Effectiveness and safety of 110 or 150 mg dabigatran vs. vitamin K antagonists in nonvalvular atrial fibrillation

Br J Clin Pharmacol. 2019 Feb;85(2):432-441. doi: 10.1111/bcp.13815. Epub 2018 Dec 16.

Abstract

Aims: We compared the 1-year safety and effectiveness of dabigatran 110 mg (D110) or 150 mg (D150) twice daily to vitamin K antagonists (VKA) in patients with nonvalvular atrial fibrillation.

Methods: New user cohort study of patients dispensed D110 or D150 vs. VKA in 2013 for nonvalvular atrial fibrillation, followed 1 year in the French Système National des Données de Santé (66 million persons). D110 and D150 users were matched 1:1 with VKA users on sex, age, date of first drug dispensing and high-dimensional propensity score. Hazard ratios [HR (95% confidence intervals)] for stroke and systemic embolism (SSE), major bleeding (MB) and death were computed using Cox proportional hazards or Fine and Gray models during exposure.

Results: In 14 442 matched D110 and VKA patients, mean age 79, 49% male, 91% with CHA2 DS2 -VASc ≥2 and 8% with HAS-BLED score >3, incidence rates of SSE were 1.9% and 2.6% person-years [HR 0.69 (0.56-0.84)], MB 1.8% and 2.9% [0.62 (0.51-0.76)], death 7.2% and 8.6% [0.84 (0.76-0.94)]. In 8389 matched D150 and VKA patients, mean age 67, 67% male, 65% with CHA2 DS2 -VASC ≥2; < 5% HAS-BLED >3, incidence rates were for SSE 1.4% and 1.9% [0.76 (0.56-1.04)], MB 0.6% and 1.9% [0.30 (0.20-0.46)], death 1.6% and 3.6% [0.46 (0.35-0.59)]. Numbers needed to treat to observe one fewer death were 78 for D110, 88 for D150.

Conclusion: In real life D110 and D150 were at least as effective, and safer than VKA.

Keywords: comparative effectiveness; dabigatran; dose-effect; pharmacoepidemiology; vitamin K antagonists.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Atrial Fibrillation / complications
  • Atrial Fibrillation / drug therapy*
  • Dabigatran / administration & dosage*
  • Dabigatran / adverse effects
  • Dose-Response Relationship, Drug
  • Embolism / epidemiology
  • Embolism / etiology
  • Embolism / prevention & control
  • Female
  • Follow-Up Studies
  • France / epidemiology
  • Hemorrhage / chemically induced
  • Hemorrhage / epidemiology
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Prospective Studies
  • Stroke / epidemiology
  • Stroke / etiology
  • Stroke / prevention & control
  • Treatment Outcome
  • Vitamin K / antagonists & inhibitors*

Substances

  • Anticoagulants
  • Vitamin K
  • Dabigatran