Incidence and Management of Ischemic Stroke and Intracerebral Hemorrhage in Patients on Dabigatran Etexilate Treatment
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REVIEW
Incidence and Management of Ischemic Stroke and Intracerebral Hemorrhage in Patients on Dabigatran Etexilate Treatment Masaki Watanabe • Fazeel M. Siddiqui Adnan I. Qureshi
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Published online: 12 July 2011 Ó Springer Science+Business Media, LLC 2011
Abstract Dabigatran etexilate is an oral, reversible direct thrombin inhibitor and has been recently approved for the prevention of stroke in patients with non-valvular atrial fibrillation. This review describes the incidence and management of stroke and related complications in patients on dabigatran etexilate. Dabigatran is a rapidly acting, and highly selective and reversible inhibitor of thrombin. It also has a potent inhibitory effect on thrombin-induced platelet aggregation, making it effective in preventing both venous and arterial thrombosis. The activated partial thromboplastin time, ecarin clotting time and thrombin time are sensitive tests to evaluate the anticoagulant effects of dabigatran. The rate of ischemic stroke is significantly lower in patients on 150 mg of dabigatran etexilate as compared to 110-mg dose or warfarin (9.2, 13.4, 12 per 1,000 patients, respectively). As there is no standard coagulation test for dabigatran; treatment of acute stroke in such patients is debatable. Careful clinical consideration is required before administering thrombolytic therapy in this patient population. The rate of hemorrhagic stroke was 1.2 and 1.0 per 1,000 patients treated on 110 and 150 mg of dabigatran, respectively. As there is no specific antidote, the only treatment option is discontinuation of the drug and supportive management. Other treatment options, though not clinically proven, include specific reversal agents, which can be individualized according to the severity of the hemorrhage. Dabigatran should be discontinued before M. Watanabe A. I. Qureshi (&) Zeenat Qureshi Stroke Research Center, University of Minnesota, Minneapolis, MN 55455, USA e-mail: [email protected] F. M. Siddiqui Department of Neurology, Southern Illinois University Health Care, Springfield, IL, USA
invasive procedures depending on the degree of renal impairment and risk of bleeding. Keywords Dabigatran Dabigatran etexilate Direct thrombin inhibitor Stroke Ischemic stroke Intracranial hemorrhage Atrial fibrillation
Background and Introduction Atrial fibrillation affects approximately 2.3 million Americans [1] and remains a major cause of severe disabling stroke [2]. For decades, warfarin, a vitamin K antagonist, was the only effective oral anticoagulant treatment for preventing embolic events in patients with atrial fibrillation [3]. Six randomized controlled trials and two meta-analyses have demonstrated the benefit of warfarin in reducing the risk of ischemic stroke in patients with atrial fibrillation [4– 11]. However, warfarin use requires frequent drug level monitoring because of variable drug activity, narrow therapeutic index, and interactions with food and other commonly used medications (especially those that are metabolized through P450-cytochro
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