Accountable care organizations (ACOs), in which providers are held accountable for the costs of treating a payer’s patent population, will become more the rule than the exception in a year, as providers and payers alike move to accommodate a new payment paradigm that shifts the focus away from pay for quantity to pay for quality and cost-effective care delivery. Acute coronary syndrome (ACS)—which encompasses myocardial infarction and unstable angina—and atrial fibrillation (AF)—the most common sustained arrhythmia—are two conditions that are ripe for ACO-related outcomes and cost improvements. In particular, AF is among the top conditions (along with chronic obstructive pulmonary disease and type 2 diabetes)—that managed care organizations believe represent the best opportunities for ACOs to make a difference for outcomes improvements and cost efficiencies in the ACO. The adoption of the ACO model is spreading from its origins in the Medicare system into the realm of commercial health plans. ACOs are making cardiologists more conscious of the long-term consequences of each prescribing decision by linking their reimbursement to the achievement of goals such as reducing hospital readmissions and total medical costs as well as saving on prescription drug costs. They are holding physicians accountable for reaching generic prescribing rates, which may conflict with the drugs cardiologists believe are the most effective course of treatment for the ACS and AF to reduce the occurrence of myocardial infarction and stroke. Although ACO monitoring of patient adherence to AF and ACS drugs may increase sales, the ACO focus on cost-cutting drives many of these additional sales to generic competitors of brand name drugs in classes such as antithrombotics, antiarrhythmics, anticoagulants, and antiplatelet agents. Cardiologists and MCOs alike note that ACOs are already driving an increase in prescribing for generic mainstays, clopidogrel for ACS and warfarin for AF, and resulting in a decrease of prescribing for Plavix and Coumadin. This environment is becoming more challenging for branded drugs that seek to compete: such as Eli Lilly’s Effient (prasugrel), AstraZeneca’s Brilinta (ticagrelor), Sanofi’s Multaq (dronedarone), and Pfizer/Bristol-Myers Squibb’s Eliquis (apixaban). Branded drug marketers can use a variety of means to protect market share in the challenging ACO environment, including highlighting clinical advantages that keep patients out of the hospital or help patients be more compliant with their therapies. For instance, the novel anticoagulants, such as Pradaxa, Xarelto, and Eliquis, have demonstrated some clinical advantages over warfarin in preventing strokes and venous thromboembolic events. Drug marketers should be prepared to point out any brand advantages that meet the ACO’s goals of increasing compliance, reducing hospital readmissions, and other health outcomes improvements. In addition, many brands might need to preserve their place in ACO formularies by discounting prices under contracts favorable to ACOs.