Abstract 5619: Bleeding With Clopidogrel Plus Aspirin in Stroke Prevention in Atrial Fibrillation Compared to Bleeding With Warfarin: Lessons From ACTIVE-W and ACTIVE-A

Rationale : Many patients with atrial fibrillation (AF) are felt ineligible for warfarin often due to a perceived unacceptable bleeding risk. Aspirin was shown to be an inferior alternative. In warfarin eligible patients in the large ACTIVE-W study stroke prevention with aspirin plus clopidogrel (A+C) was inferior to warfarin, whereas bleeding with A+C was unexpectedly quite similar to that of warfarin. Recently, in patients ineligible for warfarin in the large ACTIVE-A trial A+C was found to be superior to aspirin alone against stroke, but at the cost of a significantly increased risk of bleeding including hemorrhagic stroke. Here we put both trials into perspective with regard to safety, efficacy and trade-off. Methods : In ACTIVE-W patients eligible for warfarin (n=6,706) were randomized to warfarin or A+C and followed for 1.8 year (y) when the trial was stopped prematurely. Patients ineligible for warfarin (n=7,554) were randomized in ACTIVE-A to A+C or aspirin alone and followed for 3.6 y. Clopidogrel dose was 75 mg and aspirin dose 75–100 mg daily in both trials. Results: Baseline risk was highly comparable in both ACTIVE-trials (table ). Conclusions : The lowest stroke rate is seen with warfarin. Major bleeding with A+C is rather similar in both trials and comparable with warfarin. Given the bleeding with A+C in both warfarin eligible and ineligible patients, warfarin has the most favorable trade-off. These results suggest that perceived bleeding risk per se does not make AF patients ineligible for warfarin. Thus, warfarin should remain the cornerstone for stroke prevention in AF.