Pretreatment with aspirin in acute coronary syndromes: Lessons from the ACUITY and HORIZONS-AMI trials

Background: Aspirin is promptly administered to patients presenting with acute coronary syndromes. It is not known whether aspirin pretreatment in acute coronary syndrome patients is beneficial, particularly because some, but not all, prior studies identified aspirin pretreatment as an independent risk factor for adverse ischemic events. Objective: To study the effect of aspirin pretreatment in patients with acute coronary syndromes enrolled in two large randomized clinical trials. Methods: Patients enrolled in the ACUITY and HORIZONS-AMI trials were analyzed according to aspirin pretreatment within 5-7 days before acute coronary syndromes. We evaluated the incidence of death, myocardial infarction, target vessel revascularization, stent thrombosis and bleeding at 30 days and 1 year. Multivariable regression analysis was performed for all-cause and cardiac death. Results: Among 17,387 patients, 10,587 (60.9%) were pretreated with aspirin. Pretreated patients were significantly older and more likely to have diabetes mellitus, hypertension and prior revascularization, and receive only medical therapy without revascularization. Aspirin pretreatment was associated with reduced 48-hour cardiac death (adjusted hazard ratio 0.50, 95% confidence interval 0.26-0.97; P=0.04) and 30-day death (adjusted hazard ratio 0.68, 95% confidence interval 0.49-0.94; P=0.04). Myocardial infarction was more frequent in the aspirin pretreatment group at 30 days (P<0.0001), while stent thrombosis was less frequent (P=0.01). A strong interaction was present such that aspirin pretreatment was associated with reduced 30-day death in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS), but not in those with ST-segment elevation myocardial infarction (P=0.001). Conclusions: Among patients with acute coronary syndromes in these two large prospective studies, aspirin pretreatment identified a higher risk cohort and was an independent predictor of reduced mortality at 30 days, especially in patients with NSTEACS.