- MY ACCOUNT
Hamilton, Canada: A new study (1) comparing dabigatran with warfarin in patients with mechanical heart valves showed that anticoagulation with dabigatran for patients with mechanical heart valves resulted in higher incidence of complications( thromboembolic and bleeding events). Therefore dabigatran should not used in patients with mechanical heart valves.
The efficacy of Dabigatran for prevention of stroke in patients with atrial fibrillation was demonstrated in RE-LY trial. Dabigatran was also effective in decreasing valve thrombosis. Therefore RE-ALIGN (Randomized, Phase II Study to Evaluate the Safety and Pharmacokinetics of Oral Dabigatran Etexilate in Patients after Heart Valve Replacement) trial was undertaken to demonstrate the efficacy of Dabigatran in patients with mechanical heart valves. RE-ALIGN trial was a prospective, randomized, multicenter, international, phase 2 open label trial comparing dabigatran with warfarin in patients with (i)) recent implantation (< 7 days) of mechanical bileaflet aortic or mitral valve(group A) and (ii) remote implantation (>3 months) of mechanical mitral valve (group B).
Patients in both groups were randomized in 2:1 ratio to receive either dabigatran or warfarin. After enrolling 252 patients (168 in dabigatran arm and 84 in warfarin arm, 199 in group A and 53 in group B), the study was prematurely stopped due to increased rates of bleeding and thromboembolic events in dabigatran arm. As per the study protocol, the target plasma trough level was set at 50 mg per milliliter. In 39 patients, increase in dabigatran dose was needed to achieve the target plasma concentration. Dabigatran was discontinued in 13 (8%) patients as target trough concentrations could not be achieved with dose of 300 mg twice daily.
The composite of death (1), stroke (9), transient ischemic attack (3), systemic embolism and myocardial infarction (3) was higher in dabigatran arm (9% vs 5%, hazard ratio 1.94, p = 0.24). Valve thrombosis was noted only in dabigatran group (5 patients). Bleeding events were significantly higher in dabigatran group (27% vs 12% , HR 2.45 , p =0.01). All major bleeding was pericardial in location which occurred only group A( 4% vs 2% , HR 1.76, p =0.48).
This study showed that dabigatran is not a suitable drug for anticoagulation in patients with mechanical valves as there is increased risk of thromboembolic and bleeding events in this patient population. This is probably because of different mechanism of thrombus formation in these patients. Trials studying the use of rivaroxaban for anticoagulation in patient with mechanical heart valves are in preliminary stages. It would be interesting to see whether these novel anticoagulant drugs are effective for prevention of stroke in this patient population.
Reference: 1. Eikelboom JW, Connolly SJ, Brueckmann M, Granger CB, Kappetein AP, Mack MJ, et al. Dabigatran versus Warfarin in Patients with Mechanical Heart Valves. The New England journal of medicine. 2013. Epub 2013/09/03. doi: 10.1056/NEJMoa1300615. PubMed PMID: 23991661
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