Bempedoic acid lowers MACE risk regardless of sex

Bempedoic acid had a similar efficacy and safety in female and male statin-intolerant patients with or at high risk for CVD compared with placebo, as shown by a prespecified subgroup analysis of CLEAR Outcomes.

This summary is based on the publication of Cho L, Plutzky J, Brennan D, et al. - Impact of Bempedoic Acid on Cardiovascular Outcomes by Sex. Circulation. 2024 Apr 6 [Online ahead of print]. doi: 10.1161/CIRCULATIONAHA.123.067691

Introduction and methods

Background

In the recent CLEAR (Cholesterol Lowering via Bempedoic Acid [ECT1002], an ACL-Inhibiting Regimen) Outcomes trial, bempedoic acid lowered the risk of MACE in patients with or at high risk for CVD who were unable or unwilling to take guideline-recommended doses of statins [1]. Interestingly, this trial enrolled a high percentage of females (48%), making it possible to assess the impact of sex on the treatment effect of bempedoic acid.

Aim of the study

In a prespecified subgroup analysis of the CLEAR Outcomes trial, the authors investigated whether the effect of bempedoic acid on MACE risk varied by sex.

Methods

The CLEAR Outcomes trial was an international, multicenter, double-blind, placebo-controlled, event-driven, phase 3 RCT in which 13,970 statin-intolerant patients with or at high risk for CVD were randomized to oral bempedoic acid 180 mg once daily or placebo. Of the total study population, 6740 were females. Median follow-up duration was 40.6 months.

Outcomes

The primary efficacy endpoint was a 4-component composite outcome of MACE, defined as the time to CV death, nonfatal MI, nonfatal stroke, or coronary revascularization. The key secondary endpoint was a 3-component composite MACE outcome, defined as the time to CV death, nonfatal MI, or nonfatal stroke. Safety analysis included frequencies of adverse events (such as discontinuation of the study drug due to myalgias, liver enzyme elevations, gout, and cholelithiasis) and serious adverse events and changes in uric acid and serum creatinine from baseline to 6 months.

Main results

Efficacy

• In males, bempedoic acid reduced the incidence of the primary endpoint (4-component MACE) compared with placebo (14.8% vs. 16.6%%; adjusted HR: 0.86; 95%CI: 0.77–0.97).
• In females, the incidence of the primary endpoint was 8.4% in the bempedoic acid group and 9.7% in de placebo group (adjusted HR: 0.89; 95%CI: 0.75–1.04; P for interaction=0.82).
• The incidence of the key secondary endpoint (3-component MACE) with bempedoic acid versus placebo was 10.2% versus 11.6% in males (adjusted HR: 0.84; 95%CI: 0.73–0.97) and 6.1% versus 7.2% in females (adjusted HR: 0.88; 95%CI: 0.73–1.06; P for interaction=0.84).

Safety

• The overall safety profile of bempedoic acid was comparable in females and males.

Conclusion

In this prespecified subgroup analysis of the CLEAR Outcomes trial, bempedoic acid reduced the incidence of MACE in statin-intolerant patients with or at high risk for CVD irrespective of sex. There was also no difference in the rate of adverse events between females and males. The authors do point out that, similar to “other cardiovascular trials, specifically cholesterol-lowering trials, the overall cardiovascular event rates in both study arms were lower for females compared to males.”

Find this article online at Circulation.

Reference

1. Nissen SE, Lincoff AM, Brennan D, Ray KK, Mason D, Kastelein JJP, Thompson PD, Libby P, Cho L, Plutzky J, et al. Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients. N Engl J Med. 2023;388:1353–1364.