Selective Serotonin Reuptake Inhibitors and Bleeding Risk in Anticoagulated Patients With Atrial Fibrillation: An Analysis From the ROCKET AF Trial

J Am Heart Assoc. 2018 Aug 7;7(15):e008755. doi: 10.1161/JAHA.118.008755.

Abstract

Background There is concern that selective serotonin reuptake inhibitors ( SSRI s) substantially increase bleeding risk in patients taking anticoagulants. Methods and Results We studied 737 patients taking SSRI s in the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Embolism and Stroke Trial in Atrial Fibrillation) trial of rivaroxaban compared with warfarin for the prevention of stroke/systemic embolism in patients with atrial fibrillation. These patients were propensity score matched 1:1 to 737 patients not taking SSRI s. The primary outcome measure was major and nonmajor clinically relevant bleeding events, the principal safety outcome in ROCKET AF . Over a mean 1.6 years of follow-up, the rate of major/ nonmajor clinically relevant bleeding was 18.57 events/100 patient-years for SSRI users versus 16.84 events/100 patient-years for matched comparators, adjusted hazard ratio ( aHR ) of 1.16 (95% confidence interval [CI], 0.95-1.43). The aHR s were similar in patients taking rivaroxaban ( aHR 1.11 [95% CI, 0.82-1.51]) and those taking warfarin ( aHR 1.21 [95% CI, 0.91-1.60]). For the rarer outcome of major bleeding, the aHR for SSRI users versus those not taking SSRI s was 1.13 (95% CI, 0.62-2.06) for rivaroxaban; for warfarin, the aHR was higher, at 1.58 (95% CI , 0.96-2.60) but not statistically significantly elevated. Conclusions We found no significant increase in bleeding risk when SSRI s were combined with anticoagulant therapy, although there was a suggestion of increased bleeding risk with SSRI s added to warfarin. While physicians should be vigilant regarding bleeding risk, our results provide reassurance that SSRI s can be safely added to anticoagulants in patients with atrial fibrillation . Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT 00403767.

Trial registration: ClinicalTrials.gov NCT00403767.

Keywords: anticoagulation; atrial fibrillation; bleeding risk; rivaroxaban; selective serotonin reuptake inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anticoagulants / therapeutic use*
  • Anxiety Disorders / drug therapy
  • Atrial Fibrillation / complications
  • Atrial Fibrillation / drug therapy*
  • Depressive Disorder / drug therapy
  • Embolism / etiology
  • Embolism / prevention & control
  • Female
  • Hemorrhage / chemically induced*
  • Hemorrhage / epidemiology
  • Humans
  • Male
  • Proportional Hazards Models
  • Risk Factors
  • Rivaroxaban / therapeutic use
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Stroke / etiology
  • Stroke / prevention & control*
  • Warfarin / therapeutic use

Substances

  • Anticoagulants
  • Serotonin Uptake Inhibitors
  • Warfarin
  • Rivaroxaban

Associated data

  • ClinicalTrials.gov/NCT00403767