Association of type of presentation, STEMI vs NSTEMI/UA, with the relative long-term incidence of cardiovascular and non-cardiovascular mortality

Background: Understanding patient characteristics that may affect relative risk of cardiovascular (CV) versus non-CV death is important for designing clinical trials, since these characteristics differ depending on the type of ACS at presentation and clinical trials often specify various enrichment factors to attempt to enroll higher-risk patients. Methods: IMPROVE-IT was an RCT of simvastatin with either ezetimibe or placebo following ACS; enrollment of STEMI patients was capped at ~1/3 and thus stopped early. Cause of death was adjudicated by an independent clinical events committee. During the interval (2.5 years) the trial was enrolling both STEMI and UA/NSTEMI patients, we compared the cumulative incidence of CV and non-CV death for patients with STEMI and UA/NSTEMI over a 7-year follow-up. Results: In 6024 patients, the presenting event was STEMI for 46% (n=2773) and UA/NSTEMI for 54% (n=3251). Compared with STEMI patients, UA/NSTEMI patients were older (64 vs. 60 years); had lower creatinine clearance (84.0 vs. 87.4 mL/min); and had higher rates of diabetes mellitus (28.2 vs. 18.7%), multi-vessel disease (20.9 vs. 4.3%), and prior MI (24.2 vs. 9.7%). In those who presented with STEMI, the cumulative incidence of CV death was higher for ~3 years following the index event, after which non-CV death predominated (Figure A). In those presenting with UA/NSTEMI, the cumulative incidence of CV death remained higher than non-CV death over the full follow-up period (Figure B). Conclusions: For patients enrolled in IMPROVE-IT, the type of ACS at presentation was associated with differences in the relative incidences of CV and non-CV death over long-term follow-up. To the extent that this finding reflects a higher burden of disease and increased CV risk factors in UA/NSTEMI patients meeting enrollment criteria for IMPROVE-IT, it has potential implications for projecting mortality benefit in ACS trials.