Cardiovascular events in patients treated with bempedoic acid vs.placebo: systematic review and meta-analysis

Aims Reduction of low-density lipoprotein cholesterol (LDL- C) decreases cardiovascular mortality and morbidity. Bempedoic acid represents a promising novel lipid-modifying agent for patients who cannot reach guideline recommended LDL- C goals or statin-intolerant patients, but data on safety and cardiovascular outcomes are limited. We therefore aimed to systematically review randomized controlled trials investigating bempedoic acid vs. placebo in patients with hyperlipidaemia. Methods A systematic search on the databases PubMed, Web of Science, and Embase until 20 March 2023 was performed. All randomized trials comparing bempedoic acid (180 mg daily) with placebo in patients with an indication for lipid-lowering therapy were included. As a primary endpoint, we analysed three-point major adverse cardiovascular events (MACEs) consisting of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke. The analysis was carried out using the odds ratio (OR) as the outcome measure. Due to the expected heterogeneity across studies, a random- effects model was fitted to the data. Results Out of 258 manuscripts, 10 manuscripts fulfilled the inclusion criteria. In total, these trials included 18 200 patients (9765 on bempedoic acid, 8435 on placebo). Bempedoic acid significantly reduced MACEs compared with placebo (OR 0.84 [95% confidence interval (CI) 0.76-0.96]; P < 0.001; I-2 = 0%). The endpoint reduction was driven by a lower rate of non-fatal MI, whereas bempedoic acid had no significant effect on stroke (OR 0.86 [95% CI 0.69-1.08]; P = 0.20, I-2 = 0%) and all-cause mortality (OR 1.19 [95% CI 0.73-1.93]; P = 0.49; I-2 = 18%) Conclusion Bempedoic acid reduced non-fatal MI in patients with hyperlipidaemia, whereas it had no significant effect on stroke and all-cause mortality.