No evidence for higher bleeding incidence in real world dabigatran-treated patients

Efficacy and safety of dabigatran etexilate and warfarin in ‘real world’ patients with atrial fibrillation: A prospective nationwide cohort study.

Literature - Larsen TB, Rasmussen LH, Skjoth F et al., - J Am Coll Cardiol. 2013

Larsen TB, Rasmussen LH, Skjoth F et al.,
J Am Coll Cardiol. 2013


Stroke is a serious complication of atrium fibrillation (AF), which can be prevented with oral anticoagulation (OAC). Until recently vitamin K antagonists (VKA) were used, such as warfarin. VKA have the disadvantage that they need regular monitoring and that they may interact with food and drugs.
Dabigatran etexilate is a new oral direct thrombin inhibitor. Since August 2011 it has been available in Denmark in two doses (150 and 110 mg BID) for stroke prevention in AF in patients with one or more risk factors, based on results obtained in the RE-LY (Randomised evaluation of long-term anticoagulant therapy) phase 3 trial. RE-LY showed that dabigatran 110 mg BID was non-inferior to warfarin for the primary endpoint of stroke and systemic embolism, with 20% less major bleeding events, while 150 mg BID showed superiority for the primary efficacy endpoint, with a similar bleeding rate to warfarin [2]. Some concerns existed about a numerical (but not statistically significant) increase in myocardial infarction and bleeding events among dagibatran-treated patients both during RE-LY and after the introduction of dabigatran [3-6].
This nationwide cohort study aims to assess the efficacy and safety dabigatran etexilate as compared to warfarin in an ‘everyday clinical practice’ population of patients with AF.

Main results

  • The primary study outcome of stroke and systemic embolism did not differ between the warfarin and dabigatran group.
  • Mortality was significantly lower in de group treated with dabigatran 110 mg BID (adjusted HR (aHR): 0.79, 95%CI: 0.65-0.96), or with dabigatran 150 mg BID (aHR: 0.57, 95%CI: 0.40-0.80), as compared to patients receiving warfarin.
  • Major bleeding event rate did not differ between warfarin and dabigatran (both doses). Incidence of intracranial bleeding was lower at both dabigatran doses vs warfarin: 110 mg BID: aHR: 0.24, 95%CI: 0.08-0.56) and 150 mg BID: aHR: 0.08 (95%CI: 0.01-0.40).
  • The incidence of myocardial infarction, pulmonary embolism and all-cause hospitalisation was lower in both dabigatran doses as compared to warfarin.


This first report on a large ’everyday clinical practice’ post-approval clinical cohort showed  a similar efficacy in terms of prevention of stroke and systemic embolism among patients treated with dabigatran and propensity-matched patients treated with warfarin. Although this cohort was at lower risk than the patients in the RE-LY study, even after adjustment for risk factors and propensity scores it reassures that dabigatran does not cause an increase of myocardial infarction or bleeding events. These results do not underscore previous concerns about an excess of bleeding events amongst dabigatran-treated patients.


1. Banerjee A, Marín F, Lip GYH. A new landscape for stroke prevention in atrial fibrillation: focus on new anticoagulants, antiarrhythmic drugs, and devices. Stroke; a journal of cerebral circulation. 2011; 42:3316–22
2. Connolly SJ, Ezekowitz MD, Yusuf S et al. for the R-LSC and I. Dabigatran versus warfarin in patients with atrial fibrillation. The New England journal of medicine. 2009; 361:1139–51.
3. Hohnloser SH, Oldgren J, Yang S, et al. Myocardial ischemic events in patients with atrial fibrillation treated with dabigatran or warfarin in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial. Circulation. 2012; 125:669–76.
4. Truumees E, Gaudu T, Dieterichs C, et al. Epidural hematoma and intraoperative hemorrhage in a spine trauma patient on Pradaxa (dabigatran). Spine. 2012; 37:E863–5.
5. Legrand M, Mateo J, Aribaud A. The use of dabigatran in elderly patients. Archives of internal medicine. 2011; 171:1285–6.
6. Wychowski MK, Kouides PA. Dabigatran-induced gastrointestinal bleeding in an elderly patient with moderate renal impairment. The Annals of pharmacotherapy. 2012; 46:e10.

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