Clinical Question

In a real-world setting, how do the harms of dabigatran (Pradaxa) and warfarin (Coumadin) compare?

Bottom Line

In this well-designed observational study, older patients given an initial prescription of dabigatran had lower all-cause mortality (number needed to treat [NNT] = 192 for one year) and fewer ischemic and hemorrhagic strokes, but a higher risk of gastrointestinal (GI) bleeding, than a matched group of patients given warfarin. Benefits and harms were greater at the higher dose (150 mg) and varied by age and sex. Specifically, women 85 years and older had higher all-cause mortality with dabigatran. (Level of Evidence = 2b)

Synopsis

The comparative safety of the novel oral anticoagulants is important knowledge, because they are being widely adopted at great cost to the health system. Although they are clearly more convenient than warfarin, are they also safer? This study identified Medicare patients 65 years and older who were given an initial prescription for warfarin or dabigatran for the treatment of nonvalvular atrial fibrillation. It is important to include only new users, because the first few months are when patients are at the highest risk of bleeding complications. Each dabigatran user was matched to a warfarin user via propensity score matching, which matches patients based on factors associated with the likelihood of being prescribed dabigatran, using logistic regression. The result was two groups that looked very similar: 59% were 75 years and older, 51% were women, 92% were white, 33% had diabetes mellitus, and approximately 50% had ischemic heart disease. Their CHADS₂ score, a measure of stroke risk, was 2 or higher for 71%, and the HAS-BLED score, a measure of bleeding risk, was 2 or 3 for 82%. Ultimately, there were 67,207 patients in each group; slightly more than one-half in each group filled only a single prescription for their anticoagulant, and there were slightly more than 19,000 person-years of follow-up in each group. Thus, the outcomes largely reflect harms accrued soon after beginning each medication.

There were several important differences between groups. Patients given dabigatran had significantly fewer ischemic strokes (11.3 vs. 13.9 per 1,000 person-years; NNT = 607 per year), fewer intracranial hemorrhages (3.3 vs. 9.6 per 1,000 person-years; NNT = 158 per year), and lower all-cause mortality (32.6 vs. 37.8 per 1,000 person-years; NNT = 192 per year). However, they had a significantly higher risk of major GI bleeding (34.2 vs. 26.5 per 1,000 person-years; number needed to treat to harm = 129 per year). The increased GI bleeding risk was primarily in women 75 years and older and in men 85 years and older. All of the benefits and harms were greater with a dabigatran dosage of 150 mg twice daily, and were statistically significant only for the reduction in the risk of intracranial hemorrhage at the 75-mg dose.

Study design: Cohort (retrospective)

Funding source: Government

Setting: Population-based

Reference: GrahamDJReichmanMEWerneckeMet alCardiovascular, bleeding, and mortality risks in elderly Medicare patients treated with dabigatran or warfarin for nonvalvular atrial fibrillation. Circulation2015; 131( 2): 157– 164.