# Effectiveness of direct oral anticoagulants for all‐cause mortality and cardiovascular events in overweight and obese patients with atrial fibrillation: Insight from the nationwide START registry

## TL;DR

DOACs may be better than VKAs for reducing mortality and cardiovascular events in overweight and obese atrial fibrillation patients.

## Contribution

This study provides real-world evidence on DOACs' effectiveness in overweight and obese AF patients using a nationwide registry.

## Key findings

- DOACs were linked to lower all-cause mortality and cardiovascular events compared to VKAs.
- Mortality benefits of DOACs were consistent in both overweight and obese patients.
- Cardiovascular event reduction was significant only in overweight patients.

## Abstract

Overweight and obesity are highly prevalent in atrial fibrillation (AF) patients, yet the best anticoagulant strategy for this group is still unclear. We evaluated the risk of all‐cause mortality and cardiovascular events (CVEs) in overweight and obese AF patients treated with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs).

We analysed 10,259 AF patients on anticoagulants from the prospective nationwide START registry. Overweight was defined as BMI 25–29.9 kg/m2 and obesity as BMI ≥30 kg/m2. Mortality risk was assessed with Cox proportional hazards models, and CVEs with Fine–Grey models accounting for competing risks. Additional modelling strategies, subgroup analyses, and propensity score matching were performed to explore data and ensure robustness.

Overall, 6534 (63.7%) patients had BMI >25 kg/m2 (65.7% overweight, 34.3% obese). Over a median follow‐up of 17.4 months, 408 deaths and 481 CVEs occurred. DOACs' use was associated with a lower risk of all‐cause mortality (HR 0.57, 95% CI 0.46–0.70, p < 0.001) and CVEs (sHR 0.71, 95% CI 0.59–0.86, p < 0.001) versus VKAs. The inverse association of DOACs with mortality was evident in both overweight (HR 0.52, 95% CI 0.39–0.68, p < 0.001) and obese patients (HR 0.69, 95% CI 0.48–0.98, p = 0.040), while the reduction in CVEs reached significance only in the overweight group.

In this nationwide registry, DOACs were associated with lower risks of mortality and CVEs compared with VKAs across BMI groups, though the CVE effect was not evident in obese patients. These findings suggest a potential mortality advantage of DOACs irrespective of BMI, warranting further confirmation.

This study shows that overweight and obese patients with atrial fibrillation experience improved outcomes when treated with DOACs compared with VKAs. Specifically, DOAC use was associated with lower risks of all‐cause mortality and cardiovascular events. The mortality benefit was consistent across both overweight and obese groups, while the reduction in cardiovascular events was more evident in overweight patients. These findings suggest a mortality advantage of DOACs irrespective of BMI and support their preferential use in this population.