Stat-Intolerable: Bempedoic Acid a Clear Alternative

The results of the CLEAR (Cholesterol Lowering via Bempedoic Acid, an ACL-inhibiting Regimen) Outcomes trial support bempedoic acid as an evidence-based alternative to statins for primary and secondary prevention of cardiovascular disease.¹

Statins are the cornerstone of treatment and prevention in patients with or at risk for atherosclerotic cardiovascular disease, a progressive condition associated with significant morbidity and mortality from heart attack, stroke, and peripheral arterial disease.² However, a significant portion of patients are unable or unwilling to take statins due for a variety of reasons including primarily muscle symptoms.³ The CLEAR Outcomes trial directly addresses the problem of statin-intolerant patients.

This double-blind, randomized, placebo-controlled study enrolled nearly 14,000 patients at over 1,200 sites in 32 countries. To participate, eligible patients and corresponding site coordinators had to confirm statin-intolerance. Participating patients were then randomized 1:1 to receive either bempedoic acid or a placebo. Enrolled patients were about 65 years old, and notably 48% were women, 17% were Hispanic, and 70% had had a previous cardiovascular event, prompting Dr. Ann Marie Navar, Associate Professor at UT Southwestern Medical Center, to say “[thank you] for pulling off a trial that actually enrolls patients that look like those who we’re treating in clinical practice.”

In terms of efficacy, bempedoic acid outperformed placebo for the primary composite end point of four-component MACE (death from cardiovascular cause, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization) which occurred in 11.7% of patients taking bempedoic acid and 13.3% in patients taking placebo (Hazard Ratio = 0.87, P = 0.004), along with several secondary end points including reduction in LDL and CRP. There was no significant difference in mortality.

In terms of safety, patients taking bempedoic acid did experience a higher rate of adverse events including renal impairment and elevated hepatic enzymes; however, these side effects did not lead to a higher rate of drug discontinuation.

Statin intolerance is a frustrating and hazy ordeal to navigate, both for physicians and patients. “Management of patients unable or unwilling to take statins represents a challenging and frustrating clinical issue,” said Dr. Steven E. Nissen, MD, MACC, chief academic officer of the Heart Vascular and Thoracic Institute at Cleveland Clinic and chair of the study. “Regardless whether this problem represents the nocebo effect or actual intolerance, these high-risk patients need effective alternative therapies.”

The CLEAR Outcomes trial has certainly provided bempedoic acid as a step towards a clearer future for patients with or at risk for ASCVD.

Dr. Kansal is a fellow at Duke University and served as a CardioNerds Conference Scholar for the American College of Cardiology 2023 Scientific Sessions.

References

Nissen SE, Lincoff AM, Brennan D, et al. Bempedoic acid and cardiovascular outcomes in statin-intolerant patients. N Engl J Med. DOI: 10.1056/NEJMoa2215024.

Mihaylova B, Emberson J, Blackwell L, et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet 2012;380:581-590.

Cholesterol Treatment Trialists’ Collaboration. Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials. Lancet 2022;400:832-845.