Moving the Tipping Point

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Abstract
Background— The rate of ischemic stroke associated with traditional risk factors for patients with atrial fibrillation has declined over the past 2 decades. Furthermore, new and potentially safer anticoagulants are on the horizon. Thus, the balance between risk factors for stroke and benefit of anticoagulation may be shifting. Methods and Results— The Markov state transition decision model was used to analyze the CHADS2 score, above which anticoagulation is preferred, first using the stroke rate predicted for the CHADS2 derivation cohort, and then using the stroke rate from the more contemporary AnTicoagulation and Risk Factors In Atrial Fibrillation cohort for any CHADS2 score. The base case was a 69-year-old man with atrial fibrillation. Interventions included oral anticoagulant therapy with warfarin or a hypothetical “new and safer” anticoagulant (based on dabigatran), no antithrombotic therapy, or aspirin. Warfarin is preferred above a stroke rate of 1.7% per year, whereas aspirin is preferred at lower rates of stroke. Anticoagulation with warfarin is preferred even for a score of 0 using the higher rates of the older CHADS2 derivation cohort. Using more contemporary and lower estimates of stroke risk raises the threshold for use of warfarin to a CHADS2 score ≥2. However, anticoagulation with a “new, safer” agent, modeled on the results of the Randomized Evaluation of Long-Term Anticoagulation Therapy trial of dabigatran, leads to a lowering of the threshold for anticoagulation to a stroke rate of 0.9% per year. Conclusions— Use of a more contemporary estimate of stroke risk shifts the “tipping point,” such that anticoagulation is preferred at a higher CHADS2 score, reducing the number of patients for whom anticoagulation is recommended. The introduction of “new, safer” agents, however, would shift the tipping point in the opposite direction.