The Problem

A 67-year-old male with a history of hypertension, hyperlipidemia, atrial fibrillation, and knee degenerative joint disease presents to you for increasing left knee pain. He is currently on atenolol, pravastatin, and warfarin. His CHADS2 score is 1. Prior knee x-rays have shown bilateral tricompartmental narrowing with subchondral sclerosis, in the left knee, more so than in the right. You diagnose him with degenerative joint disease and recommend conservative therapy with another steroid injection. He informs you that the last time you set him up for a joint injection he was turned down because his international normalized ratio (INR) was supertherapeutic. He is also annoyed by having to come in to have his fingerstick INRs. He is an avid investor and read about a Food and Drug Administration approval of a new blood thinner that does not require monitoring. He asks you if this medication would be right for him. You talk to him briefly about dabigatran and report that patients in the higher-dose group (150 mg, b.i.d.) had lower rates of stroke, blood clots, and intracranial hemorrhage (ICH), compared with those who took warfarin but had similar rates of major hemorrhage. You wonder about the costs to the patient and the overall cost-effectiveness of the medication, compared with warfarin.

The Question

Is dabigatran more cost-effective than warfarin for preventing TIA-related stroke?

The Search

You log on to PubMed, enter "dabigatran" and "cost-effectiveness."

Dr. Ebbert and Dr. Tangalos are with the Mayo Clinic in Rochester, Minn. They reported having no conflicts of interest. To respond to this column or suggest topics for consideration, write to Dr. Ebbert and Dr. Tangalos at imnews@elsevier.com.

The Evidence

"Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in atrial fibrillation, (Ann. Intern. Med. 2011;154:1-11).

• Study Design and Data Sources: A decision model analysis of data from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial and other published anticoagulation studies.

• Base Case: Cohort of patients at least age 65 years with a CHADS2 score of at least 1 and no contraindication to anticoagulation.

• Intervention: Anticoagulation with warfarin to an INR 2-3, low-dose dabigatran (110 mg, twice daily), and high dose (150 mg twice daily). We are currently interested in the high dose (150 mg, twice daily) presently because the low dose is not approved in the U.S. presently.

• Outcomes and Assumptions: Event rates were based primarily on the RE-LY study. Quality-adjusted life-years (QALYs), costs (in 2008 U.S. dollars), and incremental cost-effectiveness ratios over a lifetime time horizon were calculated. Costs reflected an ideal insurer covering inpatient and outpatient medical care and prescription costs. For warfarin, the annual medication expenses with the cost for 14 INR tests, the Center for Medicare and Medicaid Services reimbursement for 90-day anticoagulation management CPT code 99363 was used. In the sensitivity analysis, patients initiating warfarin anticoagulation were allowed to have up to 8 additional INR tests and CMS reimbursement at the higher rate allowed for anticoagulation initiation for 90 days (CPT code 99364).

• Results: Total costs were $143,193 for warfarin and $168,398 for high-dose dabigatran. Dabigatran’s cost-effectiveness was heavily influenced by drug cost. High-dose dabigatran was the most cost-effective and most effective therapy, providing an additional 0.56 QALY over warfarin. The incremental cost-effectiveness ratios for high-dose dabigatran was $45,372 per QALY, compared with warfarin. A higher patient baseline risk for ICH or ischemic stroke improved the incremental cost-effectiveness of high-dose dabigatran, compared with warfarin.

Our Critique

The economic analysis was well conducted with a full comparison of health care strategies, measurement of costs, and sensitivity analyses. The FDA approved only the 150-mg dose of dabigatran for use in the United States (and the 75-mg dose for patients with renal dysfunction) based upon their "inability to identify any subgroup in which use of the lower dose would not represent a substantial disadvantage." The investigators made the assumption that the cost of dabigatran would be $13.00 for the 150-mg bid dose. However, Boehringer Ingelheim has reportedly set the U.S. wholesale price of two 150-mg dabigatran capsules at $6.75, which would improve the cost-effectiveness values reported in the current study. Consideration needs to be given to other potentially challenging aspects of the clinical management of patients on dabigatran, including the need to understand how to assay for anticoagulation status in patients who have overdosed or need surgery – activated partial thromboplastin time and thrombin time seem to be the most reliable. No specific antidote is available to reverse the anticoagulant effect, but it has a shorter half-life than does warfarin (12-14 hours vs. 36-42 hours). As a direct thrombin inhibitor, reversal of the effects cannot be achieved with conventional therapy such as vitamin K or blood products. The ideal candidate has the demeanor of an "early adopter," has a fairly good grasp of the risks vs. the benefits, is not participating in high-risk activities that would include traumatic injury, has an active lifestyle, and has nonvalvular atrial fibrillation for which this drug is intended.

• Clinical Decision: You encourage the patient to contact his insurer and check into his prescription coverage or it will cost him about $675 for a 3-month course of therapy. He tells you he will consider paying for it on his own if it is not covered.

Cost Effectiveness of Dabigatran