Anne H Tavenier1,2, Roxana Mehran1, Mauro Chiarito1, Davide Cao1, Carlo A Pivato1,3,4, Johny Nicolas1, Frans Beerkens1, Matteo Nardin1, Samantha Sartori1, Usman Baber1, Dominick J Angiolillo5, Davide Capodanno6, Marco Valgimigli7,8, Renicus S Hermanides2, Arnoud W J van 't Hof2,9, Jur M Ten Berg9,10, Kiyuk Chang11, Annapoorna S Kini1, Samin K Sharma1, George Dangas1. 1. Center for Interventional Cardiovascular Research and Clinical Trials, The Zena and Michael A. Weiner Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, 1030, New York, NY 10029, USA. 2. Department of cardiology, Isala Heart Center, Zwolle, the Netherlands. 3. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele-Milan, Italy. 4. Humanitas Research Hospital IRCCS, Rozzano-Milan, Italy. 5. Division of cardiology, University of Florida College of Medicine, Jacksonville, FL, USA. 6. Division of cardiology, University of Catania, Catania, Italy. 7. Bern University Hospital, University of Bern, Bern, Switzerland. 8. Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, Lugano, Switzerland. 9. Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands. 10. St. Antonius Hospital, Nieuwegein, the Netherlands. 11. Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Abstract
AIM: Optimal dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) intends to balance ischemic and bleeding risks. Various DAPT de-escalation strategies, defined as switching from a full-dose potent to a reduced dose or less potent P2Y12 inhibitor, have been evaluated in several ACS-PCI trials. We aimed to compare DAPT de-escalation to standard DAPT with full-dose potent P2Y12 inhibitors in ACS patients who underwent PCI. METHODS AND RESULTS: PubMed, Google Scholar, and Cochrane Central Register of Controlled Trials were searched for eligible randomized controlled trials. Aspirin monotherapy trials were excluded. Five randomized trials (n = 10 779 patients) that assigned DAPT de-escalation (genetically guided to clopidogrel n = 1242; platelet function guided to clopidogrel n = 1304; unguided to clopidogrel n = 1672; unguided to lower dose n = 1170) vs. standard DAPT (control group n = 5391) were included in this analysis. DAPT de-escalation was associated with a significant reduction in Bleeding Academic Research Consortium ≥2 bleeding (HR 0.57, 95% CI 0.42-0.78; I2 = 77%) as well as major adverse cardiac events, represented in most trials by the composite of cardiovascular mortality, myocardial infarction, stent thrombosis, and stroke (HR 0.77, 95% CI 0.62-0.96; I2 = 0%). Notwithstanding the limited power, consistency was noted across various de-escalation strategies. CONCLUSION: De-escalation of DAPT after PCI for ACS, both unguided and guided by genetic or platelet function testing (PFT), was associated with lower rates of clinically relevant bleeding and ischemic events as compared to standard DAPT with potent P2Y12 inhibitors based on five open-label RCTs reviewed.
AIM: Optimal dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) intends to balance ischemic and bleeding risks. Various DAPT de-escalation strategies, defined as switching from a full-dose potent to a reduced dose or less potent P2Y12 inhibitor, have been evaluated in several ACS-PCI trials. We aimed to compare DAPT de-escalation to standard DAPT with full-dose potent P2Y12 inhibitors in ACS patients who underwent PCI. METHODS AND RESULTS: PubMed, Google Scholar, and Cochrane Central Register of Controlled Trials were searched for eligible randomized controlled trials. Aspirin monotherapy trials were excluded. Five randomized trials (n = 10 779 patients) that assigned DAPT de-escalation (genetically guided to clopidogrel n = 1242; platelet function guided to clopidogrel n = 1304; unguided to clopidogrel n = 1672; unguided to lower dose n = 1170) vs. standard DAPT (control group n = 5391) were included in this analysis. DAPT de-escalation was associated with a significant reduction in Bleeding Academic Research Consortium ≥2 bleeding (HR 0.57, 95% CI 0.42-0.78; I2 = 77%) as well as major adverse cardiac events, represented in most trials by the composite of cardiovascular mortality, myocardial infarction, stent thrombosis, and stroke (HR 0.77, 95% CI 0.62-0.96; I2 = 0%). Notwithstanding the limited power, consistency was noted across various de-escalation strategies. CONCLUSION: De-escalation of DAPT after PCI for ACS, both unguided and guided by genetic or platelet function testing (PFT), was associated with lower rates of clinically relevant bleeding and ischemic events as compared to standard DAPT with potent P2Y12 inhibitors based on five open-label RCTs reviewed.