Resuming Anticoagulation following Upper Gastrointestinal Bleeding among Patients with Nonvalvular Atrial Fibrillation�A Microsimulation Analysis

BACKGROUND Among patients with nonvalvular atrial fibrillation (NVAF) who have sustained an upper gastrointestinal bleed (UGIB), the benefits and harms of oral anticoagulation change over time. Early resumption of anticoagulation increases recurrent bleeding, while delayed resumption exposes patients to a higher risk of ischemic stroke. We therefore set out to estimate the expected benefit of resuming anticoagulation as a function of time after UGIB among patients with NVAF. METHODS We created a decision-analytic model estimating discounted quality-adjusted life-years when patients with NVAF resume anticoagulation on each day following UGIB. We simulated from a health system perspective over a lifelong time horizon. RESULTS Peak utility for warfarin was achieved by resumption 41 days after hemostasis from the index UGIB. Resumption between days 32 and 51 produced greater than 99.9% of the peak utility. Peak utility for apixaban was achieved by resumption 32 days after the index UGIB. Resumption between days 21 and 47 produced greater than 99.9% of the peak utility. Of input parameters, results were most sensitive to underlying stroke risk. Specifically, across the range of CHA2DS2-Vasc scores, the optimal day of resumption varied by around 11 days for patients resuming warfarin and by around 15 days for patients resuming apixaban. Results were less sensitive to underlying risk of rebleeding. CONCLUSIONS For patients with NVAF following UGIB, warfarin is optimally restarted approximately six weeks following hemostasis, and apixaban is optimally restarted approximately one month following hemostasis. Modest changes to this timing based on probability of thromboembolic stroke are reasonable.