Reply to: Dual vs. triple antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention

This commentary refers to ‘Is triple antithrombotic therapy, or rather its duration and composition, the true culprit for the excess of bleeding events observed in patients with atrial fibrillation undergoing coronary intervention?’, by F. Gragnano et al., on page 216. We appreciate the interest by Gragnano et al.1 in our paper. The first point raised by the authors is variability in the duration of triple antithrombotic therapy (TAT) and the relation to bleeding. While we agree that longer duration of TAT is related to increased risk of bleeding, abbreviating the duration may not confer complete protection. This is illustrated by the Kaplan–Meier curves for bleeding in the WOEST trial, which demonstrate separation from day one post-randomization to TAT vs. dual antithrombotic therapy (DAT).2 Furthermore, in the ISAR-TRIPLE trial, examination of the landmark analysis with more sensitive markers of bleeding according to the BARC definition types one to five found that 13.1% of patients in the 6-week TAT group and 21.8% in the 6-month TAT group experienced bleeding [hazard ratio (HR) 0.57, 95% confidence interval 0.37–0.88].3 Of note, even with 6 weeks of TAT, a substantial proportion of the bleeding will have occurred. The second point raised by the authors is related to the possible increased incidence of stent thrombosis (ST) in the DAT group. In response, our analysis demonstrated that the difference in ST was statistically non-significant [HR 1.00, 95% credible interval (CrI) 0.32–2.82]. In addition, ST appeared to be been driven by inclusion of both doses of dabigatran (110 mg and 150 mg b.i.d.) used in RE-DUAL.1 A more intricate analysis included in our supplement using dabigatran 150 mg b.i.d. demonstrates no difference in the rate of ST (HR 0.80, 95% CrI 0.31–2.14).1 Hence, outside of randomized clinical trials and in the absence of further data, we believe that in most patients with atrial fibrillation undergoing percutaneous coronary intervention, discharge on DAT should be the default strategy.4,5 Finally, trials such as MASTER DAPT, ENTRUST AF-PCI, and AUGUSTUS may help us address some of the complexities involved in the management of such patients. Conflict of interest: C.P.C. reports : Research Grants from (all >10K) Amgen, Boehringer-Ingelheim (BI), Bristol-Myers Squibb (BMS), Daiichi Sankyo, Janssen, Merck; Consulting fees from Alnylam, Amarin, Amgen, BI*, BMS, Eisai, Janssen, Kowa, Merck, Pfizer, Regeneron, Sanofi* (* denotes >10K); D.L.B. discloses the following relationships—Advisory Board: Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care, TobeSoft; Chair: American Heart Association Quality Oversight Committee; Data Monitoring Committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic, Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Vice-Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Abbott, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Idorsia, Ironwood, Ischemix, Lilly, Medtronic, PhaseBio, Pfizer, Regeneron, Roche, Sanofi Aventis, Synaptic, The Medicines Company; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); Site Co-Investigator: Biotronik, Boston Scientific, St. Jude Medical (now Abbott), Svelte; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Merck, Novo Nordisk, PLx Pharma, Takeda. The other author declared no conflict of interest.