Antithrombotic Alone for Chronic Coronary Heart Disease and Nonvalvular Atrial Fibrillation

Expert Comment

Gheorghe-Andrei Dan, Bucharest, Romania
ISCP Board of Directors

Up to 30% of AF patients presents with both acute coronary syndrome and/or need for PCI. This implies the combination of double antiplatelet therapy (DAPLT) proven to be superior to aspirin alone in preventing stent thrombosis with anticoagulant therapy, essential for the prevention of ischemic events, especially stroke.1 Several smaller studies indicated that omitting ASA (WOEST) or shortening the duration of triple therapy (ISAR -TRIPLE) in patients taking warfarin is associated with increased safety without diminished efficacy.2 RE-DUAL study demonstrated the safety superiority of double antithrombotic therapy (DAT) compared with triple therapy (TAT) including warfarin with dabigatran and clopidogrel in patients undergoing PCI irrespective of type of presentation (chronic or acute coronary syndrome). The PIONEER AF-PCI study has shown also the superiority of DAT including rivaroxaban concerning bleeding with a reduced risk of total bleeding events and recurrent hospitalization for adverse events without decreasing the ischemic efficacy (however underpowered for this endpoint). The more recent AUGUSTUS trial with a 2×2 factorial design compared warfarin vs apixaban in patients receiving a P2Y12 inhibitor (mostly clopidogrel) with or without ASA. Less bleeding was demonstrated in DAT versus TAT and in apixaban treated patients versus warfarin. A recent metanalysis confirmed a reduction by 47% of the TIMI major and minor bleeding risk.3

Less is known about safety and efficacy of single anticoagulant therapy in patients with chronic coronary disease (more than 1 year after PCI) versus combination with ASA. The importance of the problem resides also in the fact that the combination is largely used in practice at the expense of increasing bleeding.4 The issue was investigated in the AFIRE trial (Atrial Fibrillation and Ischemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease).5 The open study included 2236 Japanese patients with a previous PCI more than 1year earlier or without revascularization however with documented coronary obstruction comparing rivaroxaban monotherapy versus rivaroxaban plus ASA. The study was stopped prematurely because of excess of bleeding in the combination arm. The primary efficacy end point was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause. Rivaroxaban alone proved noninferiority versus DAT (HR 0.72, 95% CI 0.55-0.95, p for non-inferiority < 0.001). Rivaroxaban alone was superior versus DAT in the safety end point of major ISTH bleeding risk (HR, 0.59, 95% CI 0.39 to 0.89; p = 0.01 for superiority). It is well known that late after acute coronary events and/or PCI the thrombotic risk depends more on coagulation cascade than in early stages where the platelet thrombus predominates. This was also one of the explanations of the positive results in the COMPASS trial. It results that in patients with AF and chronic coronary disease anticoagulation alone is safer and as efficient compared with combination of anticoagulant with ASA.


  1.  Neumann F-J, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J [Internet]. 2019 Jan 7 [cited 2020 Jan 8];40(2):87–165. 
  2. Capodanno D, Huber K, Mehran R, Lip GYH, Faxon DP, Granger CB, et al. Management of Antithrombotic Therapy in Atrial Fibrillation Patients Undergoing PCI. J Am Coll Cardiol [Internet]. 2019 Jul 9 [cited 2020 Jan 8];74(1):83–99. 
  3.  Golwala HB, Cannon CP, Steg PG, Doros G, Qamar A, Ellis SG, et al. Safety and efficacy of dual vs. triple antithrombotic therapy in patients with atrial fibrillation following percutaneous coronary intervention: a systematic review and meta-analysis of randomized clinical trials. Eur Heart J [Internet]. 2018 May 14 [cited 2020 Jan 9];39(19):1726-1735a. 
  4. Lip GYH, Laroche C, Boriani G, Dan G-A, Santini M, Kalarus Z, et al. Regional differences in presentation and treatment of patients with atrial fibrillation in Europe: a report from the EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot General Registry. Europace [Internet]. 2015 Feb 1 [cited 2020 Jan 9];17(2):194–206. 
  5. Yasuda S, Kaikita K, Akao M, Ako J, Matoba T, Nakamura M, et al. Antithrombotic Therapy for Atrial Fibrillation with Stable Coronary Disease. N Engl J Med [Internet]. 2019 Sep 19 [cited 2020 Jan 8];381(12):1103–13.