Dabigatran (Pradaxa)for Prevention of Stroke in Atrial Fibrillation

Dabigatran (Pradaxa)is an orally administered direct thrombin inhibitor labeledfor the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Unlikewarfarin (Coumadin), it does not induce anticoagulation through depletion of clotting factors, but through an immediate effect on thrombin, the last step in the coagulation cascade that causes clotformation.

Drug	Dosage	Doseform	Cost of full course [*]
Dabigatran (Pradaxa)	150 mg twice daily; 75 mg twice daily in patients with impaired renal function	75- and 150-mg capsules	$246for 60 150-mg capsules

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*	—Estimated retail price of one month's treatment based on information obtained at http://www.blogger.com/website/view?area=be&URL=http://www.drugstore.com (accessed October 25, 2010).

Safety Tolerability Effectiveness Price Simplicity

Dabigatran increases the risk of minor and major bleeding. In a randomized controlled trial ofdabigatran compared with dose-adjustedwarfarin (International Normalized Ratio of 2.0 to 3.0) in more than 18,000 patients with atrial fibrillation, life-threatening bleeding and intracranial hemorrhage occurred less often withdabigatran, with one fewer patient experiencing an intracranial hemorrhagefor every 117 patients treated withdabigatran instead ofwarfarin (number needed to treat [NNT] = 117; 95% confidence interval [CI], 82 to 201).^[1]Although gastrointestinal bleeding occurs more often withdabigatran, the incidence of minor bleedingis lower (NNT = 37; 95% CI, 23 to 99).^[1]Unlikewarfarin,dabigatran lacks significant drug interactions. However, the concurrent use of antiplatelet agents, heparin, or long-term nonsteroidal anti-inflammatory drugs may increase the risk of bleeding. Thereis no reversal agentfordabigatran. Itis renally eliminated, and the dosage must be reduced in patients with a creatinine clearance of less than 30 mL per minute per 1.73 m² (0.50 mL per second per m²).^[2]Dabigatran has not been studied in children or in pregnant or breastfeeding women. Itis a U.S Food and Drug Administration pregnancy category C drug.

In clinical trials, more patients receivingdabigatran withdrew because of adverse effects compared with those receivingwarfarin.Dabigatran causes dyspepsia and gastritis symptoms in about one-third of patients.

Dabigatran has been compared with enoxaparin (Lovenox) andwarfarin in randomized controlled trials. In a study of 18,000 patients with atrial fibrillation, those who receiveddabigatran had significantly fewerischemic strokes than those who receivedwarfarin for a median of two years (NNT = 91; 95% CI, 59 to 194).^[1]Dabigatran has been studiedfor surgery prophylaxis (versus enoxaparin) andfor the treatment of deep venous thrombosis and pulmonary embolism (versuswarfarin), but itis not labeledfor these uses

A one-month supply of 150-mgdabigatran capsules costs approximately $246; a one-month supply of genericwarfarin costs approximately $15.^[6]The lack of laboratory monitoring or office visitsfor dose titration may partially offset this difference.

Dabigatran produces an effect on coagulation in 30 to 90 minutes, has a predictable response, does not require routine laboratory monitoring, and does not have the drug and food interactions that can be problematic withwarfarin therapy. Patient compliance with twice-daily dosing must be stressed. The dose ofdabigatran is fixed and does not require titration when therapyis initiated or discontinued.

Bottom Line

Dabigatran is superior towarfarin for stroke prevention in patients with atrial fibrillation, with similar rates of major bleeding. Because it does not require laboratory monitoring,dabigatran therapyis less complicated thanwarfarin therapy, but it costs significantly more