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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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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The term "silent" atrial fibrillation (AF) has recently re-emerged to describe atrial arrhythmias that are detected by implanted cardiac devices but would generally go undetected in the clinical setting. The precise role that silent AF plays in increasing the risk of ischemic stroke is not fully understood. The purpose of this article is to: (1) review the current evidence demonstrating that silent AF is associated with thromboembolic events; (2) describe the temporal proximity of silent AF episodes to thromboembolic events; (3) present data on the incidence of newly detected silent AF in patients without a previous history of AF; and (4) provide an overview of ongoing and new clinical studies on this important topic. ⋯ The AF burden threshold which confers this increased thromboembolism risk is not precisely defined, but might be as brief as several minutes to several hours. The advent of novel oral anticoagulation medications, which offer the promise of improved efficacy along with superior safety profiles, might warrant more aggressive identification of patients who might benefit from these therapies. However, to find high risk patients who have brief episodes of silent AF will likely require new methods of monitoring to permit the detection of this elusive but potentially dangerous arrhythmia.
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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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Comparative Study
Incidence and significance of pericardial effusion in patients with pulmonary arterial hypertension.
The incidence of pericardial effusion (PEF) during long-term follow-up among patients with pulmonary arterial hypertension (PAH) is unknown. We aimed to determine the incidence and prognostic significance of developing a new PEF among PAH patients. ⋯ PEF develops frequently in PAH patients. In patients with no PEF at baseline, the appearance of a new moderate-size or larger PEF is associated with increased mortality, whereas no significantly increased mortality was observed when a small PEF develops.