Abstract 12263: Inflammation and Cholesterol as Predictors of Cardiovascular Events and Risk Reduction With Bempedoic Acid Among Statin Intolerant Patients: An Analysis of the CLEAR Outcomes Trial

Abstract

Introduction: Among contemporary statin-treated patients, residual inflammatory risk assessed by high-sensitivity C-reactive protein (hsCRP) is a stronger predictor of future cardiovascular (CV) events and all-cause mortality than residual cholesterol risk assessed by low density lipoprotein cholesterol (LDLC). Whether these relationships are present among statin-intolerant patients is unknown but has implications for the choice of preventive therapies including bempedoic acid, an agent that reduces both LDLC and hsCRP. Methods: In the multi-national CLEAR-Outcomes trial, 13,970 statin-intolerant patients were randomly allocated 1:1 to 180 mg oral bempedoic acid daily or matching placebo and followed for incident myocardial infarction (MI), stroke, coronary revascularization, CV death, and all-cause mortality. Quartiles of increasing baseline hsCRP and LDLC were assessed as predictors of future adverse CV events after adjustment for traditional risk factors and treatment (bempedoic acid vs. placebo). Results: Baseline hsCRP was significantly associated with incident composite endpoint of MI, stroke, coronary revascularization, and CV death (highest vs lowest hsCRP quartile, HR=1.43, 95% CI 1.24-1.65), CV mortality (HR=2.00, 95% CI 1.53-2.61), and all-cause mortality (HR=2.21, 95% CI 1.79-2.73). By contrast, the relationship of baseline LDLC quartile (highest vs. lowest) to future CV events was smaller for the composite endpoint (HR=1.19, 95% CI 1.04-1.37) and neutral for CV mortality (HR 0.90, 95% CI 0.70-1.17) and all-cause mortality (HR 0.95, 95% CI 0.78-1.16) such that risks were high for those with elevated hsCRP irrespective of LDLC level. Compared to placebo, bempedoic acid reduced median hsCRP by 21.6% and mean LDLC levels by 21.1% at 6 months and demonstrated similar efficacy in reducing major adverse CV events across all levels of hsCRP and LDLC. Interpretation: Among contemporary statin-intolerant patients, inflammation assessed by hsCRP was a stronger predictor of risk for future CV events and death than was hyperlipidemia assessed by LDLC. Compared to placebo, bempedoic acid had similar efficacy for reducing CV risk across hsCRP and LDLC strata.