Anusha Boyanpally, MD

Xue Z, Zhang H. Non–Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Asians With Atrial Fibrillation: Meta-Analysis of Randomized Trials and Real-World Studies. Stroke. 2019;50:2819–2828.

The authors have evaluated randomized control trials (RCT) and meta-analysis of observational studies (real-world studies) to compare the effects of non-vitamin K antagonist oral anticoagulation (NOACs) with warfarin in atrial fibrillation (AF) in the Asian population. The incidence of AF and complications associated with it are higher in the Asian population. Four worldwide RCT studies (1-4) compared NOACs with warfarin. NOACs demonstrated noninferiority in efficacy and reasonable safety. Specifically, in the Asian population, Wang et al. (5) have demonstrated that standard NOACs are safer and more effective in Asians. When a lower dose of NOACs was used in the Asian population, it still showed similar efficacy and safety. However, the Asian Pacific Heart Rhythm Society still recommends a standard dose of NOACs for the Asian population. Nevertheless, real-world efficacy and safety of NOACs in the Asian population is still unclear.

Five RCT trials and 21 observational studies were included in this analysis from January 2009 to February 2019. Efficacy endpoints are thromboembolic events such as stroke and systemic thromboembolism, ischemic stroke, myocardial injury, and all-cause death. Safety endpoints are major bleeding, intracranial bleeding, and gastrointestinal bleeding. Data abstraction and quality assessment were performed by 2 reviewers independently and used additional statistical tools to evaluate bias in the studies. RCT trials have a low risk of bias, whereas observational studies had a moderate-to-high quality with a Newcastle-Ottawa Scale score of ≥6 points.

In RCT trials, in the Asian population, standard dose NOACs had a lower risk of systemic embolisms, all-cause death, major bleeding, intracranial bleeding, and gastrointestinal bleeding when compared with warfarin. In the subgroup analysis, a lower dose of NOACs was associated with a lower risk of major bleeding and intracranial bleeding, but with comparable risk of efficacy outcomes when compared to warfarin. In observational (real-world) studies, NOACs are associated with reduced risk of stroke or systemic embolism, all-cause death, ischemic stroke, and myocardial infarction. As a safety indicator, it decreased gastrointestinal bleeding, major bleeding, and intracranial bleeding. These findings were not changed with type, dose of NOACs and age and follow-up time. Standard and low doses both can prevent stroke in the Asian population. Interestingly, a lower dose of NOACs had shown decreased rates of safety endpoints and comparable risks of efficacy endpoints in the Asian population. Also, NOACs in Asian cohorts decreased the incidence of myocardial infarction but did not explain the possible reasons. In elderly patients, the efficacy and safety of NOACs persisted when compared with warfarin.

In this fascinating study, the authors have conducted a meta-analysis in observational studies. The major drawback of the study is heterogenicity across the studies. Observational studies are retrospective in nature, which carries inherent limitations. There is no information regarding the nature of the AF, whether new or paroxysmal. Also, having a history of coronary artery disease, diabetes, and heart failure increases the risk of thromboembolism phenomenon. Incidence of stroke increases with the CHA2DS2-VASc score. Warfarin usually under-dosed many times, which might be reflecting NOACs as a better medication in some situations. Consistency of the INR range is not mentioned in these studies. Baseline characteristics (age, body weight, and comorbidities) and dietary habits are different in the Asian population compared to the non-Asian population, which might cause different pharmacokinetics for warfarin and NOACs. 

Despite these limitations, this is the first kind of meta-analysis of real-world study to assess the efficacy and safety of NOACs in the Asian population. Further research is required to explore the reasons and doses of these NOACs in the Asian population.


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