International variation in management and outcomes in high-risk patients following acute coronary syndromes: results from the APPRAISE-2 trial

Abstract

Purpose: Cardiovascular (CV) disease represents a global problem, yet geographic disparities exist. We describe international variation in contemporary treatment patterns and outcomes in high-risk patients after acute coronary syndrome (ACS). Methods: Using data from APPRAISE-2 (Apixaban for Prevention of Acute Ischemic Events 2), which randomized patients to apixaban or placebo, we examined treatment patterns and outcomes across 5 geographic regions. Cox proportional hazards models sequentially adjusted for patient features and revascularization status were used to assess ischemic and bleeding outcomes. Results: Among 7,392 high-risk patients in APPRAISE-2, more than half (58.7%) were enrolled outside of North America and Western Europe. There were substantial geographic differences in patient demographics (age, sex), comorbidities (diabetes, hypertension, peripheral vascular disease), clinical presentation (heart failure, elevated cardiac markers), and treatment (revascularization). Clinical event rates varied significantly across regions (Table), with the lowest event rates observed in Asia/Australia. Geographic differences persisted after adjustment for all outcomes except CV death. There was no significant interaction between apixaban treatment effect and region for any outcome. Conclusion: In this high-risk post-ACS population, we found global disparities in patient management and outcomes; largely unaccounted for by measured differences in patient characteristics or treatment. Further investigation of temporal trends in regional variability regarding patient recruitment, management, and outcomes across global clinical trials is needed.