Much of the difference between the groups could be attributed to a reduction in ICH in the apixaban group (0.24%/y versus 0.47%/y); the differ- ences in ischemic or uncertain type of stroke were minimal (0.97%/y versus 1.05%/y). Major bleeding events were simi- larly less frequent on apixaban (2.13%/y versus 3.09%/y; found a similar magnitude effect for primary prevention of stroke or systemic embolism in subjects without prior stroke or TIA the sharpest difference again in risk of ICH (0.29%/y versus analysis found consistent efficacy of apixaban in subjects with impaired renal function (estimated glomerular filtra- tion rate <80 mL/min) and significantly greater reduction in major bleeding among those with more advanced dysfunction (estimated glomerular filtration rate 50 mL/min).405 Because of the clustering of stroke observed after discontinuation of apixaban, a black box warning was required for this agent (as for rivaroxaban), indicating that coverage with another antico- agulant should be strongly considered at the time of cessation unless there is pathological bleeding. suggest that the newer oral anticoagu- lants can be cost-effective, particularly for patients at high risk of cardioembolism or hemorrhage. A Markov decision model using data from RE-LY, for example, found that dabigatran 150 mg twice daily provided 0.36 additional quality-adjusted life-years at a cost of $9000,407 representing an incremental cost-effectiveness ratio ($25000 per quality-adjusted life-year) that is within the range tolerated by many healthcare systems. These analyses are based on only a single trial of dabigatran, however, and similar evaluations have yet to be performed for rivaroxaban and apixaban. The cost-effectiveness of newer anticoagulants relative to adjusted-dose warfarin is predicted to be sensitive to the cost of the medications, the risk for cardio- embolism or hemorrhage (cost-effectiveness improving with increasing risk), and the quality of INR control on warfarin. 