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

J Am Coll Cardiol. 2018 Jul 17;72(3):255-267. doi: 10.1016/j.jacc.2018.04.063. Epub 2018 Jul 9.

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).

Keywords: NSAID; anticoagulation; atrial fibrillation; bleeding; stroke prevention.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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

Associated data

  • ClinicalTrials.gov/NCT00262600