The Canadian journal of cardiology
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Warfarin has been the mainstay oral anticoagulant (OAC) medication prescribed for stroke prevention in atrial fibrillation (AF) patients. However, warfarin therapy is challenging because of marked interindividual variability in dose and response, requiring frequent monitoring and dose titration. These limitations have prompted the clinical development of new OACs (NOACs) that directly target the coagulation cascade with rapid onset/offset of action, lower risk for drug-drug interactions, and more predictable response. ⋯ Though the anticoagulation efficacy of these NOACs has been characterized, differences in their pharmacokinetic and pharmacodynamic profiles have become a significant consideration in terms of drug selection and dosing. In this review, we outline key pharmacokinetic and pharmacodynamic features of each compound and provide guidance on selection and dosing of the 3 NOACs relative to warfarin when considering OAC therapy for AF patients. Importantly, we show that by better understanding the effect of clinical variables such as age, renal function, dosing interval, and drug metabolism (CYP3A4) and transport (P-glycoprotein), we might be able to better predict the risk for sub- and supratherapeutic anticoagulation response and individualize OAC selection and dosing.
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Fontan surgery represents a milestone in the evolution of congenital heart disease management. It achieved the seemingly improbable (ie, restoration of a noncyanotic state by entirely bypassing the subpulmonary ventricle). In so doing, it has allowed a generation of children who may have otherwise succumbed to their severe congenital heart defect to survive to adulthood. ⋯ Continued research in therapies is needed for univentricular dysfunction and systemic complications of Fontan palliation, including potential uses of mechanical support as a bridge to transplantation or as a neosubpulmonary ventricle. Fontan patients remain a major challenge to the medical and surgical community as a whole. Multicentre and multidisciplinary efforts to improve the density and depth of experiences might lead to a better appreciation for, and management of, Fontan failure and its ramifications.
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Warfarin is effective for the prevention and treatment of thromboembolism but produces variable anticoagulant effects and requires routine monitoring of the international normalized ratio (INR) to optimize the balance between efficacy and safety. The new oral anticoagulants (NOACs) have a more predictable anticoagulant effect and were recently demonstrated to be at least as efficacious and safe as warfarin despite being administered in fixed doses without routine coagulation monitoring. Specific laboratory tests have been developed to measure the anticoagulant effect of the NOACs but are not yet widely available, and the relation between drug levels and both coagulation test results and outcomes is uncertain. ⋯ In patients with major or life-threatening bleeding and those requiring surgery, the anticoagulant effects of warfarin can be reversed using oral or intravenous vitamin K, fresh frozen plasma (FFP), and prothrombin complex concentrates (PCCs). Specific antidotes are under development for the NOACs but are not yet approved for clinical use. PCCs and recombinant factor VIIa may improve hemostasis in patients in whom bleeding develops during treatment with a NOAC, but their efficacy is unproven.
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Randomized controlled trials have demonstrated benefits from antithrombotic therapies for coronary artery disease (primary prevention, stable coronary artery disease, acute coronary syndromes, and percutaneous intervention) and for atrial fibrillation. The regimens with the optimal balance of efficacy and safety with coronary artery disease depend on the particular clinical manifestation, with atrial fibrillation on the risk of stroke, and with both conditions on the competing risk of major bleeding with the chosen antithrombotic therapy. ⋯ Practice guidelines now recommend oral anticoagulant therapy for most patients with atrial fibrillation and consideration of "triple therapy" (oral anticoagulant and aspirin and clopidogrel) when there is a concomitant acute coronary syndrome or stent placement, though acknowledging the risks of major bleeding. In the absence of definitive trials of combination therapies, such practice guidelines are based on extrapolations from randomized trials and observational data.
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A growing number of patients with atrial fibrillation are treated with oral anticoagulation (OAC), and a large proportion of them will require surgical or other invasive procedures. These procedures typically involve interruption of OAC with or without the use of heparin bridging; however; there has been a dramatic change in this practice during the past 3 years. The introduction of short-acting, new oral anticoagulants and the growing popularity of some low-risk procedures with continued OAC have transformed our practice. Physicians and surgeons who treat patients with atrial fibrillation must be aware of these changes and understand how to deal with the new challenges they may encounter.