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The search for a safer and more tolerable anticoagulant alternative to warfarin has been the holy grail of thromboembolic research for decades. With its capacity to reduce the risk of ischemic stroke by nearly two thirds in patients with atrial fibrillation, warfarin remains one of the most powerful preventive tools in all of medicine.1 But in the 57 years since the drug was introduced, generations of clinicians and patients have become all too familiar with the difficulty of establishing and maintaining an adequate level of the international normalized ratio (INR) in the face of intercurrent illnesses, the use of myriad interacting drugs, and dietary changes. Partly as a result, anticoagulation remains woefully underused in patients for whom it could do enormous good.2 Sensitive to problems that result from commission more than from omission, physicians often overestimate the likelihood of hemorrhagic complications and underestimate the consequences of failing to prevent embolic events.3Article see p 2562This is especially true in older patients, whom prescribers excessively perceive to be poor risks for anticoagulation, because they are frail or more likely to fall—even though these are the very patients at highest risk for preventable atrial fibrillation-induced stroke.4 Although there is good evidence that well-run anticoagulation clinics can help patients to hit the sweet spot of an INR of 2 to 3 consistently, most receive warfarin without benefit of such services. As a result, the average patient prescribed warfarin spends a distressingly high proportion of time either over or under the safe INR range. The prospect that pharmacogenetic testing could guide warfarin dosing, although now enshrined in the official labeling for the drug, has not been borne out as a compelling clinical or economic strategy.5The search for a better alternative to warfarin has had several false starts …

The Relative Cost-Effectiveness of Anticoagulants