NEW YORK (Reuters Health) – In patients with atrial fibrillation (AF), combination antithrombotic therapy with an anticoagulant and an antiplatelet increases the risk for clinically relevant bleeding with no significant reduction in stroke risk, a post hoc analysis of the AMADEUS trial confirms.

AF often coexists with atherosclerotic vascular disease and therefore many patients with AF on anticoagulation therapy are also on concomitant antiplatelet therapy, Deirdre Lane of the University of Birmingham Centre for Cardiovascular Sciences in Birmingham, England and colleagues note in the July issue of Chest.

They assessed the impact of combination antithrombotic therapy on stroke and bleeding risk in 4,576 patients with AF who participated in the AMADEUS trial; 2,283 received subcutaneous idraparinux and 2,293 received adjusted-dose vitamin K antagonists (warfarin or acenocoumarol). In addition to anticoagulation therapy, 848 of these patients also received antiplatelet therapy (aspirin, clopidogrel, ticlopidine, etc).

The trial was stopped prematurely after a mean follow-up of 10.7 months due to an excess of major bleeding and clinically relevant bleeding with idraparinux compared with vitamin K antagonists (346 cases, 19.7/100 patient years versus 226 cases, 11.3/100 patient-years; P < 0.001).

In the post hoc analysis, the researchers say they detected 572 clinically relevant bleeding episodes (15.3% per year) and 103 major bleeding episodes (2.6% per year).

Patients receiving combination antithrombotic therapy had a 2.3-fold increased risk for clinically relevant bleeding events and a 2.5-fold increased risk for major bleeding events, compared with those receiving anticoagulation therapy only.

Multivariate analysis revealed that the risk of clinically relevant bleeding was significantly increased in patients aged 65 to 74 years (hazard ratio, 1.44) and those aged 75 and older (hazard ratio 1.59) and by combination antithrombotic therapy (hazard ratio 2.47).

The same held true for major bleeding events; patients aged 65 to 74 years, aged 75 and older, and those receiving combination antithrombotic therapy had hazard ratios of 2.26, 4.19 and 2.23, respectively.

Importantly, note the researchers, combination therapy did not reduce the risk for ischemic stroke compared with anticoagulation therapy only. In fact, there was a trend toward more ischemic strokes occurring with combination antithrombotic therapy compared with anticoagulation therapy alone.

Based on these findings, the researchers say “combination antithrombotic therapy is justified only in patients with a clear indication that the benefit of adding antiplatelet therapy to anticoagulant treatment outweighs the increased risk of bleeding.”

Chest 2011;140:146-155.