Major bleeding risk higher for dabigatran than for warfarin, study suggests

Research suggests that dabigatran is associated with a higher risk of bleeding compared with warfarin in a US population sample.

Veltassa, a polymer that binds to potassium in the gastrointestinal tract treating potentially fatal levels in patients with chronic kidney disease (micrograph pictured)

The oral anticoagulant dabigatran is associated with a higher incidence of major bleeding compared with warfarin, especially for black patients and those with chronic kidney disease, according to the authors of a new study published in JAMA Internal Medicine

For clinicians managing patients at risk of blood clots, the newer oral anticoagulants were a welcome addition to available treatment options because they do not require the intense monitoring needed for warfarin therapy. However, studies examining the risk of bleeding associated with these newer agents are inconclusive. 

Compared with warfarin, dabigatran was associated with a higher risk of bleeding (hazard ratio 1.30, 95% confidence interval 1.20–1.41), major bleeding (HR 1.58, 95% CI 1.36–1.83) and gastrointestinal bleeding (HR 1.85, 95% CI 1.64–2.07). But dabigatran was associated with a lower risk of intracranial haemorrhage (HR 0.32, 95% CI 0.20–0.50).

“Dabigatran should be prescribed with caution in high-risk patients,” the researchers conclude. 

But lead cardiac pharmacist Paul Wright, from the Heart Hospital, a specialist cardiac hospital in London, says the results should be interpreted with caution owing to the relatively small size of the study. The retrospective cohort analysis used data from the US Medicare health programme which included 1,302 patients receiving dabigatran and 8,102 patients receiving warfarin[2]

Dabigatran was first granted a marketing authorisation in the European Union in 2008 and is licensed for the prevention of blood clots in patients who have undergone elective hip or knee replacement surgery and for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation, as well as the treatment and prevention of deep vein thrombosis and pulmonary embolism. 

Wright highlights previous trials comparing dabigatran and warfarin that included many more patients than the current trial. A randomised controlled trial known as RELY enrolled around 18,000 patients and another recent retrospective cohort analysis included 134,414 patients[3]
. “Evidence from these trials indicates that dabigatran is associated with an increased risk of gastrointestinal bleeding, a reduced risk of intracranial haemorrhage and a similar overall risk of bleeding compared with warfarin,” says Wright. At the moment, these conclusions have the most supporting evidence, he says. 

In addition, Wright points out that high-risk elderly patients (over 75 years of age) and those with chronic kidney disease should be given a lower dose of dabigatran but that the report in JAMA Internal Medicine does not make it clear whether this recommendation was followed. He also believes that conclusions regarding risk of bleeding in black patients are not based on a large enough cohort to be reliable. 



[1] Hernandez I, Baik SH, Pinera A et al. Risk of bleeding with dabigatran in atrial fibrillation. JAMA Internal Medicine. 2014 doi:10.1001/jamainternmed.2014.5398 (accessed 4 November 2014).

[2] Graham DJ, Reichman ME, Wernecke M et al. Cardiovascular, Bleeding, and Mortality Risks in Elderly Medicare Patients Treated with Dabigatran or Warfarin for Non-Valvular Atrial Fibrillation. Circulation. 2014. doi: 10.1161/CIRCULATIONAHA.114.012061.

[3] Connolly SJ, Ezekowitz MD, Yusuf S et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2009; 361:1139–1151.

Last updated
The Pharmaceutical Journal, PJ, 22/29 November 2014, Vol 293, No 7837/8;293(7837/8)::DOI:10.1211/PJ.2014.20067152

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