Claude Nguyen, MD
Zhu J, Li
Dabigatran Versus Warfarin: Effects on Ischemic and Hemorrhagic Strokes and Bleeding in Asians and Non-Asians With Atrial Fibrillation. Stroke. 2013
For Asians with atrial fibrillation, dabigatran may be safer than warfarin.The RE-LY trial provided evidence that dabigatran is superior to warfarin in the secondary prevention of stroke in those with atrial fibrillation, with similar rates of hemorrhagic complications at the 150mg BID dose. Despite this promise, however, it may be years before we understand the true pharmacogenomics of any new medication. Hori et al., sponsored by Boehringer Ingelheim, represented a consortium of Asian and Southeast Asian countries in addition to the US and Canada, which studied the bleeding rates of Asians versus non-Asians as a subgroup analysis of the RE-LY trial. They were motivated by prior evidence that Asians taking warfarin are at higher risk of developing hemorrhage.
Asians in the RE-LY trial were compared to non-Asians in terms of the 3 treatment groups in the trial (dabigatran 110mg BID vs. 150mg BID vs. warfarin). Asians were younger, had lower body weight, and higher rate of prior stroke, while non-Asians had higher proportion of previous MI. The group also performed a geographic analysis of the data, finding that it correlated with stroke and bleeding rates by ethnic origin. In both Asians and non-Asians, rates of stroke or systemic embolism was lower with the higher dabigatran dose compared to warfarin. There was no evidence of a treatment effect by region. Given that Asians were younger than non-Asians in the study, there was a greater benefit for dabigatran amongst Asians, which was attenuated after age adjustment.
The group found that Asians treated with warfarin had higher incidences of bleeding, despite being younger and having lower therapeutic INR ranges than non-Asians. They also found that bleeding rates were significantly lower with dabigatran compared to warfarin amongst the Asian group; however, an interaction between treatment and region was found. Major bleeding was higher in Asians, thought to be not only due to genetic factors, but to a higher proportion of previous stroke compared to non-Asians.
As with any subgroup analysis, this study is not without limitations, particularly as the proportion of Asians was small compared to the non-Asian group. Even though there are similarities between Asian subgroups, it is important to note that Asians are a heterogeneous group, as evidenced by the regional differences between Asians in the study and its effect on treatment. Therefore, these results may not necessarily be applicable to Americans with Asian heritage. Nevertheless, this is the best evidence we have that dabigatran may be a safer alternative than warfarin in Asians with atrial fibrillation. Before we accept these findings, however, they must be replicated in other studies.