FDA Approves Dabigatran for Stroke Prevention

Praise the Lord and pass the loot

, an alternative to warfarin is now available. Yesterday the FDA approved dabigatran (Pradaxa; Boehringer Ingelheim), a direct thrombin inhibitor, for the prevention of stroke and other systemic embolic events in patients with a-fib. The pill's approval comes exactly 1 month after an FDA advisory panel unanimously (9-0) endorsed the drug. The pill's main advantage is that its use does not necessitate the neverending chore of anticoagulation monitoring (eg, repeated protime assessments)—unlike treatment with the old-as-dirt warfarin.

Dabigatran's approval for the a-fib indication is based on the mammoth (N = 18,113) unblinded RE-LY trial,* in which the drug, at 2 dosages (110 and 150 mg BID), was either comparable or superior** to warfarin. What's confusing about yesterday's approval, however, is that a 75-mg dosage, not a 110-mg pill, got an FDA nod, in addition to the 150-mg BID regimen. Why the 110-mg pill is not available in the United States (but is available in Europe) is a bit of a mystery. According to heartwire, the 75-mg pill, BID, is available for "a small subset with severe renal impairment." One forum post at heartwire indicates that the 75-mg dosage was studied in early pharmacokinetics trials. Cardiologist Sanjay Kaul told heartwire, "The 110-mg dose, while associated with reduced bleeding, had a 12% higher incidence of ischemic stroke. In my opinion, it would not offer much of an advantage over warfarin and would likely be an ineffective alternative."

Data on US-based costs for Pradaxa are currently elusive. According to PharmacyChecker.com, a 1-month supply of 110-mg capsules ranges from $258 to $394 and some change. While warfarin, including brand-name Coumadin, is much, much cheaper, BI will no doubt consider the avoided direct and indirect costs of anticoagulation monitoring with warfarin and the reduced burden of prevented strokes when justifying its US price for Pradaxa.

N.B. Boehringer Ingelheim is a privately held German company.

RE-LY = Randomized Evaluation of Long-term Anticoagulant Therapy.

* RE-LY used the increasingly popular PROBE protocol, a prospective, randomized, open-label, blinded endpoint evaluation.

** 35% stroke risk reduction with 150 mg BID. The absolute stroke risk reduction was 1.69% - 1.11% = 0.58%. Rates of major bleeding and mortality were similar with the 2 treatments. The annual rate of hemorrhagic stroke was lower with dabigatran 150 mg BID (0.10% vs 0.38% with warfarin; P < .001).