Melagatran for thromboprophylaxis after mechanical valve implantation: results in a heterotopic porcine model.
OBJECTIVE
Melagatran, the active form of ximelagatran, is a novel, direct thrombin inhibitor that does not have a narrow therapeutic window regarding hemorrhagic and thromboembolic events. We aimed to determine whether melagatran would be effective in preventing thrombus formation on heterotopically placed mechanical heart valves.


METHODS
A graft containing a bileaflet mechanical heart valve was implanted in the descending thoracic aorta of domestic swine. Two groups of 6 animals received daily subcutaneous injections of either melagatran (2.4 mg/kg, 3 times per day) or dalteparin (175 U/kg, 2 times per day) for 30 days. Four control animals received no anticoagulation therapy. Fecal HemoQuant and serum hemoglobin levels were recorded. Thirty days after the procedure, platelets were labeled with indium 111, the abdominal organs were inspected, and thrombi and platelets deposited on the valve were measured.


RESULTS
Median thrombus burden on the valves was 0.4 mg (interquartile range, 0.15-5.45 mg) with melagatran, 0.5 mg (interquartile range, 0-14.5 mg) with dalteparin, and 168 mg (interquartile range, 32.5-665.75 mg) for controls (melagatran vs dalteparin and control; P = .04). Median platelet deposition on the valves was 0 (interquartile range, 0-8.9 x 10(4)) with melagatran, 49.9 x 10(4) (interquartile range, 27.9 x 104-191.8 x 10(4)) with dalteparin, and 115.2 x 10(4) (interquartile range, 9.6 x 10(4)-243 x 10(4)) for controls (melagatran vs dalteparin and control; P = .02). Melagatran did not increase the risk of thromboembolism or bleeding.


CONCLUSIONS
Thrombus and platelet accumulation on the prosthetic valves was decreased by melagatran and dalteparin. The use of melagatran or other related direct thrombin inhibitors warrants further study in prophylaxis of thromboembolism in patients with mechanical heart valves.
Thompson
Jess L
JL
Division of Cardiovascular Surgery, Mayo Clinic, Rochester, Minn 55905, USA.
Hamner
Chad E
CE
Potter
D Dean
DD
Lewin
Matthew
M
Sundt
Thoralf M
TM
Schaff
Hartzell V
HV
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001384:Azetidines / Q000494:pharmacology*; D001596:Benzylamines / Q000494:pharmacology*; D017985:Dalteparin / Q000494:pharmacology; D019918:Heart Valve Prosthesis Implantation / Q000009:adverse effects*; D011897:Random Allocation; D018709:Statistics, Nonparametric; D013552:Swine; D013923:Thromboembolism / Q000209:etiology / Q000517:prevention & control*
D000925:Anticoagulants; D001384:Azetidines; D001596:Benzylamines; C109573:melagatran; D017985:Dalteparin