Maurizio Menichelli1, Franz-Josef Neumann2, Gjin Ndrepepa3, Katharina Mayer3, Jochen Wöhrle4, Isabell Bernlochner5, Gert Richardt6, Bernhard Witzenbichler7, Dirk Sibbing8, Senta Gewalt3, Dominick J Angiolillo9, Shqipdona Lahu3, Christian W Hamm10, Alexander Hapfelmeier11, Dietmar Trenk2, Karl-Ludwig Laugwitz12, Heribert Schunkert13, Stefanie Schüpke13, Adnan Kastrati13. 1. Ospedale Fabrizio Spaziani, Cardiology, Frosinone, Italy (M.M.). 2. University Heart Center Freiburg-Bad Krozingen, Bad Krozingen, Germany (F.N., D.T.). 3. Deutsches Herzzentrum München and Technische Universität München, Munich, Germany (G.N., K.M., S.G., S.L.). 4. Medical Campus Lake Constance, Friedrichshafen, Germany (J.W.). 5. Medizinische Klinik und Poliklinik Innere Medizin I (Kardiologie, Angiologie, Pneumologie), Klinikum rechts der Isar, Munich, Germany, and German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Germany (I.B.). 6. Heart Center Bad Segeberg, Bad Segeberg, Germany (G.R.). 7. Helios Amper-Klinikum Dachau, Dachau, Germany (B.W.). 8. Klinik der Universität München, Ludwig-Maximilians-Universität, Munich, Germany, and German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Germany (D.S.). 9. University of Florida College of Medicine, Jacksonville, Florida (D.J.A.). 10. Heart Center, Campus Kerckhoff of Justus-Liebig-University, Giessen, Germany, and German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Germany (C.W.H.). 11. Technical University of Munich, School of Medicine, Institute of Medical Informatics, Statistics and Epidemiology, Munich, Germany (A.H.). 12. Medizinische Klinik und Poliklinik Innere Medizin I, Klinikum rechts der Isar, Munich, Germany, and German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Germany (K.L.). 13. Deutsches Herzzentrum München and Technische Universität München, Munich, Germany, and German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Germany (H.S., S.S., A.K.).
Abstract
BACKGROUND: The 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. OBJECTIVE: To 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). DESIGN: Prespecified analysis of the multicenter, randomized ISAR-REACT 5 trial. SETTING: 23 centers in Germany and Italy. PATIENTS: 3997 patients with ACS planned for invasive management. INTERVENTION: Participants 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). MEASUREMENTS: The efficacy end point was a composite of death, myocardial infarction, or stroke, and the safety end point was bleeding, both at 12 months. RESULTS: In 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). LIMITATION: The study is a subgroup analysis. CONCLUSION:In 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 SOURCE: German Center for Cardiovascular Research and Deutsches Herzzentrum München.
RCT Entities:
BACKGROUND: The 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. OBJECTIVE: To 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). DESIGN: Prespecified analysis of the multicenter, randomized ISAR-REACT 5 trial. SETTING: 23 centers in Germany and Italy. PATIENTS: 3997 patients with ACS planned for invasive management. INTERVENTION: Participants 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). MEASUREMENTS: The efficacy end point was a composite of death, myocardial infarction, or stroke, and the safety end point was bleeding, both at 12 months. RESULTS: In 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). LIMITATION: The study is a subgroup analysis. CONCLUSION: In 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 SOURCE: German Center for Cardiovascular Research and Deutsches Herzzentrum München.
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