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

Background and aim: High 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 results: Randomized 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. Conclusions: Niacin 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.