Rationale: Dual antiplatelet therapy is crucial in patients with an acute coronary syndrome (ACS) to prevent artherothrombotic events. The recent guideline of the European Society of Cardiology (ESC) recommends the use of more potent antiplatelet drugs i.e. ticagrelor or prasugrel, which also give more bleeding complications. The “Commissie Farmaceutische Hulp” (CFH) concluded that ticagrelor is superior to clopidogrel, mainly because of a mortality reduction observed in the PLATO study. However, the representation of the elderly in clinical trials is low. In a subgroup analysis of patients 75 years of age and older, the difference between cardiovascular event rates in ticagrelor versus clopidogrel treated patients, did not reach statistical significance. There is a major gap in the knowledge regarding the optimal strategy for the elderly, who have an increased risk of both artherothrombotic and bleeding complications. The ESC guideline advises on the use of the CRUSADE risk score for risk stratification. However, based on the currently available data it is not clear which antiplatelet treatment should be initiated in those patients with a high bleeding risk, who also appear to have the highest atherothrombotic risk.
Objectives: To assess the safety, efficacy and net clinical benefit of clopidogrel versus the new antiplatelet drugs i.e. ticagrelor and prasugrel.
Study design: Randomized, controlled, open label, multicenter study.
Study population: 1,000 patients hospitalized for either myocardial infarction without ST-segment elevation (NSTEMI) or unstable angina, aged at least 75 years and with a score of at least 30.1 based on the CRUSADE bleeding risk score.
Intervention: Patients randomized to clopidogrel will receive 75 mg daily for one year. Those randomized to the new antiplatelet drugs will be treated with either ticagrelor 90 mg twice daily or prasugrel 5 mg daily, according to hospital’s local standards. The follow-up duration will be 1 year.
Outcome measures: Safety in terms of non CABG related PLATO major and minor bleedings, efficacy in terms of the combined endpoint of death, myocardial infarction, stroke, stent thrombosis, the net clinical benefit defined as the combined safety and efficacy endpoint, quality of life assed by the EuroQol 5D and SF36 questionnaires.
Sample size calculation/data analysis: Assuming an alpha of 0.05, beta 0.8 and the combined end point of non-CABG related PLATO major and minor bleedings of 10% in the clopidogrel group versus 17% in the new antiplatelet drugs group, a lost-to-follow rate of 10%, the inclusion of 1,000 patients (500 per group) would be sufficient. Intention-to-treat principle will be used in data analysis. Kaplan-Meier analysis will be used and groups will be compared by hazard ratios and 95% confidence intervals. Quality Adjusted Life Years (QALYs) will be calculated.