Applicability of guideline-informing lipid-lowering clinical trials to contemporary real-world patients with atherosclerotic cardiovascular disease

Abstract

Aims Lipid-lowering randomized clinical trials (RCTs) inform guideline recommendations for secondary prevention of atherosclerotic cardiovascular disease (ASCVD). However, these trials were often conducted decades ago using strict eligibility criteria, which may limit their applicability to today's diverse ASCVD population. This study compared clinical characteristics and long-term outcomes between trial-eligible and ineligible real-world ASCVD patients. Methods and results Eligibility criteria from eight pivotal lipid-lowering RCTs were applied to patients with coronary artery disease (CAD), cerebrovascular disease (CeVD), and peripheral artery disease (PAD) in the Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease (UCC-SMART) study (2000-2023). The proportion of patients meeting eligibility criteria was determined for each trial. Differences in clinical characteristics between trial-eligible and ineligible patients were assessed, and risks of recurrent cardiovascular (CV) events and all-cause mortality were compared using cumulative incidence curves with 95% confidence intervals, accounting for competing risks. Among 8537 patients with ASCVD (5673 CAD; 2493 CeVD; 1302 PAD), median follow-up was 8.8 years (interquartile range: 4.2-13.9). Trial eligibility ranged from 9 to 85% for CAD, 7 to 42% for CeVD, and 8 to 78% for PAD. Eligibility was generally higher for earlier trials. Trial-eligible and ineligible patients differed in clinical characteristics in most trials, but their risks of recurrent CV events and all-cause mortality were largely comparable. Conclusion Eligibility of real-world ASCVD patients for lipid-lowering RCTs varied substantially across trials and ASCVD subtypes. Despite differences in clinical characteristics, trial-eligible and ineligible patients generally had comparable outcomes, suggesting that guideline-informing lipid-lowering trials are broadly representative of contemporary real-world ASCVD patients.