NSAID use ups risk of major bleeding, stroke in patients with atrial fibrillation
Nonsteroidal anti-inflammatory drugs (NSAIDs) appear to increase the risk of major bleeding, stroke or systemic embolism, and hospitalization among patients with atrial fibrillation (AF), suggest the results of the RE-LY* trial. Moreover, there is no difference in the safety and efficacy of dabigatran etexilate (DE) 150 and 110 mg twice daily relative to warfarin.
A total of 18,113 patients were included in the RE-LY study, of which 2,279 used NSAIDs at least once during the trial. NSAID users had significantly elevated major bleeding (hazard ratio [HR], 1.68; 95 percent CI, 1.40–2.02; p<0.0001). NSAID vs warfarin use did not significantly alter the risk of major bleeding for DE 150 or 110 mg twice daily (p=0.63 and p=0.93 for interaction, respectively).
NSAID use significantly elevated gastrointestinal major bleeding (HR, 1.81; 1.35–2.43; p<0.0001) and the rate of stroke or systemic embolism (HR, 1.50; 1.12–2.01; p=0.007), but it did not significantly alter the relative efficacy on stroke or systemic embolism for DE 150 or 110 mg twice daily relative to warfarin (p=0.59 and p=0.54 for interaction, respectively).
Rates of myocardial infarction were comparable between NSAID use and no NSAID use (HR, 1.22; 0.77–1.93; p=0.40). Furthermore, NSAID use resulted in frequently more hospitalizations (HR, 1.64; 1.51–1.77; p<0.0001).
The authors performed a posthoc analysis of NSAIDs in the RE-LY trial, which compared DE 150 and 110 mg twice daily with warfarin in patients with AF. Clinical outcomes were assessed using treatment-independent, multivariate-adjusted Cox regression analysis by comparing NSAID use with no NSAID use. Interaction analysis was obtained from treatment-dependent Cox regression modelling, and time-varying covariate analysis for NSAID use was applied to the Cox model.
*Randomized Evaluation of Long Term Anticoagulant Therapy