Should you add aspirin to your heart patient's warfarin regimen?

Journal of Family Practice, June, 2007

Dentali F, Douketis JD, Lira W, Crowther M. Combined aspirinoral anticoagulant therapy compared with oral anticoagulant therapy alone among patients at risk for cardiovascular disease. A meta-analysis of randomized trials. Arch Intern Med 2007; 167:117-124.

Clinical question

Does the practice of adding low-dose aspirin to oral anticoagulant (warfarin) regimens actually benefit cardiac patients?

Bottom line

No, it does not reduce the risk of death or thromboembolism in patients with atrial fibrillation or coronary artery disease. It does, however, benefit patients with mechanical heart valves.

Level of evidence

1a: systematic review (with homogeneity) of randomized controlled trials

Study design

Meta-analysis (randomized controlled trials)

Funding

Foundation

Setting

Various (meta-analysis)

Synopsis

The researchers assembled and combined randomized studies of at least 3 months' duration that compared warfarin plus aspirin with warfarin alone, in trials where warfarin was administered to achieve the same target international normalized ratio (INR) or was given at the same fixed dose in both treatment arms. The authors searched 3 databases, reviewed reference lists, and contacted experts to find 10 studies (including more than 4000 patients) that met their criteria. Two authors independently evaluated the research using a modified version of the Jadad criteria and extracted the data.

Five studies evaluated the use of the combination in patients with mechanical heart valves, and the other 5 included patients with atrial fibrillation, with coronary artery disease, or at high risk for cardiovascular disease. Doses of aspirin ranged from <100 mg/day to 1000 mg/ day; warfarin was dosed to obtain a target INR of at least 1.8 in 8 of the studies and 2.0 or higher in 2 studies.

Overall, major bleeding was more likely to occur when the combination was used (number needed to harm=100). Mortality due to any cause was not reduced by the addition of aspirin.

There was no evidence of publication bias, and the result showed homogeneity among the studies.

Subgroup analysis showed a benefit for some

However, a subgroup analysis showed that for patients with mechanical heart valves, the addition of aspirin decreased the risk of thromboembolism (odds ratio=0.27; 95% confidence interval, 0.15-0.49) but also increased the risk of bleeding. For those patients with heart disease or atrial fibrillation, the addition of aspirin did not decrease the risk for thromboembolism.

FAST TRACK Adding aspirin to warfarin did not reduce the risk of thromboembolism in patients with atrial fibrillation or CAD