Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients
Abstract
Importance: The effects of bempedoic acid on cardiovascular outcomes in statin-intolerant patients without a prior cardiovascular event (primary prevention) have not been fully described.
Objective: To determine the effects of bempedoic acid on cardiovascular outcomes in primary prevention patients.
Design, setting, and participants: This masked, randomized clinical trial enrolled 13 970 statin-intolerant patients (enrollment December 2016 to August 2019 at 1250 centers in 32 countries), including 4206 primary prevention patients.
Interventions: Participants were randomized to oral bempedoic acid, 180 mg daily (n = 2100), or matching placebo (n = 2106).
Main outcome measures: The primary efficacy measure was the time from randomization to the first occurrence of any component of a composite of cardiovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, or coronary revascularization.
Results: Mean participant age was 68 years, 59% were female, and 66% had diabetes. From a mean baseline of 142.2 mg/dL, compared with placebo, bempedoic acid reduced low-density lipoprotein cholesterol levels by 30.2 mg/dL (21.3%) and high-sensitivity C-reactive protein levels by 0.56 mg/L (21.5%), from a median baseline of 2.4 mg/L. Follow-up for a median of 39.9 months was associated with a significant risk reduction for the primary end point (111 events [5.3%] vs 161 events [7.6%]; adjusted hazard ratio [HR], 0.70 [95% CI, 0.55-0.89]; P = .002) and key secondary end points, including the composite of cardiovascular death, MI, or stroke (83 events [4.0%] vs 134 events [6.4%]; HR, 0.64 [95% CI, 0.48-0.84]; P < .001); MI (29 events [1.4%] vs 47 events [2.2%]; HR, 0.61 [95% CI, 0.39-0.98]); cardiovascular death (37 events [1.8%] vs 65 events [3.1%]; HR, 0.61 [95% CI, 0.41-0.92]); and all-cause mortality (75 events [3.6%] vs 109 events [5.2%]; HR, 0.73 [95% CI, 0.54-0.98]). There was no significant effect on stroke or coronary revascularization. Adverse effects with bempedoic acid included a higher incidence of gout (2.6% vs 2.0%), cholelithiasis (2.5% vs 1.1%), and increases in serum creatinine, uric acid, and hepatic enzyme levels.
Conclusions: In a subgroup of high-risk primary prevention patients, bempedoic acid treatment was associated with reduced major cardiovascular events.
RPR Commentary
In this large RCT of patients at very high risk of CV events but no history of events, bempedoic acid 180mg daily reduced risk of MI, cardiovascular mortality, and all-cause mortality by 0.8%, 1.3%, and 1.6% (absolute risk reductions) respectively over a period of 39 months.