The concurrent use of antithrombotic therapies and the risk of bleeding in patients with atrial fibrillation

Laurent Azoulay; Sophie Dell’Aniello; Teresa Simon; Christel Renoux; Samy Suissa

doi:10.1160/TH12-08-0542

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2013; 109(03): 431-439
DOI: 10.1160/TH12-08-0542

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

The concurrent use of antithrombotic therapies and the risk of bleeding in patients with atrial fibrillation

Laurent Azoulay

¹Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada

²Department of Oncology, McGill University, Montreal, Quebec, Canada

,

Sophie Dell’Aniello

¹Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada

,

Teresa Simon

³Bristol–Myers Squibb, Lawrenceville, New Jersey, USA

,

Christel Renoux

¹Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada

⁴Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada

,

Samy Suissa

¹Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada

⁵Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada

› Author Affiliations

Abstract

Summary

Patients with atrial fibrillation (AF) often receive, in addition to warfarin, antithrombotic drugs to manage other comorbid conditions. To date, few population-based studies have quantified the bleeding risk associated with the concurrent use of these therapies. The United Kingdom General Practice Research Database was used to identify a cohort of 70,760 patients newly-diagnosed with AF between 1993 and 2008. A nested case-control analysis was conducted within that cohort, and conditional logistic regression was used to estimate adjusted rate ratios (RRs) of bleeding associated with current use of warfarin, aspirin, and clopidogrel in single therapy, as well as in dual and triple therapy, as compared with non-use of any therapy. A total of 10,850 patients experienced a bleeding event during follow-up. In single therapy, warfarin was associated with the highest increased risk (RR: 2.08, 95% confidence interval [CI]: 1.95–2.23), followed by clopidogrel (RR: 1.57, 95% CI: 1.37–1.81) and aspirin (RR: 1.25, 95% CI: 1.17–1.34). In dual therapy, combinations containing warfarin were associated with a higher increased risk (warfarin-aspirin: RR: 2.87, 95% CI: 2.58–3.19, and warfarin-clopidogrel: RR: 2.74, 95% CI: 2.14–3.51), than those not containing warfarin (aspirin-clopidogrel: RR: 1.68, 95% CI: 1.44–1.97). Triple therapy of warfarin-aspirin-clopidogrel was associated with the highest increased risk (RR: 3.75, 95% CI: 2.71–5.19). This large population-based study suggests that while all antithrombotic therapies are associated with an elevated risk of bleeding, the risks increase in an additive fashion with dual and triple therapy, particularly in combinations containing warfarin.

Keywords

Atrial fibrillation - antithrombotic therapies - bleeding - populationbased

Full Text

References

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