Background: Bempedoic acid (BA) is a novel oral low-density lipoprotein cholestrol (LDL-C) lowering drug. Its efficacy and safety for clinical outcomes in high cardiovascular risk patients remains unknown.

Methods: A systematic review was performed and randomized controlled trials (RCTs) of BA vs. placebo in high cardiovascular risk patients reporting clinical efficacy and safety outcomes were included in a meta-analysis. Cumulative odds ratios (OR) and mean differences with 95% confidence intervals (CI) were reported as summary statistics.

Results: Six RCTs with a total of 4,065 patients and follow-ups of four to 52 weeks were identified. There was no difference in MACE (OR 0.84; CI 0.61 to 1.15), all-cause mortality (OR 2.37; CI 0.80 to 6.99) and cardiovascular mortality (OR 1.66; CI 0.45 to 6.04) for BA vs. placebo, but a borderline difference in non-fatal myocardial infarction (OR 0.57; CI 0.32 to 0,99; p = 0.05). BA was associated with a significantly lower risk of new-onset or worsening of diabetes mellitus (OR 0.68; CI 0.49 to 0.94) and non-coronary revascularization (OR 0.41; CI 0.18 to 0.95), but higher risk of gout (OR 3.29; CI 1.28 to 8.46) and a trend for worsening of renal function (OR 4.24; CI 0.98 to 18.39) and muscular disorders (OR 2.60; CI 1.15 to 5.91). LDL-C levels (mean difference -20%; p<0.01) and total cholesterol (mean difference -12%; p<0.01) were significantly reduced.

Conclusion: Bempedoic acid in high cardiovascular risk patients showed no significant effects on major cardiovascular outcomes in studies with short-term follow-up. Unfavourable effects on muscular disorders, renal function and the incidence of gout sound a note of caution. Further studies with longer-term follow-up are needed to clarify the risk/benefit ratio of this novel therapy.