Prosthetic heart valve replacement is performed in several hundred thousand patients per year worldwide and is recommended for many patients with severe valvular heart disease. Bioprosthetic heart valves and mechanical heart valves are the two major valve types. Mechanical valves are more durable than bioprosthetic valves but require lifelong anticoagulant therapy with vitamin K antagonists (warfarin) due to persistent risk of thrombosis and stroke. Warfarin has a narrow therapeutic window and requires frequent monitoring such as international normalized ratio (INR) and restrictions on food, drugs and alcohol. Due to limitations of warfarin many patients prefer bioprosthetic valve replacement rather than a mechanical valve, despite the risk of premature valve failure and repeated valve replacement surgery with bioprosthesis.1 Warfarin works by inhibiting coagulation factors II, VII, IX and X, as well as proteins C and S and hence reduces synthesis of active clotting factors.4
Dabigatran is a direct reversible thrombin inhibitor that has been approved for treatment of nonvalvular atrial fibrillation (AF) based on results of the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) study, but its use for other indications remains untested. It works by inhibiting both free and clot-bound thrombin, which enables the conversion of fibrinogen into fibrin. Dabigatran is eliminated primarily by the kidneys and it’s dosed orally.5
A literature search was conducted using EMBASE database (1980 to 2014 Week 06) and MEDLINE database (1946 to February Week 2 2014) accessed through Ovid. The databases were accessed on February 8, 2014. Keywords included dabigatran etexilate, warfarin, thrombosis, and mechanical heart valves. The terms were combined using the operator “AND”. The search was limited to humans, English Language and adults <18 to 64years >. The search resulted in 3 articles of which one was chosen for thorough evaluation for this consult.
Eikelboom et al performed a phase II dose-validation study on the RE-ALIGN study, which was a prospective, randomized, multi-centered, open label trial that evaluated a new dosing regimen for dabigatran in patients with a mechanical heart valve. The objective of the validation study was to evaluate the use of a new regimen for the administration of dabigatran in patients with mechanical heart valves. The study duration was set for 12 weeks and after which participants could opt to discontinue or continue for up to 84 months. They enrolled 252 patients (67% male), and allotted 168 to dabigatran and the other 84 to warfarin. Only patients between the ages of 18 and 75 years were included for the study and were placed under two groups. The first group (population A) included patients who were undergoing implantation of a mechanical bileaflet valve in the aortic or mitral position or both within the past 7 days whiles patients who had undergone implantation of a...