CLEAR Outcomes: Bempedoic acid reduces MACE and MALE in patients with PAD

Results of the CLEAR Outcomes trial showed that bempedoic acid was effective in reducing the risk of major adverse limb events (MALE) or major adverse cardiovascular events (MACE) in patients with symptomatic peripheral artery disease (PAD) and an increased risk of cardiovascular disease.

Approximately two-thirds of patients with PAD need combination therapies to reach LDL-cholesterol goals, and many fail to achieve a level <70 mg/dL [1,2]. The CLEAR Outcomes trial included 1,624 statin-intolerant participants with symptomatic PAD who were at increased risk of cardiovascular disease and 12,346 participants without PAD but at increased risk of cardiovascular disease [3]. The participants were randomised 1:1 to bempedoic acid, 180 mg daily, or to placebo. Only about one-third of the 1,624 patients with PAD had polyvascular disease. The study, presented by Prof. Marc Bonaca (University of Colorado, CO, USA), aimed to describe the risk of MALE in patients with PAD and to assess the study drug’s effect on MALE and MACE.

After approximately 40 months of follow-up, the cumulative incidence of MALE in the subgroup of participants with PAD was 8.3% for those on placebo and 5.8% for those on bempedoic acid, reflecting a relative risk reduction of 36% and an absolute risk reduction of 2.5% (HR 0.64; 95% CI 0.44–0.93; P=0.018; see Figure). Furthermore, in participants with PAD, bempedoic acid had a significant effect on total MALE rate (HR 0.55; 95% CI 0.35–0.85; P=0.007), with a lesser absolute effect on those without PAD (HR 0.90; 95% CI 0.64–1.26; P=0.53), and with no significant interaction effect. The authors noted that the incidence of MALE among participants without diagnosed PAD at baseline was 0.5/100 patient-years, indicating that PAD is underdiagnosed in patients at risk for cardiovascular disease. Finally, looking at total MALE or MACE in patients with PAD, the authors documented event rates of 10.5% for participants on placebo and 8.6% for patients on bempedoic acid (RR 0.71; 95% CI 0.54–0.95).

Figure: Risk of MALE in patients with PAD [3]



HR, hazard ratio; MALE, major adverse limb events; PAD, peripheral artery disease.

“LDL-cholesterol lowering should be a top priority in patients with PAD as a safe and effective means of reducing the risk of MALE and MACE,” concluded Prof. Bonaca. Bempedoic acid is an effective agent that should be considered as an option for combination therapy, which is probably needed in most patients to achieve their LDL-cholesterol goals.

1. 
   
   1. Hess CN, et al. J Am Coll Cardiol. 2021;77(24):3016-3027.
   2. Hess CN, et al. J Am Coll Cardiol. 2024;83(25):2658-2670.
   3. Bonaca M, et al. Bempedoic acid and limb outcomes in statin-intolerant patients with peripheral artery disease: new insights from the CLEAR OUTCOMES trial. FS.04, AHA Scientific Sessions 2024, 16–18 November, Chicago, USA.

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Posted on 3 February 2025