diabetes mellitus and worsening of hypertension with CETP inhibitors.

Background and aimHigh density lipoproteins (HDL) have been addressed as a potential strategy for cardiovascular prevention, with great controversies on pharmacological approaches for HDL-elevation.Our aim was to compare HDL-rising treatment with niacin or CETP-inhibitors with optimal medical therapy in cardiovascular outcome.Methods and resultsRandomized trials were searched. Primary endpoint was cardiovascular death, secondary were: non fatal myocardial infarction; coronary revascularization; cerebrovascular accidents and safety endpoints.As many as 18 randomized trials, for a total of 69,515 patients, were included. HDL-modifiers did not reduce cardiovascular mortality (2.3%vs3.4%; OR [95%CI] = 0.96 [0.87–1.05], p = 0.37, phet = 0.58), with no benefit from niacin/CETP inhibitors according to patients' risk profile (beta [95%CI] = −0.14 [−0.29 to 0.02], p = 0.09) or the amount of HDL increase (beta [95%CI] = 0.014 [−0.008 to 0.04], p = 0.21). Niacin but not CETP-I reduced myocardial infarction and coronary revascularization, but higher rate of SAE occurred with HDL-modifiers (OR [95%CI] = 1.24 [1.18–1.31], p < 0.00001, phet = 0.02), in particular new onset of diabetes with niacin and worsening of hypertension with CETP-inhibitors.ConclusionsNiacin and CETP inhibitors do not influence cardiovascular mortality. Significant benefits in MI and coronary revascularization were observed with niacin, despite the higher occurrence of diabetes.