HAMILTON, ONTARIO, CANADA. Although there is no evidence that otherwise healthy lone afibbers have an increased risk of ischemic stroke, it is clear that atrial fibrillation (AF) patients with heart failure, diabetes or hypertension have a significantly increased risk and this risk is further magnified if the patient has already suffered a heart attack or stroke. To date, oral anticoagulation with vitamin K antagonists such as warfarin (Coumadin) is still considered to be the best preventive therapy for patients at risk for stroke. Unfortunately, warfarin interacts with many foods and drugs and treatment requires constant, costly monitoring. Its use also substantially increases the risk of hemorrhagic stroke and major internal bleeding, particularly in older people, a group that, ironically, is also most at risk for an ischemic stroke. It is therefore not surprising that a vast amount of medical research is being directed at finding a replacement for warfarin.
Warfarin acts by inhibiting the activation of the vitamin K-dependent coagulation factors V, VII, and X in the extrinsic and common pathways of the coagulation cascade. Research aimed at replacing warfarin essentially focuses on developing new pharmaceutical drugs which will inhibit specific coagulation factors. A new direct thrombin inhibitor dabigatran etexilate (Pradax) has successfully undergone 3 large-scale phase III trials for the treatment of deep vein thrombosis (DVT). A recent trial involving 502 AF patients with at least one additional risk factor for stroke found that 150 mg of dabigatran twice a day is as effective and safe as standard warfarin therapy.
Now a very large group of researchers from 41 countries reports on a trial involving over 18,000 atrial fibrillation patients who had one or more risk factors for stroke (average CHADS2 score was 2.1). NOTE: 79% of the participants had hypertension, 32% had heart failure, 20% had experienced a prior heart attack or stroke, and 23% had diabetes. The study participants were randomly allocated to receive 110 or 150 mg of dabigatran twice daily or standard warfarin therapy (INR range aim of 2.0 to 3.0). The patients were re-examined 2 weeks and 1 and 2 months after randomization, every 3 months thereafter in the first year, and then every 4 months until the end of the 2-year follow-up period. The INR of warfarin users was checked monthly, but no monitoring of blood levels of dabigatran was required.
A comparison of the incidence of ischemic stroke and systemic embolism, hemorrhagic stroke, major bleeding, heart attack, and overall mortality is shown below: