Concomitant NSAID use in patients with atrial fibrillation was associated with an increased risk of major bleeding (HR 1.68; 95% CI 1.40-2.02; p<0.0001) and stroke or systemic embolism.
RCT (n=18,113)
Does NSAID use increase the risk of adverse clinical outcomes in patients with atrial fibrillation receiving oral anticoagulants?
In patients with atrial fibrillation on oral anticoagulants, concomitant NSAID use is associated with significantly increased risks of major bleeding, stroke/systemic embolism, and hospitalization.
Effect estimate: HR 1.68 (95% CI 1.40 to 2.02)
p-value: p=< 0.0001
BACKGROUND Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used medications that can potentially increase the risk of bleeding and thrombosis. OBJECTIVES This study quantified the effect of NSAIDs in the RE-LY (Randomized Evaluation of Long Term Anticoagulant Therapy) trial. METHODS This was a post hoc analysis of NSAIDs in the RE-LY study, which compared dabigatran etexilate (DE) 150 and 110 mg twice daily (b.i.d.) with warfarin in patients with atrial fibrillation. Treatment-independent, multivariate-adjusted Cox regression analysis assessed clinical outcomes by comparing NSAID use with no NSAID use. Interaction analysis was obtained from treatment-dependent Cox regression modeling. Time-varying covariate analysis for NSAID use was applied to the Cox model. RESULTS Among 18,113 patients in the RE-LY study, 2,279 patients used NSAIDs at least once during the trial. Major bleeding was significantly elevated with NSAID use (hazard ratio HR: 1.68; 95% confidence interval CI: 1.40 to 2.02; p < 0.0001). NSAID use did not significantly alter the risk of major bleeding for DE 150 or 110 mg b.i.d. relative to warfarin (pinteraction = 0.63 and 0.93, respectively). Gastrointestinal major bleeding was significantly elevated with NSAID use (HR: 1.81; 95% CI: 1.35 to 2.43; p < 0.0001). The rate of stroke or systemic embolism (stroke/SE) with NSAID use was significantly elevated (HR: 1.50; 95% CI: 1.12 to 2.01; p = 0.007). The use of NSAIDs did not significantly alter the relative efficacy on stroke/SE for DE 150 or 110 mg b.i.d. relative to warfarin (pinteraction = 0.59 and 0.54, respectively). Myocardial infarction rates were similar with NSAID use compared with no NSAID use (HR: 1.22; 95% CI: 0.77 to 1.93; p = 0.40). Patients were more frequently hospitalized if they used an NSAID (HR: 1.64; 95% CI: 1.51 to 1.77; p < 0.0001). CONCLUSIONS The use of NSAIDs was associated with increased risk of major bleeding, stroke/SE, and hospitalization. The safety and efficacy of DE 150 and 110 mg b.i.d. relative to warfarin were not altered. (Randomized Evaluation of Long Term Anticoagulant Therapy RE-LY; NCT00262600).
Kent et al. (2018) conducted an RCT in Atrial fibrillation (n=18,113). NSAIDs vs. No NSAID use was evaluated on Major bleeding (HR 1.68, 95% CI 1.40 to 2.02, p=< 0.0001). Concomitant NSAID use in patients with atrial fibrillation was associated with an increased risk of major bleeding (HR 1.68; 95% CI 1.40-2.02; p<0.0001) and stroke or systemic embolism.