Elsevier

American Heart Journal

Volume 152, Issue 5, November 2006, Pages 967-973
American Heart Journal

Clinical Investigation
Electrophysiology
Risks and benefits of combining aspirin with anticoagulant therapy in patients with atrial fibrillation: An exploratory analysis of stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) trials

https://doi.org/10.1016/j.ahj.2006.06.024Get rights and content

Background

Aspirin is used in combination with anticoagulant therapy in patients with atrial fibrillation (AF), but evidence of additional efficacy is not available.

Methods

We compared ischemic events and bleeding in the SPORTIF III and IV randomized trials of anticoagulation with warfarin (international normalized ratio 2-3) or fixed-dose ximelagatran. Low-dose aspirin (<100 mg/d) was allowed based on prevailing guidelines.

Results

The 14% of patients receiving aspirin more often had diabetes (27.5% vs 23%, P < .01), coronary artery disease (69% vs 41%, P < .01), previous stroke or transient ischemic attack (26% vs 20%, P < .01), and left ventricular dysfunction (41% vs 36%, P < .01). Addition of aspirin to either warfarin or ximelagatran was associated with no reduction in stroke or systemic embolism. Major bleeding occurred significantly more often with aspirin plus warfarin (3.9% per year) than with warfarin alone (2.3% per year, P < .01), aspirin plus ximelagatran (2.0% per year), or ximelagatran alone (1.9% per year). The rate of myocardial infarction with aspirin and warfarin (0.6% per year) was not significantly different from that with ximelagatran alone (1.0% per year), warfarin alone (1.0% per year), or aspirin and ximelagatran (1.4% per year).

Conclusions

Aspirin combined with anticoagulant therapy was associated with no reduction in stroke, systemic embolism, or myocardial infarction in patients with AF. Aspirin combined with warfarin was associated with an incremental rate of major bleeding of 1.6% per year. No increased major bleeding occurred with aspirin and ximelagatran. These results suggest that the risks associated with addition of aspirin to anticoagulation in patients with AF outweigh the benefit.

Section snippets

Methods

The rationale, design, and main results of the SPORTIF III and V studies have been published elsewhere.9, 10, 11 In brief, these randomized multicenter trials were designed to demonstrate the noninferiority of the oral direct thrombin inhibitor ximelagatran (36 mg twice daily), compared with vitamin K antagonist therapy with adjusted-dose warfarin (international normalized ratio [INR] 2-3) for prevention of all stroke and systemic embolism in high-risk patients with nonvalvular AF enrolled in

Results

Of the 7329 enrolled patients (3407 patients in SPORTIF III and 3922 patients in SPORTIF V), concurrent medication logs were unavailable for 25 patients, leaving data from 7304 patients available for secondary analysis. Of these, aspirin was prescribed to 531 patients in the ximelagatran group and 481 patients in the warfarin group. Thus, the current study compared the following groups at baseline: ximelagatran (n = 3120), ximelagatran plus aspirin (n = 531), warfarin (n = 3172), and warfarin

Discussion

This post hoc analysis involves patients given aspirin in addition to randomized anticoagulant therapy (either warfarin or ximelagatran) under a protocol that prohibited aspirin, except in limited dosage for patients considered at high risk, usually because of a clinical history of CAD. Patients taking aspirin on the advice of their physicians were therefore generally at higher risk for developing the cardiovascular events that served as end points in these studies. The combination of aspirin

References (18)

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i

Drs Flaker, Connolly, Goldman, and Halinen have received research grants from AstraZeneca.

j

Drs Flaker, Connolly, and Halinen are on the AstraZeneca speaker's bureau.

k

Dr Vahanian and Dr Halperin are consultants to AstraZeneca.

l

Dr Horrow is an employee of AstraZeneca.

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