Key result
Ticagrelor resulted in a higher 1-year risk of death, MI, or stroke compared to prasugrel in patients with NSTE-ACS (8.7% vs 6.3%; HR 1.41, 95% CI 1.04-1.90).
Why the study?
Current guidelines recommend intensified platelet inhibition by prasugrel or ticagrelor in UA or NSTEMI, but the relative benefits and risks of ticagrelor compared with prasugrel in NSTE-ACS with planned invasive management needed investigation.
Does ticagrelor compared to prasugrel improve clinical outcomes in patients with NSTE-ACS undergoing planned invasive management?
RCT (n=2,365)
Does ticagrelor compared to prasugrel improve clinical outcomes in patients with NSTE-ACS undergoing planned invasive management?
In patients with NSTE-ACS planned for invasive management, prasugrel was superior to ticagrelor in reducing the 1-year risk of death, MI, or stroke without increasing major bleeding.
Answers are grounded in this paper and cite their sources.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“A shift from ticagrelor to prasugrel occurred in Denmark following the findings of the ISAR-REACT 5 trial and the updated ESC guideline recommendation favoring prasugrel. In 2019, more than 99% of patients received ticagrelor; by 2022, 89% received prasugrel.”
Ticagrelor associated with higher ischemic events than prasugrel; leaves open whether this reflects confounding or a true difference.
BACKGROUND Current guidelines recommend intensified platelet inhibition by prasugrel or ticagrelor in patients with unstable angina (UA) or non-ST-segment elevation (NSTE) myocardial infarction (MI). OBJECTIVES This study sought to investigate the benefits and risks of ticagrelor as compared with prasugrel in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and planned invasive management. METHODS This post hoc analysis combines the pre-specified subgroups of UA and NSTEMI of the randomized ISAR-REACT 5 trial. It included 1,179 patients assigned to ticagrelor and 1,186 assigned to prasugrel. Ticagrelor was started immediately after randomization and prasugrel after coronary angiography. The primary endpoint was a composite of death, MI, or stroke during 1-year follow-up, and the safety endpoint was Bleeding Academic Research Consortium class 3-5. RESULTS The primary endpoint was reached in 101 (8.7%) patients in the ticagrelor and in 73 (6.3%) patients in the prasugrel group (hazard ratio [HR]: 1.41; 95% confidence interval [CI]: 1.04 to 1.90). The HR for all-cause death was 1.43 (95% CI: 0.93 to 2.21) and that for MI 1.43 (95% CI: 0.94 to 2.19). The safety endpoint occurred in 49 (5.2%) patients in the ticagrelor and in 41 (4.7%) patients in the prasugrel group (HR: 1.09; 95% CI: 0.72 to 1.65). Landmark analysis revealed persistence of the efficacy advantage with prasugrel after the first month. CONCLUSIONS In patients with NSTE-ACS, we found that prasugrel was superior to ticagrelor in reducing the combined 1-year risk of death, MI, and stroke without increasing the risk of bleeding. Due to the post hoc nature of the analysis, these findings need confirmation by further studies. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome; NCT01944800).
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Valina et al. (2020) conducted an RCT in Non-ST-segment elevation acute coronary syndromes (NSTE-ACS) (n=2,365). Ticagrelor vs. Prasugrel was evaluated on Composite of death, MI, or stroke (HR 1.41, 95% CI 1.04 to 1.90). Ticagrelor resulted in a higher 1-year risk of death, MI, or stroke compared to prasugrel in patients with NSTE-ACS (8.7% vs 6.3%; HR 1.41, 95% CI 1.04-1.90).
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