Dabigatran versus Warfarin in Patients with Atrial Fibrillation

To the Editor: Although Connolly et al. (Sept. 17 issue)1 have demonstrated a modest advantage for dabigatran over warfarin in atrial fibrillation, we think the benefit could be even greater. Warfarin has many adverse properties. Vitamin K content varies widely in foods. Warfarin inhibits the synthesis of sequential enzymes in the coagulation cascade, which imparts a drastically steep dose\u96response relationship. The binding of warfarin to plasma proteins and its metabolism by cytochrome P-450 enzymes facilitate drug interactions. These properties result in variability in anticoagulant control, which is associated with bleeding, thrombosis, and increased risk of death.2-5 Dabigatran lacks these undesirable properties. But the adoption of \u93one size fits all\u94 dosing has probably undermined the performance of dabigatran in the trial for the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY). Dabigatran appeared to be more efficacious in patients who weighed less and in patients with impaired renal function (in whom the drug accumulates), pointing to significant interpatient variability in response. Individualized dosing, based on weight and estimated creatinine clearance, might improve the drug\u92s risk\u96benefit ratio. Dosing could be further refined with the use of a single measurement of the drug level drawn at steady state, if necessary. Such an approach should be studied. Donald Stuart Houston, M.D., Ph.D. Ryan Zarychanski, M.D