Apixaban versus PhenpRocoumon: Oral AntiCoagulation plus antiplatelet tHerapy in patients with Acute Coronary Syndrome and Atrial Fibrillation (APPROACH-ACS-AF): Rationale and design of the prospective randomized parallel-group, open-label, blinded-endpoint, superiority, multicenter-trial of a triple therapy versus a dual therapy in patients with Atrial Fibrillation and Acute Coronary Syndrome undergoing coronary stenting.

Background: A regimen of dual (DAT) vs. triple (TAT) antithrombotic therapy reduces bleeding in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). However, recent evidence suggests that DAT may be associated with an increased ischemic risk. This raises the question whether DAT rather than TAT should be recommended to AF patients that undergo PCI for acute coronary syndrome (ACS), carrying a particularly high risk of both bleeding and ischemic events, studied only as subgroups of previous trials.
Methods and Design: The APPROACH-ACS-AF-(DZHK-7) trial is a multicenter prospective, randomized, open-label, blinded endpoint (PROBE) trial which will include patients presenting with an ACS managed by PCI and requiring oral anticoagulation (OAC) due to AF. The trial will test, whether a DAT-regimen comprising clopidogrel plus the non-Vitamin-K-antagonist oral anticoagulant (NOAC) apixaban is superior to a TAT-regimen of vitamin-K-antagonist (VKA) plus dual anti-platelet therapy (APT) with respect to bleeding. A total of 400 patients will be randomized 1:1 to a control-arm with guideline-recommended TAT with VKA plus clopidogrel and acetylsalicylic-acid and a study arm receiving DAT comprising apixaban plus clopidogrel. Patients will be followed-up for 6 months. The primary endpoint of the study is the cumulative incidence of BARC type ≥2 bleeding, secondary endpoints include a composite clinical ischemic outcome and net clinical outcome.
Conclusions: APPROACH-ACS-AF is the first trial dedicated to ACS patients, testing whether in terms of bleeding a DAT with NOAC is superior to a TAT regimen with VKA in high-risk ACS patients with AF.
Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: D.M.L reports grants from Deutsches Zentrum für Herz-Kreislaufforschung (DZHK), Bayer AG, AstraZeneca, Novartis, Abbott Vascular, Biotronik and Sahajanand Medical Technologies Pvt Ltd. (SMT) and personal fees from Bayer AG, Daiichi Sankyo, Amgen, B.Braun, Abbott Vascular, Boehringer Ingelheim, Boston, Sahajanand Medical Technologies Pvt Ltd. (SMT), Medtronik, Bayer AG, Vifor, Novartis and AstraZeneca; T.G. reports a research grant from Abbott Vascular and neovasc, lecture/consulting fees from Abbott Vascular, Neovasc, Boston Scientific, Daiichi-Sankyo, Bayer, Astra Zeneca, BMS, SMT, Eli Lilly, Pfizer, all outside the submitted work; I.A. reports personal fees from Daiichi Sankyo, Pfizer/BMS, Boston Scientific, GORE Medical; A.A.M. reports personal fees from AMGEN, AtraZeneca, BAYER, Berlin Chemie, Daiichi Sankyo outside the submitted work; M.B. received personal fees from Bayer, Boehringer-Ingelheim, Boston-Scientific, Daiichi-Sankyo, Medtronic, ZOLL CMS; F.E. reports grants from German Research Foundation (DFG), grants from German Ministry of Education and Research, during the conduct of the study; personal fees and non-financial support from Novartis, grants and personal fees from Boehringer Ingelheim, personal fees from CVRx, Pfizer, Medtronic, grants and personal fees from Servier, personal fees from MSD/Bayer, personal fees from Bayer, personal fees from Resmed, personal fees from Berlin Chemie, grants from Thermo Fischer, personal fees from Vifor Pharma, personal fees from PharmaCosmos, personal fees from Merck, outside the submitted work; N.S. received travel grants from BMS/Pfizer outside the submitted work; D.S. reports grants from Roche Diagnostics, grants from Daiichi Sankyo, personal fees from Bayer, personal fees from Astra Zeneca, personal fees from Daiichi Sankyo, personal fees from Eli Lilly, personal fees from MSD, personal fees from Pfizer, and personal fees from Sanofi, outside the submitted work; H.I. reports lecture fees from Bayer, Boehringer, Daichi Sankyo, Pfizer, Bristol-Myers-Squibb, outside the submitted work; T.R reports personal fees from Astra Zeneca, Bayer, Boehringer, Daichi Sankyo, Bristol-Myers-Squibb, Medtronic outside the submitted work; J.M. reports an institutional grant from Boston Scientific, lecture fees from Boston Scientific, Edwards LifeScience, Medtronic, Biotronik, Astra Zeneca, BMS and Terumo, Siemens outside the submitted work; J.H. reports speaker and advisory board activities for Abbott Vascular and Edwards Lifesciences and institutional research support from Abbott Vascular and Edwards Lifesciences outside the submitted work; S.M. received research grants from Roche (Tropical ACS trial) and Pfizer/BMS (APPROACH-ACS-AF trial). S.M. also reports grants from Deutsches Zentrum für Herz-Kreislaufforschung, during the conduct of the study; grants from Pfizer, from Roche, outside the submitted work; R.W. reports grants from Deutsches Zentrum für Herz-Kreislaufforschung, during the conduct of the study. R.W. reports grants from Boston Scientific (MULTASA trial). R.W. reports personal fees from Bayer, Boehringer, Daichi Sankyo, Pfizer, Bristol-Myers-Squibb, Boston Scientific, Biotronik outside the submitted work; L.R., C.S., M.M., A.K., H.B. and U.M. do not have any conflicts of interest.
(© 2021 The Authors.)