Ilana Spokoyny, MD

Wang KL, Lip GYH, Lin SJ, and Chiang CE. Non–Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention in Asian Patients With Nonvalvular Atrial Fibrillation: Meta-Analysis. Stroke. 2015 

For Asian patients with atrial fibrillation, there has been hesitation to treating with Vitamin K antagonists due to increased rates of intracranial hemorrhage in Asians. NOACs may represent a safer alternative, but this has not been studied on a large scale in Asian patients until now. The authors performed a meta-analysis using data from recent clinical trials, to assess for differences in safety and efficacy of NOACs in Asian patients. Trials were included if they had more than 500 patients, followed for at least a year, and reported long term efficacy and safety in Asian patients. On literature review, 78 studies were identified but only 5 were included (RE-LY, ROCKET AF, J-ROCKET-AF, ARISTOTLE, ENGAGE AF-TIMI 48.) 8,928 Asian patients (5250 NOAC, 3678 VKA) and 64,033 Non-Asians (37800 NOAC, 26233 VKA) were included. The NOACs included were dabigatran, rivaroxaban, apixaban, and edoxaban. Two separate meta-analyses were performed to compare low- and high-dose NOACs to VKAs. 

One of the limitations addressed by the authors is that they could not determine the actual ethnicity of patients, just their country of residence. Three sensitivity analyses were performed to mitigate these factors, with largely the same results.

A common criticism of standard dose NOACs is their increased risk of GI bleeding – this was only shown to be significant in non-Asians.

So, what explains the differences between Asian and non-Asian patients? We still don’t know. There are likely multiple factors which affect a patient’s or group’s sensitivity to NOACs versus VKAs. The authors note that there may be different genetic polymorphisms in VKA metabolism accounting for higher hemorrhagic stroke in Asians treated with VKAs, with a lower rate by comparison in Asians treated with NOACs. Additional factors in Asians which may contribute to higher hemorrhagic stroke rates with VKAs include: lower body weight and lower creatinine clearance. Other variables identified in Asian patients which are less clearly linked are less prior VKA use (likely due to perception of higher risk of bleed), lower rates of prior MI, less common concomitant use of GI ppx, higher rates of renal impairment, higher rates of prior stroke and non-paroxysmal AFib, and more antiplatelet use.

Overall, the advent of NOACs was a game changer. They provide an easier-to-monitor alternative to Vitamin K Antagonists. This meta-analysis shows that standard dose NOACs are preferred in Asian patients, with regard to both safety and efficacy outcomes. Lower dose NOACs may be an effective and safe alternative in Asian patients with an especially high risk of bleeding, but do not have better efficacy than VKAs. This study can reassure providers in Asian countries (and probably providers in non-Asian countries treating Asian patients) that there are safe and efficacious drugs for stroke prevention in atrial fibrillation. It is likely that many Asian patients are placed on antiplatelets in lieu of VKAs, due to perceived risk of intracerebral bleed. These patients will benefit from anticoagulation, and now have a good alternative to VKAs.