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Hemorrhagic stroke rates are higher with warfarin in Asians vs. non-Asians with atrial fibrillation (A-fib), but dabigatran appears to reduce those rates in all patients regardless of ethnic background, according to results published online June 6, 2013, ahead of print in Stroke.

Researchers led by Masatsugu Hori, MD, PhD, of the Osaka Medical Center for Cancer and Cardiovascular Diseases (Osaka, Japan), evaluated stroke data from the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, which compared the use of 2 fixed doses of dabigatran (110 mg and 150 mg twice a day), with warfarin in A-fib patients from 10 Asian countries (n = 2,782) and 34 non-Asian countries (n = 15,331).

Compared with warfarin, the rate of stroke or systemic embolism was significantly lower in both Asian and non-Asian patients with the higher dose of dabigatran (table 1).

Table 1. Yearly Stroke or System Embolism: Dabigatran vs. Warfarin

There were no treatment-by-region interactions for either dose of dabigatran on outcome measures including stroke, ischemic stroke, hemorrhagic stroke, MI, or death from any cause. Rates of ischemic stroke were doubled in Asian vs. non-Asian patients taking warfarin (2.02% vs. 0.98% per year).

On warfarin, the rate of major bleeding in Asian patients was 3.82% per year, compared with 2.22% and 2.17% per year, respectively, for the 110- and 150-mg doses of dabigatran. In non-Asians, the rates were 3.53%, 2.99%, and 3.52% per year, respectively. There was a significant interaction between treatment and region for the 150-mg dose of dabigatran compared with warfarin in Asians vs. non-Asians (P = 0.008).

Hemorrhagic stroke occurred at a rate of 0.75% per year in Asian patients with warfarin, compared to 0.32% per year with warfarin in non-Asian patients (HR 2.4; 95% CI 1.3-4.7; P = 0.007). Conversely, with dabigatran 150 mg, Asian patients had a hemorrhagic stroke rate of only 0.17% per year and non-Asians had a rate of 0.09% per year.

Improving on Warfarin

In an e-mail communication with TCTMD, Dr. Mori noted that the findings of the subgroup analysis are consistent with the overall results from the RE-LY trial. Although previous reports have indicated that the benefits of dabigatran vs. warfarin may be attenuated in older patients compared with younger patients, the effect on major bleeding in the current analysis did diminish when adjusted for age (P = 0.06). However, total bleeding rates still showed highly significant improvements with both dabigatran doses after age adjustment.

Philip M. Meyers, MD, of Columbia University Medical Center (New York, NY), told TCTMD in a telephone interview that while the analysis is interesting, additional supporting evidence is needed.

“It has been recognized that Asians are at greater risk for hemorrhaging on warfarin, and it’s kind of interesting to see that there is now a drug that they seem to respond to,” he said. “I think it’s an important data point. I don’t know if this is going to be a paradigm shift.”

Among the study’s limitations are the small number of Asian patients compared with non-Asians, as well as demographic differences between the groups.

Still, Dr. Mori said that the analysis “provides strong support” that dabigatran is safe and effective for all patients with A-fib.

Source:

Hori M, Connolly SJ, Zhu J, et al. Dabigatran versus warfarin: Effects on ischemic and hemorrhagic strokes and bleeding in Asians and non-Asians with atrial fibrillation. Stroke. 2013;Epub ahead of print.

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