Clinical Benefit of Bempedoic Acid in Randomized Clinical Trials.

Bempedoic acid is a selective inhibitor of the adenosine triphosphate citrate lyase that reduces low-density lipoprotein cholesterol (LDLc) levels by 17% to 28%. Although the Evaluation of Major Cardiovascular Events in Patients With, or at High Risk for, Cardiovascular Disease Who Are Statin Intolerant Treated With Bempedoic Acid (CLEAR-OUTCOMES) trials demonstrated the efficacy on cardiovascular outcomes there is a controversy related to the possible net clinical benefit. Thereafter, we performed an intention-to-treat meta-analysis in line with recommendations from the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome of the metanalysis was the incidence of major adverse cardiovascular events, defined by each study protocol. Secondary outcomes for the analyses were myocardial infarction, stroke, myocardial revascularization, cardiovascular death, and all-cause death. Results of 4 clinical trials evaluated contained a total of 17,324 patients; 9,236 received bempedoic acid for a median of 46.6 months. The mean baseline LDLc was 129.4 (22.8) mg/100 ml and treatment was associated with a mean LDLc reduction of 26.0 (12.6) mg/100 ml. Treatment with bempedoic acid significantly reduced the incidence of major adverse cardiovascular events (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.81 to 0.96), myocardial infarction (HR 0.76, 95% CI 0.66 to 0.89) and myocardial revascularization (HR 0.82, 95% CI 0.73 to 0.92); the crude incidence of stroke, cardiovascular or all-cause mortality were lower in patients in the bempedoic acid groups although no significant risk reduction was observed. No heterogeneity was observed in any of the end points. In conclusion, the metanalysis of the 4 clinical trials currently available with bempedoic acid provides reliable evidence of its clinical benefit with no signs of heterogeneity or harm.
Competing Interests: Declaration of Competing Interest Dr. Cordero reports honoraria for lectures from AstraZeneca, AMGEN, Bristol-Myers Squibb, Ferrer, Boehringer Ingelheim, Merck Sharp & Dohme, Daiichy Sankio, Novartis, Novo Nordisk, Sanofi and Amarin; and consulting fees from AstraZeneca, Ferrer, Sanofi, AMGEN, Novartis, Lilly, Novo Nordisk and Amarin. Dr. Fernández reports honoraria for lectures from AstraZeneca, AMGEN, Ferrer, Merck Sharp & Dohme, Daiichi Sankio, Novartis, Novo Nordisk, Sanofi, and Amarin; and consulting fees from AstraZeneca, Sanofi, AMGEN, Novartis, Novo Nordisk, and Amarin. Dr. Castellano reports honoraria from Ferrer, Servier, Daiichi Sankyo, and Pfizer. Dr. Fácila reports honoraria for lectures from Eli Lilly Co, Daiichi Sankyo, Inc., Bayer, Pfizer, Novartis Boehringer Ingelheim, and consulting fees from AstraZeneca, Boehringer, Bayer. Dr. Rodriguez-Mañero reports research grants from Fundación Mutua Madrileña, Biosense Webster, Medtronic, and the Carlos III Institute of Health, Ministry of Economy and Competitiveness (Spain). Dr. Bonanad has received fees from AstraZeneca; Amgen, Bayer; Boehringer; Bristol-Myers Squibb; Daiichi Sankyo; Ferrer; Novartis AG; Pfizer; Roche Pharma; Sanofi Pharma. Dr. González Juanatey reports honoraria for lectures from Eli Lilly Co, Daiichi Sankyo, Inc., Bayer, Pfizer, Abbott, Boehringer Ingelheim, Merck Sharp & Dohme, Ferrer, and Bristol-Myers Squibb; consulting fees from AstraZeneca, Ferrer, Bayer, Boehringer Ingelheim; and research grants from AstraZeneca, Boehringer Ingelheim and Daichi-Sankyo. The remaining authors have no competing interests to declare.
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