• Maurizio Menichelli, Franz-Josef Neumann, Gjin Ndrepepa, Katharina Mayer, Jochen Wöhrle, Isabell Bernlochner, Gert Richardt, Bernhard Witzenbichler, Dirk Sibbing, Senta Gewalt, Dominick J Angiolillo, Shqipdona Lahu, Christian W Hamm, Alexander Hapfelmeier, Dietmar Trenk, Karl-Ludwig Laugwitz, Heribert Schunkert, Stefanie Schüpke, and Adnan Kastrati.
• Ospedale Fabrizio Spaziani, Cardiology, Frosinone, Italy (M.M.).
• Ann. Intern. Med. 2020 Sep 15; 173 (6): 436-444.

BackgroundThe efficacy and safety of a reduced dose of prasugrel versus a standard dose of ticagrelor in elderly patients or those with a low body weight presenting with an acute coronary syndrome (ACS) are unknown.ObjectiveTo investigate the effect of an age- and weight-adapted dose of prasugrel versus a standard dose of ticagrelor in patients with ACS. (ClinicalTrials.gov: NCT01944800).DesignPrespecified analysis of the multicenter, randomized ISAR-REACT 5 trial.Setting23 centers in Germany and Italy.Patients3997 patients with ACS planned for invasive management.InterventionParticipants were randomly assigned to receive a standard dose of ticagrelor or prasugrel (reduced dose in the elderly or low-weight group and standard dose in the neither elderly nor low-weight group).MeasurementsThe efficacy end point was a composite of death, myocardial infarction, or stroke, and the safety end point was bleeding, both at 12 months.ResultsIn the elderly or low-weight group, the efficacy end point occurred in 12.7% of patients assigned to receive prasugrel and 14.6% of those assigned to receive ticagrelor (hazard ratio [HR], 0.82 [95% CI, 0.60 to 1.14]); in the neither elderly nor low-weight group, the efficacy end point occurred in 4.8% of patients assigned to receive prasugrel and 7.3% of those assigned to receive ticagrelor (HR, 0.65 [CI, 0.48 to 0.88]; P for interaction > 0.2). In the elderly or low-weight group, Bleeding Academic Research Consortium type 3 to 5 bleeding occurred in 8.1% of patients assigned to receive prasugrel and 10.6% of those assigned to receive ticagrelor (HR, 0.72 [0.46 to 1.12]), and in 3.7% and 3.8%, respectively, of patients in the neither elderly nor low-weight group (HR, 0.98 [CI, 0.65 to 1.47]; P for interaction > 0.2).LimitationThe study is a subgroup analysis.ConclusionIn elderly or low-weight patients with ACS, a reduced dose of prasugrel compared with the standard dose of ticagrelor is associated with maintained anti-ischemic efficacy while protecting these patients against the excess risk for bleeding.Primary Funding SourceGerman Center for Cardiovascular Research and Deutsches Herzzentrum München.

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