European Primary Care Cardiovascular Society

Bempedoic acid use results in long-term and safe LDL-c reduction

Long-Term Safety and Efficacy of Bempedoic Acid in Patients With Atherosclerotic Cardiovascular Disease and/or Heterozygous Familial Hypercholesterolemia (from the CLEAR Harmony Open-Label Extension Study)

Literature - Ballantyne CM, Banach M, Bays HE, et al. - Am J Cardiol. 2022;S0002-9149(22)00322-8. doi: 10.1016/j.amjcard.2022.03.020

Introduction and methods

Background

In patients with ASCVD and/or heterozygous familial hypercholesterolemia (HeFH), long-term reduction of LDL-c levels is recommended [1,2]. Despite statin or other lipid-lowering therapy, many patients at high CVD risk are unable to achieve risk-based LDL-c–lowering goals [3,4]. To help them reach these goals while minimizing side effects, there is a need for nonstatin treatments.

Aim of the study

The authors set out to investigate the long-term safety and efficacy of the prodrug bempedoic acid, an oral ATP -citrate lyase inhibitor that lowers LDL-c levels in patients with hypercholesterolemia.

Methods

This 78-week open-label extension (OLE) study was a follow-up study of the CLEAR (Cholesterol Lowering via Bempedoic acid, an ACL-Inhibiting Regimen) Harmony trial [5]. In this previous multicenter, double-blind, placebo-controlled, parallel-group, phase 3 RCT, patients with ASCVD and/or HeFH had been randomized (2:1) to receive bempedoic acid 180 mg or placebo once daily for 52 weeks. At the time, inclusion criteria were baseline LDL-c level ≥70 mg/dL and maximally tolerated background statin therapy with or without additional lipid-lowering therapy.

In the OLE study, 970 patients who had been assigned to the experimental arm continued treatment for 78 weeks (total duration of bempedoic acid therapy: ≤ 130 weeks), while bempedoic acid treatment was initiated in 492 patients in the control arm (≤ 78 weeks of bempedoic acid therapy). All patients enrolled in the OLE study received ≥1 bempedoic acid dose. At baseline, patient demographics and characteristics were generally similar regardless of whether patients had received bempedoic acid or placebo in the parent study (i.e., CLEAR Harmony trial).

Outcomes

The primary endpoint was safety, as assessed by the incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, and adverse events of special interest (AESIs). The secondary endpoint was efficacy, as assessed by absolute and relative changes from baseline of the parent study to week 52 and to week 78 of the OLE study (total of 130 weeks) in levels of LDL-c, total cholesterol (TC), non–HDL-c, HDL-c, triglycerides, apoB , and high-sensitivity CRP (hsCRP).

Main results

Safety

Efficacy

Drug discontinuation

Conclusion

Bempedoic acid as an adjunct to maximally tolerated statins was generally well tolerated and showed sustained efficacy in lowering LDL-c levels with up to 2.5 years of continuous treatment in patients with ASCVD and/or HeFH. Safety profiles were similar between the parent and OLE studies, and no new safety signals were identified.

References

Show references

Find this article online at Am J Cardiol.

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