A comparison of dabigatran etexilate with warfarin in patients with mechanical heart valves: THE Randomized, phase II study to evaluate the safety and pharmacokinetics of oral dabigatran etexilate in patients after heart valve replacement (RE-ALIGN).

BACKGROUND: Vitamin K antagonists are the only oral anticoagulants approved for long-term treatment of patients with a cardiac valve replacement. OBJECTIVE: This study aims to test a new dosing regimen for dabigatran etexilate in patients with a mechanical bileaflet valve. METHODS: Patients aged ≥ 18 years and ≤ 75 years, either undergoing implantation of a mechanical bileaflet valve (aortic or mitral or both) during the current hospital stay or having undergone implantation a mitral bileaflet valve >3 months before randomization, will be randomized between dabigatran etexilate or warfarin (in a ratio of 2:1) in an open-label design. Initial doses of dabigatran will be based on the estimated creatinine clearance, and the doses will be adjusted based on measuring trough dabigatran plasma levels to achieve levels ≥ 50 ng/mL at steady state. Doses will range between 150 mg twice a day and 300 mg twice a day. Warfarin management and target international normalized ratio will be according to current practice guidelines at the discretion of the treating physicians. The plan is to treat 270 patients with dabigatran etexilate for a total study population of approximately 405 patients. Clinical efficacy and safety outcomes will be analyzed in an exploratory manner. CONCLUSIONS: RE-ALIGN is the first study to test an alternative to warfarin in patients with mechanical heart valves. A definitive phase III study will be planned based on the results of this study.

Antithrombin-α for the prophylaxis of venous thrombosis in congenital antithrombin deficiency.

ATryn(®) is a transgenically produced recombinant antithrombin (AT) concentrate licensed in Europe and the USA for the thromboprophylaxis of hereditary AT-deficient patients undergoing surgical procedures who are at a high risk of venous thromboembolism. It is also licensed, in the USA only, for prevention the of venous thromboembolism in association with delivery and the immediate post-partum period. ATryn is administered as a continuous intravenous infusion, with weight-adjusted loading and maintenance dosing regimens. Recombinant AT has an identical amino acid structure with minor glycosylation differences to endogenous AT. ATryn has a shorter half-life but an equivalent efficacy to that of plasma-derived AT concentrates in the prevention of venous thromboembolism in this rare distinct group with a high thrombotic risk. In addition, this recombinant product should be free from the risk of human viral or prion transmission.