Oral anticoagulation: preparing for change.

摘要

Thromboembolic disorders-stroke and venous thromboembolism (VTE)-pose a substantial risk for mortality and morbidity. Primarily affecting individuals with atrial fibrillation (AF) in their 7(th) and 8(th) decades of life, these disorders will represent a growing burden as aging baby boomers expand the pool of at-risk patients in coming decades, underscoring the need for effective, well tolerated long-term prophylactic therapy. Oral warfarin, the current cornerstone of preventative therapy for these conditions, is associated with a host of barriers-the need for careful dose titration and monitoring, side effects, and drug interactions, among other-that, despite compelling evidence of efficacy, makes it difficult to implement of this agent in at-risk patients. Effective, well-tolerated, and convenient alternatives are needed to maximize oral anticoagulant use and optimize therapy. Several new oral anticoagulants in development offer increased pharmacologic specificity, but only one ximelagatran, has reached late Phase III development. An oral direct thrombin inhibitor, ximelagatran offers a pharmacologic profile that supports twice daily oral administration with minimal drug interactions and a wide therapeutic window that may obviate routine drug-level monitoring, although liver enzyme elevations detected in clinical trials remain an unresolved concern. Further, the results of clinical trials suggest that ximelagatran may be as effective as warfarin in preventing stroke and VTE.