As the population ages, the burden of thromboembolic disease increases. The development of new
anticoagulants that overcome the shortcomings of the
vitamin K antagonists represents an important advance.Clinical evaluation of new
anticoagulants typically begins in short-term indications, such as prophylaxis against
venous thromboembolism in patients undergoing orthopaedic surgery, followed by investigation in
chronic conditions, such as
stroke prevention in patients with
atrial fibrillation. Factors for consideration in clinical trials include methodological issues (blinded versus open-label; active-control statistical designs; patient selection, etc.). Despite its subsequent withdrawal, clinical trials of
ximelagatran demonstrated the efficacy of fixed doses of an oral,
direct thrombin inhibitor for prevention of
thromboembolism. Direct and indirect inhibition of
activated Factor X is another target for new
anticoagulants. Evidence-based data from trials such as these will pave the way for new
anticoagulants, with the goal of bringing optimum prophylactic
therapy to those requiring anticoagulation.