Circ: 150mg of Pradaxa cost-effective, but only when indicated

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Dabigatran etexilate (Pradaxa, Boehringer Ingelheim), a drug approved for stroke prevention in non-valvular atrial fibrillation (AF) patients, provides the first antithrombotic alternative to warfarin, but is it cost-effective? A study published June 7 in Circulation found that the 150 mg dose of dabigatran was cost-effective in high-risk AF populations, unless however international normalized ratio (INR) control with warfarin was excellent.

In October 2010, the FDA approved the 150 mg dose of dabigatran after the results of the RE-LY trial, which compared dabigatran and warfarin, showed that dabigatran was superior in terms of stroke prevention. However, controversy has stemmed from the fact that the lower 110 mg dose of dabigatran was not approved due to the heightened risk of bleeding associated with the drug.

“Traditional antithrombotic therapies for AF are not ideal,” wrote Shimoli V. Shah, MD, of the Washington University in St. Louis, and colleagues. For example, a 325 mg dose of aspirin only reduces the risk of ischemic stroke by 22 percent.

Likewise, warfarin may reduce the risk of stroke by 64 percent, but it also increases the risk of major bleeding by 69 percent. Warfarin also has a narrow therapeutic range, creates multiple food and drug interactions and requires regular monitoring. Dabigatran's approval may help address the pitfalls of warfarin.

To gain insight into the costs associated with dabigatran, Shah et al used a Markov model to compare costs with quality-adjusted survival of antithrombotic therapies. The researchers used a hypothetical cohort of AF patients who were 70 years old, had no contraindications to anticoagulant therapy and had a mild risk of stroke. The cost-effectiveness threshold used was $50,000/quality-adjusted life years (QALYs).

The researchers compared the survival and costs of: 110 mg or 150 mg twice daily doses of dabigatran, warfarin, dual therapy with aspirin and clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis), aspirin alone or no antithrombotic therapy.

Shah and colleagues estimated the cost of dabigatran to be $9 per day.

During the study, warfarin was estimated to cost nearly $12,000 per QALY compared with aspirin. The 150 mg dose of dabigatran was linked to the greatest quality-adjusted survival--8.65 QALYs. The 110 mg twice daily dose of dabigatran was associated with 8.54 QALYs followed by warfarin with 8.40 QALYs and aspirin with 8.17 QALYs.

The 150 mg dose of dabigatran was more cost-effective—$86,000 per QALY—than 110 mgs of dabigatran or dual therapy (aspirin and clopidogrel). Shah and colleagues hypothetically extended dabigatran use from 20 to 40 years and found that 150 mg of dabigatran would cost $84,000 per QALY versus warfarin.

While warfarin was most cost-effective for patients at a moderate risk of stroke (CHADS2 of 1 or 2), dabigatran 150 mg was most cost-effective for patients with a CHADS2 score of 2 if risk of hemorrhage was more than 6 percent per year or lower hemorrhage rates if costs were less than $2,500 per year.

Dabigatran 150 mg was most cost-effective for high-risk patients with a CHADS2 score of 3 or greater, irrespective of hemorrhage rates. In this same situation, dabigatran 110 mg and dual therapy was not cost-effective. The researchers found that major bleeding rate had less effect on cost-effectiveness.

“Cost-effectiveness of dabigatran 150 mg was sensitive to its price: If dabigatran 150 mg costs less than $1,800/y, it was always more cost-effective than warfarin (regardless of stroke and hemorrhage rates),” the authors wrote.

“Because of the greater efficacy of dabigatran 150 mg, dabigatran 110 mg (also twice daily) was not cost-effective for any realistic rate of stroke and hemorrhage. Likewise, dual [antiplatelet] therapy (aspirin and clopidogrel) was never cost-effective,” the authors noted.

Shah et al suggested that genetic testing could guide therapy in situations where hemorrhage risk determines the most cost-effective therapy. Patients with CYP2C9 alleles metabolize warfarin slower and have triple the risk of hemorrhage after warfarin initiation.

“If a patient with a CHADS2 score of 2 and moderate risk of hemorrhage is found to be a slow metabolizer of warfarin, then the hemorrhage risk is greater and dabigatran could become cost-effective. However, if genotyping continues to cost more than $200, it is unlikely to be cost-effective for AF populations.

“In summary, the benefits of dabigatran outweigh costs in AF patients at moderate to high risk of stroke and/or hemorrhage unless their INR control with warfarin therapy would be excellent,” the authors concluded. However, they said that clinicians may want to prescribe dabigatran even when it would not be cost-effective, this would increase costs with only modest health benefits.

Dabigatran caused more incidence of dyspepsia and more MIs than warfarin in the RE-LY trial. The researchers cautioned that prescribing dabigatran when it is not indicated for use has the potential to worsen health.