Mintu P. Turakhia

Cost-Effectiveness of Dabigatran Compared With Warfarin for Stroke Prevention in Atrial Fibrillation

BACKGROUND Warfarin reduces the risk for ischemic stroke in patients with atrial fibrillation (AF) but increases the risk for hemorrhage. Dabigatran is a fixed-dose, oral direct thrombin inhibitor with similar or reduced rates of ischemic stroke and intracranial hemorrhage in patients with AF compared with those of warfarin. OBJECTIVE To estimate the quality-adjusted survival, costs, and cost-effectiveness of dabigatran compared with adjusted-dose warfarin for preventing ischemic stroke in patients 65 years or older with nonvalvular AF. DESIGN Markov decision model. DATA SOURCES The RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial and other published studies of anticoagulation. The cost of dabigatran was estimated on the basis of pricing in the United Kingdom. TARGET POPULATION Patients aged 65 years or older with nonvalvular AF and risk factors for stroke (CHADS₂ score ≥1 or equivalent) and no contraindications to anticoagulation. TIME HORIZON Lifetime. PERSPECTIVE Societal. INTERVENTION Warfarin anticoagulation (target international normalized ratio, 2.0 to 3.0); dabigatran, 110 mg twice daily (low dose); and dabigatran, 150 mg twice daily (high dose). OUTCOME MEASURES Quality-adjusted life-years (QALYs), costs (in 2008 U.S. dollars), and incremental cost-effectiveness ratios. RESULTS OF BASE-CASE ANALYSIS The quality-adjusted life expectancy was 10.28 QALYs with warfarin, 10.70 QALYs with low-dose dabigatran, and 10.84 QALYs with high-dose dabigatran. Total costs were

Oral antithrombotic agents for the prevention of stroke in nonvalvular atrial fibrillation: a science advisory for healthcare professionals from the American Heart Association/American Stroke Association.

143 193 for warfarin,

Early Repolarization in an Ambulatory Clinical Population

164 576 for low-dose dabigatran, and

Oral Anticoagulant Therapy Prescription in Patients With Atrial Fibrillation Across the Spectrum of Stroke Risk: Insights From the NCDR PINNACLE Registry

168 398 for high-dose dabigatran. The incremental cost-effectiveness ratios compared with warfarin were

Clinical InvestigationElectrophysiologyAdherence to dabigatran therapy and longitudinal patient outcomes: Insights from the Veterans Health Administration

51 229 per QALY for low-dose dabigatran and

Left Atrial Function Predicts Heart Failure Hospitalization in Subjects with Preserved Ejection Fraction and Coronary Heart Disease: Longitudinal Data from the Heart and Soul Study

45 372 per QALY for high-dose dabigatran. RESULTS OF SENSITIVITY ANALYSIS The model was sensitive to the cost of dabigatran but was relatively insensitive to other model inputs. The incremental cost-effectiveness ratio increased to

Screening for Atrial Fibrillation A Report of the AF-SCREEN International Collaboration

50 000 per QALY at a cost of

The CHADS2 score predicts ischemic stroke in the absence of atrial fibrillation among subjects with coronary heart disease: data from the Heart and Soul Study.

13.70 per day for high-dose dabigatran but remained less than

Site-Level Variation in and Practices Associated With Dabigatran Adherence

85 000 per QALY over the full range of model inputs evaluated. The cost-effectiveness of high-dose dabigatran improved with increasing risk for stroke and intracranial hemorrhage. LIMITATION Event rates were largely derived from a single randomized clinical trial and extrapolated to a 35-year time frame from clinical trials with approximately 2-year follow-up. CONCLUSION In patients aged 65 years or older with nonvalvular AF at increased risk for stroke (CHADS₂ score ≥1 or equivalent), dabigatran may be a cost-effective alternative to warfarin depending on pricing in the United States. PRIMARY FUNDING SOURCE American Heart Association and Veterans Affairs Health Services Research & Development Service.

Atrial Fibrillation Burden and Short-Term Risk of Stroke: Case-Crossover Analysis of Continuously Recorded Heart Rhythm From Cardiac Electronic Implanted Devices

The rate of stroke among adults with atrial fibrillation (AF) varies widely, ranging between 1% and 20% annually (mean 4.5% per year) depending on comorbidities and a patient’s history of prior cerebrovascular events.1 Stratification of stroke risk is important, because the major risk of antithrombotic medications used to lower the incidence of AF-related stroke is bleeding. For warfarin, this involves balancing a bleeding risk of 1% to 12% per year against the risk of ischemic events, with its use generally reserved for individuals at greatest thromboembolic risk.1–3 The advent of several new antithrombotic agents offers alternatives to warfarin and may lower the threshold for thromboembolic risk for initiating therapy in patients with AF. In this update to the American Heart Association/American Stroke Association (AHA/ASA) “Guidelines for the Primary Prevention of Stroke”4 and the prevention of stroke in patients with stroke or transient ischemic attack (TIA),5 we review recent trials testing the safety and efficacy of a thrombin inhibitor (dabigatran) and 2 factor Xa inhibitors (rivaroxaban and apixaban) in preventing stroke in patients with AF, and we revise management recommendations.4,5 Recommendations follow the AHA’s and the American College of Cardiology’s methods of classifying the level of certainty of the treatment effect and the class of evidence (Table 1). View this table: Table 1. Applying Classification of Recommendations and Level of Evidence ### Risk Stratification The absolute risk of stroke varies 20-fold among AF patients according to age and associated vascular comorbidities. Several stroke risk stratification schemes have been developed and validated.6–8 These, however, can yield differing results.9 Current AHA guidelines use the CHADS2 stratification scheme7 (CHADS2 is an acronym for Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, and prior Stroke or TIA). The CHADS2 score was derived from independent …