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TOPLINE:

In patients with acute or chronic coronary syndrome who underwent invasive management, prasugrel was associated with the most favorable balance between efficacy and safety, with lower odds of major adverse cardiovascular events (MACE) and no increase in risk for major bleeding.

METHODOLOGY:

• Researchers conducted a systematic review and network meta-analysis of randomized clinical trials to compare the efficacy and safety of oral P2Y12 inhibitors after percutaneous coronary intervention.
• They searched PubMed and Embase through November 2025 and included randomized clinical trials in adults with acute or chronic coronary syndrome who underwent an invasive management strategy.
• In the included trials, patients were randomly assigned to receive clopidogrel, prasugrel, or ticagrelor, with dosing according to the protocol of each trial and approved labeling.
• The primary efficacy outcome was the occurrence of MACE, while the primary safety outcome was major bleeding. Secondary outcomes included myocardial infarction, stent thrombosis, and all-cause mortality.
• Researchers compared the outcomes for prasugrel and ticagrelor with those for clopidogrel and pooled the evidence to rank the three drugs based on their overall balance of efficacy and safety.

TAKEAWAY:

• The analysis included 15 trials involving 48,904 patients (mean age, 63.2 years; 27.3% women) and a mean follow-up of 12.1 months. Of these, 24.8% received prasugrel, 32.8% received ticagrelor, and 42.4% received clopidogrel.
• Patients who received prasugrel were less likely to experience MACE than those who received clopidogrel (odds ratio [OR], 0.80; 95% CI, 0.69-0.93) and those who received ticagrelor (OR, 0.83; 95% CI, 0.70-0.98), with lower odds of myocardial infarction and stent thrombosis. Ticagrelor and clopidogrel showed no difference in this outcome.
• Ticagrelor was associated with a higher risk for major bleeding than clopidogrel (OR, 1.24; 95% CI, 1.01-1.52), with increased odds of intracranial hemorrhage. Prasugrel was not linked to higher odds of major bleeding than clopidogrel, and odds did not differ significantly between ticagrelor and prasugrel.
• Prasugrel ranked first for overall balance between efficacy and safety. The three drugs did not differ in risks for all-cause mortality, ischemic stroke, or cardiovascular mortality, although estimates favored prasugrel and ticagrelor for cardiovascular mortality.

IN PRACTICE:

“Prasugrel provided the optimal balance between efficacy and safety,” the researchers concluded.

SOURCE:

The study was led by Muhammad H. Maqsood, MD, MS, of the Houston Methodist Hospital in Houston. It was published online on May 27 in JAMA Cardiology.

LIMITATIONS:

Researchers could not assess the timing or predictors of outcomes from this trial-level analysis of published data without patient-level detail. The definitions of outcomes varied across trials. The analysis used an intention-to-treat approach and did not account for crossovers of treatment.

DISCLOSURES:

The authors did not report any specific source of funding for the study. One author reported receiving personal fees from multiple cardiovascular care and healthcare companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.