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Background: Dual antiplatelet therapy is recommended for patients with acute coronary syndromes (ACS). Approximately 10% to 15% of these patients will undergo coronary artery bypass graft (CABG) surgery for index events, and current guidelines recommend stopping clopidogrel at least 5 days before CABG. This waiting time has clinical and economic implications., Objectives: This study aimed to evaluate if a platelet reactivity-based strategy is noninferior to standard of care for 24-h post-CABG bleeding., Methods: In this randomized, open label noninferiority trial, 190 patients admitted with ACS with indications for CABG and on aspirin and P2Y 12 receptor inhibitors, were assigned to either control group, P2Y 12 receptor inhibitor withdrawn 5 to 7 days before CABG, or intervention group, daily measurements of platelet reactivity by Multiplate analyzer (Roche Diagnostics GmbH, Vienna, Austria) with CABG planned the next working day after platelet reactivity normalization (pre-defined as ≥46 aggregation units)., Results: Within the first 24 h of CABG, the median chest tube drainage was 350 ml (interquartile range [IQR]: 250 to 475 ml) and 350 ml (IQR: 255 to 500 ml) in the intervention and control groups, respectively (p for noninferiority <0.001). The median waiting period between the decision to undergo CABG and the procedure was 112 h (IQR: 66 to 142 h) and 136 h (IQR: 112 to 161 h) (p < 0.001), respectively. In the intention-to-treat analysis, a 6.4% decrease in the median in-hospital expenses was observed in the intervention group (p = 0.014), with 11.2% decrease in the analysis per protocol (p = 0.003)., Conclusions: A strategy based on platelet reactivity-guided is noninferior to the standard of care in patients with ACS awaiting CABG regarding peri-operative bleeding, significantly shortens the waiting time to CABG, and decreases hospital expenses. (Evaluation of Platelet Aggregability in the Release of CABG in Patients With ACS With DAPT; NCT02516267)., Competing Interests: Funding Support and Author Disclosures This study was financed in part by the Coordination for the Improvement of Higher Education Personnel-Brazil (CAPES) – Finance Code 001. Dr. Furtado has received grants and personal fees from AstraZeneca; personal fees from Servier; and grants from EMS, Pfizer, Novo Nordisk, DalCor, Novartis, and Janssen, all outside the submitted work. Dr. Baracioli has received personal fees from Sandoz. Dr. Barbosa has received personal fees from Bayer, Daiichi-Sankyo, and Servier. Dr. Britto has received research grants from Novo Nordisk, DalCor, AstraZeneca, and Novartis. Dr. Farkouh has received research grants from Amgen, Novartis, and Novo Nordisk. Dr. Gurbel has received consultant and/or receives honoraria from Bayer, Merck, Janssen, Medicure, and USWorld Meds; has received grants from the National Institutes of Health, Janssen, Merck, Bayer, Haemonetics, Instrumentation Labs, and Amgen; holds stock or stock options in Merck, Medtronic, and Pfizer; and holds patents in the area of personalized antiplatelet therapy and interventional cardiology. Dr. Nicolau has received personal fees from AMGEN; has received grants from AstraZeneca, Bristol Myers Squibb, CLS Behring, Dalcor, Janssen, NovoNordisk, and Vifor; has received grants and personal fees from Bayer, Novartis, and Sanofi; and has received personal fees from Daiichi-Sankyo and Servier. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)