Abstract 14916: Adverse Event Reporting in >48,000 Participants in Four Acute Coronary Syndrome Trials

Background: Adverse event (AE) collection in randomized clinical trials establishes the safety of investigational products. Although costly and regulated, it is rarely a topic of study. Methods and Results: Post-discharge AEs were collected per protocol and classified as serious or non-serious in 48,118 participants from 40 countries enrolled in 4 clinical trials of antithrombotic therapy in acute coronary syndromes (APPRAISE-2, PLATO, TRACER, TRILOGY ACS). Pooled data was used to compare patterns and determinants of AE reporting; study endpoints were excluded. Overall, 46.1% of participants had no AEs, 16.3% had at least 1 serious AE (SAE), and another 37.7% had only non-serious AEs (nsAE). A total of 12,266 SAEs and 72,635 nSAEs were reported. AEs were generally well distributed in most system organ classes, including general disorders (11%), infection (10%), gastrointestinal (10%), respiratory (9%), and other (35%), whereas cardiac events were more common among SAEs (14.0% of SAEs, 8.4% of nSAEs). AE rates, particularly non-serious, were highest after hospital discharge, and decreased rapidly during the following 3 months (Figure 1). Using a Cox proportional hazards model, the independent predictors of having an SAE included older age (HR 1.07, 95% CI 1.05-1.09 for every 5-year increase), female sex (HR 1.11, 95% CI 1.03-1.18), and common comorbidities (HF, COPD, Afib, CKD, DM), while enrollment in Asia (HR 0.84, 95% CI 0.75-0.94) or Eastern Europe (HR 0.63, 95% CI 0.58-0.69) predicted fewer SAEs. Conclusions: Most reported AEs are non-serious, non-cardiac, and reported early in follow-up. The high volume of AEs and the significant variation in SAE reporting across patient characteristics and region of enrollment make efforts to focus the approach to AE collection in large trials warranted.