Concomitant Oral Anticoagulant and Nonsteroidal Anti-Inflammatory Drug Therapy in Patients With Atrial Fibrillation.

Abstract

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).

• Authors: Anthony P Kent, Martina Brueckmann, Mandy Fraessdorf, Stuart J Connolly, Salim Yusuf, John W Eikelboom, Jonas Oldgren, Paul A Reilly, Lars Wallentin, Michael D Ezekowitz
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 72 Issue 3 Pg. 255-267 (07 17 2018) ISSN: 1558-3597 [Electronic] United States
• PMID: 30012318 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018. Published by Elsevier Inc.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Warfarin
• Dabigatran

Topics

• Aged
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, adverse effects)
• Atrial Fibrillation (complications, drug therapy)
• Dabigatran (administration & dosage, adverse effects)
• Drug Interactions
• Drug Therapy, Combination (adverse effects, methods)
• Female
• Gastrointestinal Hemorrhage (chemically induced, diagnosis)
• Hospitalization (statistics & numerical data)
• Humans
• Male
• Middle Aged
• Outcome and Process Assessment, Health Care
• Stroke (etiology, prevention & control)
• Thromboembolism (etiology, prevention & control)
• Warfarin (administration & dosage, adverse effects)