Prasugrel use and clinical outcomes by age among patients undergoing PCI for acute coronary syndrome: from the PROMETHEUS study

Background: Prasugrel is a potent thienopyridine that may be preferentially used in younger patients with lower bleeding risk. Objective: We compared prasugrel use and outcomes by age from the PROMETHEUS study. We also assessed age-related trends in treatment effects with prasugrel versus clopidogrel. Methods: PROMETHEUS was a multicenter acute coronary syndrome (ACS) percutaneous coronary intervention (PCI) registry. We compared patients in age tertiles (T1 < 60 years, T2 60–70 years, T3 > 70 years). Major adverse cardiac events (MACE) were a composite of death, myocardial infarction, stroke or unplanned revascularization. Data were adjusted using multivariable Cox regression for age-related risks and propensity score stratification for thienopyridine effects. Results: The study included 19,914 patients: 7045 (35.0%) in T1, 6489 (33.0%) in T2 and 6380 (32.0%) in T3. Prasugrel use decreased from T1 to T3 (29.2% vs. 23.5% vs. 7.5%, p < 0.001). Crude 1-year MACE rates were highest in T3 (17.4% vs. 16.8% vs. 22.7%, p < 0.001), but adjusted risk was similar between the groups (p-trend 0.52). Conversely, crude incidence (2.8% vs. 3.8% vs. 6.9%, p < 0.001) and adjusted bleeding risk were highest in T3 (HR 1.24, 95% CI 0.99–1.55 in T2; HR 1.83, 95% CI 1.46–2.30 in T3; p-trend < 0.001; reference = T1). Treatment effects with prasugrel versus clopidogrel did not demonstrate age-related trends for MACE (p-trend = 0.91) or bleeding (p-trend = 0.28). Conclusions: Age is a strong determinant of clinical risk as well as prasugrel prescription in ACS PCI with much lower use among older patients. Prasugrel did not have a differential treatment effect by age for MACE or bleeding. Graphic abstract: Frequency of prasugrel use and age-related temporal risks of all-cause death and bleeding after ACS PCI.[Figure not available: see fulltext.].