Direct oral anticoagulants for atrial fibrillation in patients with mitral stenosis

1. In this retrospective observational study, direct oral anticoagulant use for atrial fibrillation in patients with mitral stenosis was linked with decreased mortality and fewer thromboembolic events compared to warfarin. 

2. There was also a non-significant trend towards fewer episodes of intracranial hemorrhage with direct oral anticoagulant use.

Evidence Rating Level: 3 (Average)

Study Rundown: Atrial fibrillation is a common disease that greatly increases the risk of thromboembolic complications. Historically, warfarin was the mainstay oral anticoagulant used for reducing the risk of thromboembolism in these patients. More recently, direct oral anticoagulants (DOACs) have been shown to be at least as effective at reducing thromboembolism with lower risk of intracranial hemorrhage. However, patients with moderate to severe mitral stenosis as well as mechanical valve replacements have thus far been excluded from relevant trials.

This retrospective observational study in South Korea examined patients with atrial fibrillation and mitral stenosis treated with either a DOAC or warfarin. It found that DOAC use was linked with significantly lower systemic thromboembolism or ischemic stroke and significantly less all-cause mortality, with a non-significant trend towards less intracranial hemorrhage. There were several significant limitations. Firstly, severity of mitral stenosis was not available. The proportion of mild versus moderate to severe mitral stenosis patients could significantly impact results. Secondly, time in therapeutic INR was not provided, and so inappropriate warfarin dosing could be a potential confounder.

Click to read the study published in JACC

Relevant Reading: Edoxaban versus Warfarin in Patients with Atrial Fibrillation

In-Depth [retrospective cohort]: This was a retrospective observational study looking at 2,230 patients in South Korea with atrial fibrillation and mitral stenosis being treated with either a direct oral anticoagulant (DOAC) or warfarin. Inclusion criteria included at least three weeks of anticoagulant prescription between February 2008 and January 2017. Exclusion criteria included history of mitral valve surgery. Propensity score matching (for age, gender, diabetes, hypertension, stroke, congestive heart failure, vascular disease, dyslipidemia, chronic kidney disease, and chronic obstructive pulmonary disease) was performed 1:1 between patients on a DOAC versus those on warfarin. Primary outcome was first hospitalization with ischemic stroke or systemic embolism after three weeks of anticoagulant use. The safety endpoint was episode of intracranial hemorrhage. Of patients treated with a DOAC (n=1,115), 32.9% were on dabigatran, 42.3% were on rivaroxaban, 17.2% were on apixaban, and 7.5% were on edoxaban. Mean follow-up period was 27 months. There were significantly fewer strokes or systemic embolism in the DOAC group compared with warfarin (2.22%/year versus 4.19%/year, aHR 0.28, 95% CI 0.18 – 0.45, p < 0.0001). There was a non-significant trend towards less intracranial hemorrhage in the DOAC group (0.49%/year versus 0.93%/year, aHR 0.53, 95% CI 0.22 – 1.26, p=0.14). All-cause mortality was significantly lower in the DOAC group (3.45%/year versus 8.08%/year, aHR 0.41, 95% CI 0.30 – 0.56, p < 0.0001). A sensitivity analysis excluding patients above the 95^th percentile of risk or below the 5^th percentile of risk based on propensity score did not change results significantly.

Image: PD

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