Dabigatran Cost-Effective Only for A-Fib Patients at High Stroke Risk

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For most atrial fibrillation (A-fib) patients at high risk of stroke, the reversible, direct thrombin inhibitor dabigatran is a cost-effective alternative to warfarin, according to a study published online May 23, 2011, ahead of print in Circulation. However, the analysis found that in patients at low or moderate risk of stroke, aspirin or warfarin were the more cost-effective options.

Shimoli V. Shah, MD, and Brian F. Gage, MD, MSc, both of Washington University School of Medicine (St. Louis, MO), conducted a cost analysis of prophylactic therapies based on data from RE-LY (Randomized Evaluation of Long Term Anticoagulation Therapy) and other trials. The RE-LY trial (Connolly SJ, et al. N Engl J Med. 2009;361:1139-1151) compared 2 doses of dabigatran (110 or 150 mg twice daily) with warfarin (adjusted dose) in 18,113 patients who were at risk of stroke from nonvalvular A-fib, demonstrating similar or better effectiveness with the newer agent in preventing stroke and systemic embolism, with equal or lower risk of major bleeding.

For the new analysis, the annual cost of warfarin, which included Medicare reimbursement rates for 14 monitoring tests and office visits, was estimated at $545 ($1.50 per day), clopidogrel at $1,847 ($5.06 per day) and dabigatran at $3,240 ($9 per day). In a model that incorporated a hypothetical cohort of 70-year-old patients with A-fib, the researchers used a cost-effectiveness threshold of $50,000 per quality-adjusted life-year. Stroke risk was estimated using the CHADS2 score, which takes into account congestive heart failure, hypertension, age ≥ 75, diabetes, and prior stroke or TIA.

Cost-Effectiveness Depends on Stroke Risk

For a patient with an average risk of major hemorrhage (approximately 3% per year), the most cost-effective therapy depended on stroke risk:

• For patients with the lowest stroke risk (CHADS2 score of 0), aspirin was cost-effective
• For patients with moderate stroke risk (CHADS2 score of 1 or 2), warfarin was cost-effective unless the risk of hemorrhage was high or the quality of international normalized ratio (INR) control was poor
• For patients with high stroke risk (CHADS2 score ≥ 3), dabigatran 150 mg was cost-effective unless INR control was excellent

The incidence of major bleeding did not have a significant effect on cost-effectiveness such that dabigatran 150 mg was cost-effective at a CHADS2 score of ≥ 3 regardless of hemorrhage risk, and at a CHADS2 score of 2 if the risk of major bleeding was high. However, aspirin was the only cost-effective therapy at a CHADS2 score of 0 unless the risk of major bleeding was high, in which case no antithrombotic therapy was cost-effective. Warfarin was cost-effective at a CHADS2 score of 1 or 2 with low major bleeding rates.

Because of the greater efficacy of dabigatran 150 mg, dabigatran 110 mg was not cost-effective for any realistic rate of stroke and hemorrhage. Likewise, dual therapy (aspirin and clopidogrel) was not cost effective.

RE-LY vs. the Real World

In an editorial accompanying the study, Jerry Avorn, MD, of Harvard Medical School (Boston, MA), writes that one advantage of the current analysis over previous work on this question “is that [the authors] go on to rigorously do what good physicians intuitively do all the time: they stratify patients in terms of their risks to determine the most appropriate regimens for different groups.”

Furthermore, Dr. Avorn contends that “[w]hereas the RE-LY trial concluded that overall, dabigatran 150 mg BID conferred greater stroke protection than warfarin at comparable bleeding risk, and a prior study concluded that it was likely to be more cost-effective, [the new analysis] takes the assessment to a more detailed level in also considering preexisting risk of hemorrhage, stroke risk, and likelihood of adequate INR control.”

But he cautions that “a key next step will be to see how dabigatran fares in the bumpy, messier setting of typical patient care, where it may perform differently than RE-LY would suggest.”

“For many of those with atrial fibrillation, over time [dabigatran] may prove to be a safer alternative to warfarin, even if its economic value in this comparison has yet to be measured adequately,” Dr. Avorn writes. “But for many other patients, until we know more about its track record in this more demanding but far more relevant setting, there is merit to the recent joint professional society recommendation of the American College of Cardiology and the American Heart Association that for those who are currently stable and doing well on warfarin until we learn more, staying the course with that annoying old standby may be a prudent—and certainly affordable— course of action for the near future for many other patients.”

The study authors caution against being “tempted to prescribe dabigatran even when it would not be cost-effective” and point out the higher rate of dyspepsia and possible MIs with dabigatran as well as the 12- to 17-hour half-life, which could make lapses on dabigatran therapy more problematic than lapses on warfarin.

Underestimating the ‘Costs’ of Warfarin

But Joshua Z. Willey, MD, of Columbia University Medical Center (New York, NY), said the analysis makes assumptions that may underestimate the cost of hemorrhagic care, which could mean dabigatran may be more cost-effective in the long run. In addition, while the study authors give an estimate of 14 visits per year to monitor INR on warfarin, Dr. Willey says many of his patients actually require as many as 40 visits.

“I think it’s good to have these cost-effectiveness data because so often you have patients who, despite our best attempts and theirs, cannot get their INR under control and so this analysis tells us dabigatran would be more cost-effective for those patients,” Dr. Willey said. He added that emerging evidence on genetic markers that could identify patients who will not do well on warfarin is another reason cost-effectiveness data for dabigatran may be useful.

“The cost is an overwhelming barrier for many of us,” Dr. Willey said. “Hopefully cost-effectiveness data such as these will change how insurance companies are covering this type of medication because most of us who prescribe it feel that this is an appropriate medication for most of our A-fib patients.”

Dr. Willey added that one ‘cost’ that analyses such as this cannot measure is the impact of treatment on patients’ overall satisfaction.

“It seems like a small thing, but many of my patients are so happy once they go on dabigatran because they can eat green vegetables again,” he said. “The severe dietary restrictions with warfarin are a problem. We talk about quality-adjusted life years, but you have to think also in terms of the overall quality of life of your patient.”

 

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Sources:
1. Shah SV, Gage BF. Cost-effectiveness of dabigatran for stroke prophylaxis in atrial fibrillation. Circulation. 2011;123:2562-2570.

2. Avorn J. The relative cost-effectiveness of anticoagulants: Obvious, except for the cost and the effectiveness. Circulation. 2011;123:2519-2521.

 

 

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