NOACs vs. Vitamin-K Antagonists for Stroke Prevention

Study Questions:

How does the safety and effectiveness of nonvitamin-K oral anticoagulants (NOACs) compare with vitamin-K antagonists (VKAs) in real-world, outside of clinical trial, practice?


This systematic review and meta-analysis identified observational studies comparing NOACs with VKAs for stroke prevention in patients with atrial fibrillation. The authors limited their search to national or health insurance claims databases to attempt to capture real-world data. The outcomes abstracted included ischemic stroke, ischemic stroke or systemic embolism, any stroke or systemic embolism, myocardial infarction, intracranial hemorrhage, major hemorrhage, gastrointestinal hemorrhage, and death. The study was performed according to MOOSE guidelines and risk of bias was assessed using GRADE principles.


There were 28 studies included in the analyses. Dabigatran was assessed in 24, VKAs in 23, rivaroxaban in 14, and apixaban in 7. There was no study assessing edoxaban. There was no significant bias identified in the included studies.

When dabigatran was compared with VKAs, there was no difference in the risk of ischemic stroke or systemic embolism (hazard ratio [HR], 1.17; 95% confidence interval [CI], 0.92-1.50) or myocardial infarction (HR, 0.96; 95% CI, 0.77-1.21). Dabigatran was associated with a lower risk of intracranial hemorrhage (HR, 0.42; 95% CI, 0.37-0.49) and death (HR, 0.63; 95% CI, 0.52-.076), but a higher risk of gastrointestinal bleeding (HR, 1.20; 95% CI, 1.06-1.36) than VKAs.

When rivaroxaban was compared with VKAs, there was no difference in the risk of ischemic stroke or systemic embolism (HR, 0.73; 95% CI, 0.52-1.04) or death (HR, 0.67; 95% CI, 0.35-1.30). The risk of gastrointestinal hemorrhage was higher with rivaroxaban when compared with VKAs (HR, 1.24; 95% CI, 1.08-1.41), but the risk of intracranial hemorrhage was lower (HR, 0.64; 95% CI, 0.47-0.86).

When apixaban was compared with VKAs, there was no difference in the risk of ischemic stroke or systemic embolism (HR, 1.07; 95% CI, 0.87-1.31). Apixaban was associated with a lower risk of intracranial hemorrhage (HR, 0.45; 95% CI, 0.31-0.63), gastrointestinal hemorrhage (HR, 0.63; 95% CI, 0.31-0.63), and death (HR, 0.65; 95% CI, 0.56-0.75) than VKAs.


These real-world data largely confirm the safety and effectiveness findings of the randomized controlled trials that compared NOACs with VKAs.


While randomized controlled trials represent the most rigorous way to evaluate a new drug, they are not always generalizable to the way the drug will be used in real-world clinical practice. There have been multiple studies comparing NOACs to VKAs and the present study synthesized this work in a meta-analysis. As a whole, when NOACs are compared with VKAs, they are associated with a similar risk of ischemic stroke and systemic embolism, and a lower risk of intracranial hemorrhage. While there are some individual differences among the NOACs, the conclusions from the present study support the findings from the randomized controlled trials, strengthening their validity.

Limitations of this study include its observational nature—the results could be confounded by issues related to patient characteristics, adherence to treatment, and prescribing indications. Additionally, different NOAC doses were not evaluated. However, the study is strengthened by the large sample size for many of the analyses and assessment of hard clinical outcomes.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Prevention, Anticoagulation Management and Atrial Fibrillation, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Anticoagulants, Antithrombins, Arrhythmias, Cardiac, Atrial Fibrillation, Embolism, Gastrointestinal Hemorrhage, Intracranial Hemorrhages, Myocardial Infarction, Primary Prevention, Risk Assessment, Stroke, Vascular Diseases, Vitamin K

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