Prasugrel Betters Ticagrelor in Cardiovascular Event Risk Among ACS Patients


Findings from ISAR-REACT 5 show a treatment strategy involving prasugrel significantly reduces patient risk of death, myocardial infarction, or stroke when compared to the other antiplatelet therapy.

Prasugrel was associated with significantly lower incidence of death, myocardial infarction, or stroke among patients presenting with acute coronary syndromes than ticagrelor.

In new findings from the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary (ISAR-REACT) 5 Trial—presented at the European Society of Cardiology (ESC) Congress 2019 in Paris—investigators found limited difference in safety outcomes between the pair of class 1-recommended therapies for acute coronary syndromes in patients with or without ST-segment elevation.

However, there were significant differences between the 2 therapies in major outcome events associated with the condition which inflicts approximately 1 million Americans annually.

Led by Stefanie Schupke, MD, of the Department of Cardiology at the German Heart Center Munich, investigators sought data on the merits of one-year treatment with ticagrelor versus prasugrel in patients with acute coronary syndromes for whom invasive evaluation is planned.

“Notably, the loading strategies of ticagrelor and prasugrel are different in patients who have acute coronary syndromes without ST-segment elevation,” investigators noted. Ticagrelor is generally used as a preceding therapy to diagnostic angiography, while prasugrel is only administered following diagnostic angiography—as no evidence of its benefit for pre-treatment care has been observed.

Schupke and colleagues conducted the multicenter, randomized, open-label trial with 4018 patients who presented with acute coronary syndromes and for whom invasive evaluation was planned. The team assessed for a primary endpoint of composite of death, myocardial infarction, or stroke at 1 year, with a major secondary safety endpoint of patient bleeding.

Investigators observed a primary endpoint event occurring in 184 (9.3%) of ticagrelor patients, and just 137 (6.9%) of prasugrel patients (HR, 1.36; 95% CI, 1.09-1.79; P= .006). Individually, death (4.5% vs 3.7%), myocardial infarction (4.8% vs 3.0%), and stroke (1.1% vs 1.0%) incidences were each respectively greater in patients administered ticagrelor.

Definite or probably stent thrombosis was also more frequent in patients administered ticagrelor versus prasugrel (1.3% vs 1.0%), as was definite stent thrombosis (1.1% vs 0.6%).

As defined by the Bleeding Academic Research Consortium scale, major bleeding was observed in 5.4% of the ticagrelor treatment arm and 4.8% of the prasugrel treatment arm (HR, 1.12; 95% CI, 0.83-1.51; P= .46).

Investigators emphasized these findings do not simply just reflect a comparison of 2 different antiplatelet therapies—but rather, a pair of antiplatelet treatment strategies involving 2 different drugs. Their hypothesis that a ticagrelor-based strategy would be superior to one based on prasugrel—one evidenced by several other considerations—proved incorrect.

“An unexpected finding was that the risk of ischemic events at 1 year after randomization in the ISAR-REACT 5 trial was significantly lower in the prasugrel group than in the ticagrelor group,” investigators wrote. “The finding of a lower incidence of the primary end point in the prasugrel group than in the ticagrelor group was not anticipated during the sample-size calculation. The incidence of myocardial infarction was lower in the present trial than in previous pivotal trials.”

Though the open-label nature of the trial served as a limitation to its results—and that most patient follow-up was conducted over the phone and not face-to-face—investigators concluded patients presenting with acute coronary syndromes, with or without ST-segment elevation, report significantly lower composite incidence of death, myocardial infarction or stroke when treated with prasugrel than ticagrelor.

The study, “Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes,” was published online in The New England Journal of Medicine.

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