Periprocedural Outcomes of Direct Oral Anticoagulants Versus Warfarin in Nonvalvular Atrial Fibrillation

Circulation. 2018 Oct 2;138(14):1402-1411. doi: 10.1161/CIRCULATIONAHA.117.031457.


Background: Direct oral anticoagulants (DOACs) are surpassing warfarin as the anticoagulant of choice for stroke prevention in nonvalvular atrial fibrillation. DOAC outcomes in elective periprocedural settings have not been well elucidated and remain a source of concern for clinicians. The aim of this meta-analysis was to evaluate the periprocedural safety and efficacy of DOACs versus warfarin in patients with nonvalvular atrial fibrillation.

Methods: We reviewed the literature for data from phase III randomized controlled trials comparing DOACs with warfarin in the periprocedural period among patients with nonvalvular atrial fibrillation. Substudies from 4 trials (RE-LY [Randomized Evaluation of Long-Term Anticoagulation Therapy], ROCKET AF [Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation], ARISTOTLE [Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation], and ENGAGE-AF [Effective Anticoagulation With Factor xA Next Generation in Atrial Fibrillation]) were included in the meta-analysis. DOACs as a group and warfarin were compared in terms of the 30-day pooled risk for stroke/systemic embolism, major bleeding, and death, according to whether the study drug was interrupted or not periprocedurally. The overall relative risk (RR) was estimated with a random-effects model. The I2 test was used to assess heterogeneity in RR among the studies.

Results: In the uninterrupted anticoagulant strategy, there were no differences in the rates of stroke/systemic embolism (pooled risk, 0.6% [29 events/4519 procedures] versus 1.1% [31/2971]; RR, 0.70; 95% confidence interval [CI], 0.41-1.18) and death (1.4% versus 1.8%; RR, 0.77; 95% CI, 0.53-1.12) between DOACs and warfarin and significantly fewer major bleeding events (2.0% versus 3.3%; RR, 0.62; 95% CI, 0.47-0.82) with DOACs compared to warfarin. Under an interrupted strategy, there was no significant difference between DOACs versus warfarin for stroke/systemic embolism (0.4% [41/9260] versus 0.5% [31/7168]; RR, 0.95; 95% CI, 0.59-1.55), major bleeding (2.1% versus 2.0%; RR, 1.05; 95% CI, 0.85-1.30), and death (0.7% versus 0.6%; RR, 1.24; 95% CI, 0.76-2.04). The studies were homogeneous ( I2=0.0%) for all calculated pooled associations except for the RR of death in the interrupted strategy ( I2=26.3%).

Conclusions: The short-term safety and efficacy of DOACs and warfarin are not different in patients with nonvalvular atrial fibrillation periprocedurally. Under an uninterrupted anticoagulation strategy, DOACs are associated with a 38% lower risk of major bleeding compared with warfarin.

Keywords: anticoagulants; atrial fibrillation; heparin; perioperative care; warfarin.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / mortality
  • Clinical Trials, Phase III as Topic
  • Drug Administration Schedule
  • Female
  • Hemorrhage / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Perioperative Care / adverse effects
  • Perioperative Care / methods*
  • Perioperative Care / mortality
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors
  • Stroke / diagnosis
  • Stroke / mortality
  • Stroke / prevention & control*
  • Surgical Procedures, Operative* / adverse effects
  • Surgical Procedures, Operative* / mortality
  • Time Factors
  • Treatment Outcome
  • Warfarin / administration & dosage*
  • Warfarin / adverse effects


  • Anticoagulants
  • Warfarin