Direct Oral Anticoagulant- or Warfarin-Related Major Bleeding: Characteristics, Reversal Strategies, and Outcomes From a Multicenter Observational Study

Chest. 2017 Jul;152(1):81-91. doi: 10.1016/j.chest.2017.02.009. Epub 2017 Feb 17.

Abstract

Background: Direct oral anticoagulants (DOACs) have expanded the armamentarium for antithrombotic therapy. Although DOAC-related major bleeding was associated with favorable outcomes compared with warfarin in clinical trials, warfarin effects were reversed in < 40% of cases, raising concerns about the generalizability of this finding.

Methods: Consecutive patients ≥ 66 years presented to five tertiary care hospitals across three cities in Ontario, Canada from October 2010 to March 2015 with diagnoses that included hemorrhage. Charts were screened for association with DOAC or warfarin use; eligible cases were abstracted and linked to administrative databases.

Results: Among 19,061 records screened, 2,002 (460 receiving DOAC, 1,542 receiving warfarin) were eligible. Reversal agents (72.9% vitamin K, 40.7% prothrombin complex concentrates) were frequently used in warfarin bleeding events. Red blood cell transfusions occurred more often in DOAC bleeding events than in warfarin events (52.0% vs 39.5%; adjusted relative risk [aRR], 1.32; 95% CI, 1.19-2.47). However, units of blood products transfused were not different between the two groups. Thirty-four DOAC cases (7.4%) received activated prothrombin complex concentrates or recombinant factor VIIa. In-hospital mortality was lower following DOAC bleeding events (9.8% vs 15.2%; aRR, 0.66; 95% CI, 0.49-0.89), although differences in 30-day mortality did not reach statistical significance (12.6% vs 16.3%; aRR, 0.79; 95% CI, 0.61-1.03).

Conclusions: In this unselected cohort of patients with oral anticoagulant-related hemorrhage with high rates of warfarin reversal, in-hospital mortality was lower among DOAC-associated bleeding events. These findings support the safety of DOACs in routine care and present useful baseline measures for evaluations of DOAC-specific reversal agents.

Keywords: atrial fibrillation; major bleeding; oral anticoagulants; postmarketing drug safety.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects
  • Antithrombins / administration & dosage
  • Antithrombins / adverse effects
  • Atrial Fibrillation / complications
  • Blood Coagulation Factors / therapeutic use*
  • Dabigatran* / administration & dosage
  • Dabigatran* / adverse effects
  • Erythrocyte Transfusion* / methods
  • Erythrocyte Transfusion* / statistics & numerical data
  • Factor VIIa / therapeutic use*
  • Female
  • Hemorrhage* / chemically induced
  • Hemorrhage* / diagnosis
  • Hemorrhage* / mortality
  • Hemorrhage* / therapy
  • Hospital Mortality
  • Humans
  • Male
  • Medication Therapy Management / statistics & numerical data
  • Ontario / epidemiology
  • Recombinant Proteins / therapeutic use
  • Retrospective Studies
  • Stroke / etiology
  • Stroke / prevention & control*
  • Warfarin* / administration & dosage
  • Warfarin* / adverse effects

Substances

  • Anticoagulants
  • Antithrombins
  • Blood Coagulation Factors
  • Recombinant Proteins
  • prothrombin complex concentrates
  • Warfarin
  • recombinant FVIIa
  • Factor VIIa
  • Dabigatran

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