Tuesday, January 18, 2011

Dabigatran for stroke prevention in atrial fibrillation: is it worth it?

For most patients with paroxysmal or persistent atrial fibrillation, anticoagulation with warfarin is recommended to reduce the risk of thromboembolic stroke. This recommendation generally requires that a patient come in for frequent International Normalized Ratio (INR) measurements, adjusting the dose of warfarin as needed to keep him or her in a narrow therapeutic range, and avoiding a long list of medications that alter warfarin metabolism. However, a review of diagnosis and treatment of atrial fibrillation in the January 1st issue of AFP describes an alternative:

The anticoagulation agent dabigatran, a direct thrombin inhibitor, was recently approved by the U.S. Food and Drug Administration for the prevention of stroke and systemic embolism with atrial fibrillation. In a randomized trial, 150 mg of dabigatran twice per day was shown to be superior to warfarin in decreasing the incidence of ischemic and hemorrhagic strokes. Patients assigned to dabigatran had a higher incidence of myocardial infarction than those assigned to warfarin, but the difference was not statistically significant.

As we will describe in a future STEPS article, clinical trials have shown dabigatran to be at least as effective at preventing strokes in patients with atrial fibrillation compared to warfarin, with a similar side effect profile. Its advantages over warfarin are that laboratory monitoring and dose adjustment are not required, and that dabigatran appears to have far fewer drug-drug interactions. That being said, a month's supply of dabigatran costs about $200, compared to $10 for warfarin. So is the increased cost worth it?

There are at least three approaches to answering this question:

1) Can the patient afford the drug? Does his or her health insurance cover it? If so, prescribe. If not, don't.

2) A cost-effectiveness analysis recently published in the Annals of Internal Medicine suggested that "dabigatran may be a cost-effective alternative to warfarin depending on pricing," although this analysis was based on a number of assumptions and data from a single industry-sponsored randomized trial with only two years of follow-up.

3) As is the case for many evidence-based interventions, many patients with atrial fibrillation who should be taking warfarin are not. In a study that AFP previously summarized in Tips From Other Journals, researchers described a "break-even point" at which "as many lives are saved by creating a new drug as by maximizing the delivery of established drugs." Would increasing the proportion of eligible patients taking any anticoagulant drug lead to a greater population-level benefit than switching every patient who is already using warfarin to dabigatran?

Primary care physicians may not be used to examining individual medical problems from a population health perspective, and in deciding whether to prescribe dabigatran or warfarin in day-to-day practice, option #1 is likely to be the most practical and widely used. But in an era in which the annual rise in U.S. prescription drug costs consistently outpaces inflation, ignoring the broader view is no longer an option.