DOACs and DAPT: A Troubling Combination or a Recipe for Success?


A recently-published study explores the outcomes associated with the combination of DOACs and dual anti platelet therapy.

Patients with both atrial fibrillation (AF) and recent coronary artery stenting present health care providers with a consternating clinical conundrum.

Dual antiplatelet therapy (DAPT) with aspirin (ASA) and a P2Y12 receptor antagonist is required to maintain stent patency; however, this regimen is inferior to warfarin monotherapy for preventing stroke in AF. Likewise, oral anticoagulation with warfarin and aspirin is insufficient to protect against stent thrombosis. Hence patients with both AF and newly-placed coronary artery stents often end up on a regimen of triple therapy (ASA, warfarin, and a P2Y12 receptor antagonist), which markedly increases bleeding risk. The direct acting oral anticoagulants (DOACs), like rivaroxaban and dabigatran, have emerged as safe and effective alternatives to warfarin for stroke prevention in AF patients. To date, the potential role of the DOACs as part of a triple therapy regimen has not been studied.

The PIONEER AF-PCI trial randomly assigned 2124 patients with both AF and recent percutaneous coronary intervention (PCI) to one of 3 regimens:

  • Group 1: Rivaroxaban 15 mg (10 mg if creatinine clearance 30-50 cc/min) daily plus P2Y12 inhibitor monotherapy for 12 months (n = 709).
  • Group 2: Rivaroxaban 2.5 mg twice daily plus DAPT for 1, 6, or 12 months (n = 709). After completion of the 1 or 6 months of DAPT, patients received rivaroxaban 15 mg daily plus low-dose aspirin monotherapy.
  • Group 3: Warfarin plus DAPT for 1, 6, or 12 months (n = 706). After completion of 1 or 6 months of DAPT, patients received warfarin plus low-dose aspirin monotherapy.

There are some other key points regarding this study that are worth mentioning:

  • Most of these were stable patients. ST-segment elevation myocardial infarction (STEMI) only accounted for 12% of the enrolled patients, while non-STEMI was 19%, and unstable angina was 21%.
  • Most patients were on clopidogrel (93%) as the P2Y12 receptor antagonist.
  • Most received a drug-eluting stent (DES) 65%; only 33% received a bare-metal stent (BMS).

The primary outcome, incidence of clinically significant bleeding, occurred in 16.8% of group 1 vs. 18.0% of group 2 vs. 26.7% of group 3 (hazard ratio [HR] 0.59, P < .001 for group 1 vs. 3; HR 0.63, P < .001 for group 2 vs. 3).

In a separate post hoc analysis of the trial published in Circulation, combined all-cause mortality or hospitalization was reduced in the rivaroxaban groups compared to the warfarin control (group 3), with an advantage in both group 1 (34.9% versus 41.9%, HR 0.79, 95% CI 0.66-0.94, number needed to treat=15) and group 2 (31.9% versus 41.9%, HR 0.75, 95% CI 0.62-0.90, number needed to treat=10).

The trial was limited in several ways. The duration of DAPT was nonrandomized and determined by provider discretion. For example, in the 1-month stratum, 67% received a BMS, while in the 12-month stratum, 72% received a DES.

The trial was also underpowered to detect a difference in key efficacy endpoints, like ischemic stroke and stent thrombosis. This is a critical limitation given that the doses of rivaroxaban used in both groups are lower than those approved in the US to prevent stroke in AF. The rivaroxaban 2.5 mg twice daily combined with DAPT was taken from the ATLAS TIMI 51 trial, which established the efficacy of this regimen against DAPT in ACS patients (not AF patients). However, this trial was fraught with issues related to data integrity, and as such the FDA has not approved this dose for secondary prevention in ACS patients.

In light of these limitations, I find it hard to translate anything meaningful from this trial to my own clinical practice. As the rivaroxaban arms were both underdosed, I’m not surprised by the decrease in major bleeding events. Likewise, given the lack of power to evaluate key efficacy endpoints, I fear the using a regimen of lower dose rivaroxaban with either DAPT or antiplatelet monotherapy may expose patients to excessive risk of harm from either ischemic stroke or stent thrombosis (or both).

I will hence not be shifting my patients who require triple therapy to a regimen studied in PIONEER AF-PCI. For these patients, I would continue to advocate warfarin-based anticoagulation with the shortest possible duration of DAPT according to the type of stent placed.


  • Gibson CM, Mehran R, Bode C, et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med. 2016; DOI: 10.1056/NEJMoa1611594.
  • Gibson CM, Pinto DS, Chi G, et al. Recurrent hospitalization among patients with atrial fibrillation undergoing intracoronary stenting treated with 2 treatment strategies of rivaroxaban or a dose-adjusted oral vitamin K antagonist treatment strategy. Circulation. 2016; DOI: 10.1161/CIRCULATIONAHA.116.025783.
  • Krantz MJ, Kaul S. The ATLAS ACS 2—TIMI 51 Trial and the Burden of Missing Data. J Am Coll Cardiol. 2013;62:777—81.

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