The direct thrombin inhibitor ximelagatran/melagatran: a systematic review on clinical applications and an evidence based assessment of risk benefit profile.
The direct thrombin inhibitor, ximelagatran, and its active form, melagatran (X/M), have been compared against conventional anticoagulant therapy (CAT) in many clinical settings. Their risk-benefit profile drove large debate until withdrawal by the manufacturer. A systematic review of all published randomized trials has been performed and a meta-analysis of randomised controlled trial (RCT) of X/M versus CAT. Major medical databases were searched for RCTs. Major adverse events (MAE: all cause death, nonfatal myocardial infarction, nonfatal thromboembolic stroke, pulmonary embolism), major bleeds (MB), minor bleeds and the rate of hepatotoxicity (HT) were compared. In terms of efficacy, X/M was at least as effective as, or even superior to, CAT. In terms of safety, the overall risk of MAE, MB, minor bleeds and HT was not significantly different for X/M compared with CAT. According to individual clinical settings, X/M was associated with a lower risk of MB but a prohibitive higher risk of HT in those clinical settings requiring prolonged treatment.
Testa
Luca
L
Institute of Cardiology, John Radcliffe Hospital, Oxford, UK. luctes@gmail.com
Bhindi
Ravinai
R
Agostoni
Pierfrancesco
P
Abbate
Antonio
A
Zoccai
Guiseppe Gl Biondi
GG
van Gaal
William J
WJ
D000818:Animals; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D000991:Antithrombins / Q000009:adverse effects* / Q000627:therapeutic use; D001384:Azetidines / Q000009:adverse effects* / Q000627:therapeutic use*; D001596:Benzylamines / Q000009:adverse effects* / Q000627:therapeutic use*; D019317:Evidence-Based Medicine / Q000379:methods*; D006801:Humans; D018570:Risk Assessment; D013917:Thrombin / Q000037:antagonists & inhibitors*
D000925:Anticoagulants; D000991:Antithrombins; D001384:Azetidines; D001596:Benzylamines; C109573:melagatran; C426686:ximelagatran; D013917:Thrombin