Dabigatran Etexilate: An Oral Direct Thrombin Inhibitor for the Management of Thromboembolic Disorders

• Published in: Clinical therapeutics 2012-04, Vol.34 (4), p.766-787
• Main Authors: Cheng, Judy W.M., BS, PharmD, MPH, FCCP, BCPS, Vu, Huyen
• Format: Article
• Language: English
• Subjects: Adult; Aged; Anticoagulants; Area Under Curve; atrial fibrillation; Benzimidazoles - pharmacokinetics; Benzimidazoles - therapeutic use; Biological and medical sciences; Biological Availability; Blood and lymphatic vessels; Cardiac arrhythmia; Cardiac dysrhythmias; Cardiology. Vascular system; Dabigatran; dabigatran etexilate; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Drug therapy; Female; Heart; Humans; Internal Medicine; Male; Medical Education; Medical sciences; Mortality; Pharmacology. Drug treatments; Prodrugs - pharmacokinetics; Prodrugs - therapeutic use; Pyridines - pharmacokinetics; Pyridines - therapeutic use; Randomized Controlled Trials as Topic; Stroke; Thromboembolism - drug therapy; Thromboembolism - prevention & control; venous thromboembolism
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2012.02.022

Abstract Background Until recently, warfarin was the only oral anticoagulant available in the United States. Its narrow therapeutic index, interpatient variability in dose response, and drug and food interactions make it difficult to use. Dabigatran etexilate (DE) is a new oral direct thrombin inhibitor that was approved in the US and in Canada for the prevention of thromboembolic events in patients with atrial fibrillation (AF), as well as in Europe and Canada for the prevention of venous thromboembolism (VTE). Objective To discuss the role of DE for the prevention and treatment of VTE, as well as for the prevention of stroke in patients with AF. Methods Peer-reviewed clinical trials, review articles, and treatment guidelines were identified from MEDLINE and the Current Contents database (both 1966–February 15, 2012) using the search terms dabigatran, VTE, Afib, pharmacokinetics, pharmacodynamics, pharmacoeconomics, and cost-effectiveness . Citations from available articles were also reviewed for additional references. Results For VTE prophylaxis, DE 150 or 220 mg orally daily has demonstrated either superiority or noninferiority to subcutaneous enoxaparin once daily in most studies. However, one study failed to demonstrate noninferiority to subcutaneous enoxaparin dosed BID in the composite end point of VTE, and all-cause mortality. For VTE treatment, DE 150 mg BID orally was shown to be noninferior to warfarin in preventing recurrent events. For AF, DE 150 mg BID orally is superior to warfarin in the prevention of thromboembolism, whereas 110 mg BID is noninferior to warfarin. Pharmacoeconomic analyses performed in the United Kingdom and Ireland found that DE can be cost-saving compared with enoxaparin in the prevention of VTE. Adverse effects of DE reported in clinical studies include dyspepsia (12%–13%) and bleeding (minor bleeding: 6%–22%). Conclusions DE exhibited a safety profile and efficacy comparable to enoxaparin for VTE prophylaxis; comparable safety profile and efficacy to warfarin for VTE treatment; and superiority (150 mg BID orally) in the prevention of stroke and systemic embolism compared with warfarin in patients with AF. The relative ease of oral administration, no need for routine monitoring, and lack of significant drug interactions, may favor use of DE over other anticoagulants. However, there is no antidote for DE currently available.