Clinical question: Is the treatment strategy with ticagrelor superior to prasugrel in acute coronary syndrome (ACS) with planned invasive evaluation at one year?
Background: Dual antiplatelet therapy is the standard treatment for ACS (acute ST-elevation myocardial infarction (STEMI), acute non-ST-elevation myocardial infarction (NSTEMI), and unstable angina (UA)). Prasugrel and ticagrelor are third generation thienopyridines with more rapid and consistent platelet inhibition and proven superiority over clopidogrel in ACS in previous trials. In STEMI both drugs require a pretreatment loading dose before angiography, In NSTEMI, the pretreatment dose for prasugrel is not needed. Benefits in pre-PCI platelet inhibition in NSTEMI, and ticagrelor over clopidogrel were seen in the PLATO trial. The lack of superiority of prasugrel over clopidogrel was seen in the TRILOGY ACS trial.
Study design: Investigator-initiated, multicenter, randomized, open-label clinical trial. Ticagrelor (loading immediately after randomization) or prasugrel (loading after randomization in STEMI, but after angiogram and before percutaneous coronary intervention in NSTEMI) were assigned in a 1:1 ratio. Where indicated, conservative therapy of aspirin plus the trial medication was prescribed. All patients were followed at one, six, and 12 months. The primary endpoint was the composite at one year of myocardial infarction, stroke, or death from any cause. The secondary safety endpoint was the incidence of bleeding.
Setting: 21 centers in Germany and two centers in Italy
Synopsis: 4,018 patients were enrolled (41.1% STEMI, 46.2% NSTEMI, and 12.7% UA). 2,012 were assigned to ticagrelor and 2,006 to prasugrel. 84.1% underwent percutaneous coronary intervention, and 2.1% received coronary artery bypass grafts. About 81% were discharged on trial medication. At one year, 15.2% had stopped ticagrelor, and 12.5% had stopped prasugrel. All but 90 patients (41 ticagrelor, 49 prasugrel) completed follow-up (83% by phone, 10% in clinic, and 7% by letter). A primary endpoint event occurred in 9.3% of the ticagrelor versus 6.9% in the prasugrel group (P=0.006): death, 4.5% versus 3.7%; myocardial infarction, 4.8% versus 3%; stroke, 1.1% versus 1.0%. Definite or probable stent thrombosis occurred in 1.3% versus 1.0% and definite stent thrombosis in 1.1% versus 0.6%. Major bleeding was seen in 5.4% of the ticagrelor versus 4.8% in the prasugrel group (P=0.46). Limitations are open-label design, and the majority of follow-ups were completed by phone.
Bottom line: Prasugrel was superior to ticagrelor at one-year follow-up in ACS with planned invasive evaluation, with a significantly lower composite endpoint of death, MI, or stroke and a similar incidence of major bleeding.
Citation: Schupke S, Neumann F, et al. Ticagrelor or prasugrel in patients with acute coronary syndromes. N Engl J Med. 2019;381(16):1524-34.
Ms. Peney
Ms. Penev is a physician assistant in the heart transplant and mechanical circulatory support program at Stanford Health Care in Palo Alto, Calif.