Effects of high

The effects of increasing high-density lipoprotein cholesterol on cardiovascular outcomes remain uncertain. We conducted a meta-analysis to investigate the effects of high-density lipoprotein cholesterol modifiers (niacin, fibrates and cholesteryl ester transfer protein inhibitors) on cardiovascular outcomes. Thirty-one randomized controlled trials (154,601 patients) with a follow-up of 6 months or more and a sample size of 100 or more patients were selected using MEDLINE, EMBASE and CENTRAL database (inception January 2018). High-density lipoprotein cholesterol modifiers had no statistically significant effect on cardiovascular mortality in terms of relative risk (RR) (RR 0.94, 95% confidence interval (CI) 0.89–1.00, P？=？0.05, I2？=？13%) or absolute risk (risk difference ？0.0001, 95% CI ？0.0014, 0.0011, P？=？0.84, I2？=？28%). High-density lipoprotein cholesterol modifiers reduced the RR of myocardial infarction (RR 0.87, 95% CI 0.82–0.93, P？<？0.001, I2？=？37%). This significant effect was derived by the use of fibrates (RR 0.80, 95% CI 0.73–0.87, P？<？0.001, I2？=？22%) and meta-regression analysis showed that this benefit was consistent with an absolute reduction in low-density lipoprotein cholesterol. High-density lipoprotein cholesterol modifiers had no effect on stroke (RR 1.00, 95% CI 0.93–1.09, P？=？0.94, I2？=？25%) or all-cause mortality (RR 1.02, 95% CI 0.97–1.08, P？=？0.48, I2？=？49%). Meta-regression analyses failed to demonstrate a significant association of pharmacologically increased high-density lipoprotein cholesterol with key endpoints. In studies with background statin therapy, high-density lipoprotein cholesterol modifiers had no statistically significant impact on cardiovascular mortality, myocardial infarction, stroke or all-cause mortality (P？>？0.05). The use of high-density lipoprotein cholesterol modifying treatments had no significant effect on cardiovascular mortality, stroke or all-cause mortality. The beneficial effect on myocardial infarction was lost when drugs were used with statin therapy