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Objective: To compare key features of the new oral anticoagulants (NOACs)-dabigatran, rivaroxaban, and apixaban-and to address questions that arise when comparing the NOACs., Sources of Information: PubMed was searched for recent (January 2008 to week 32 of 2013) clinical studies relating to NOAC use for stroke prevention in atrial fibrillation (AF) and for the treatment of acute venous thromboembolism (VTE)., Main Message: All NOACs are at least as effective as warfarin for stroke prevention in patients with nonvalvular AF, and are at least as safe in terms of bleeding risk according to 3 large trials. Meta-analyses of these trials have shown that, compared with warfarin therapy, NOACs reduced total mortality, cardiovascular mortality, and intracranial bleeding, and there was a trend toward less overall bleeding. Practical advantages of NOACs over warfarin include fixed once- or twice-daily oral dosing without the need for coagulation monitoring, and few known or defined drug or food interactions. Potential drawbacks of NOACs include a risk of bleeding that might be increased in patients older than 75 years, increased major gastrointestinal bleeding with high-dose dabigatran, increased dyspepsia with dabigatran, the lack of a routine laboratory test to reliably measure anticoagulant effect, and the lack of an antidote for reversal. No direct comparisons of NOACs have been made in randomized controlled trials, and the choice of NOAC is influenced by individual patient characteristics, including risk of stroke or VTE, risk of bleeding, and comorbidity (eg, renal dysfunction)., Conclusion: The NOACs represent important alternatives in the management of patients with AF and VTE, especially for patients who have difficulty accessing regular coagulation monitoring. The companion to this article addresses common "what if" questions that arise in the long-term clinical follow-up and management of patients receiving NOACs., (Copyright© the College of Family Physicians of Canada.)

Objective: To address common "what if" questions that arise relating to the long-term clinical follow-up and management of patients receiving the new oral anticoagulants (NOACs)., Sources of Information: For this narrative review, we searched the PubMed database for recent (January 2008 to week 32 of 2013) clinical studies relating to NOAC use for stroke prevention in atrial fibrillation and for the treatment of acute venous thromboembolism. We used this evidence base to address prespecified questions relating to NOAC use in primary care settings., Main Message: Dabigatran and rivaroxaban should be taken with meals to decrease dyspepsia and increase absorption, respectively. There are no dietary restrictions with any of the NOACs, beyond moderating alcohol intake, and rivaroxaban and apixaban can be crushed if required. The use of acid suppressive therapies does not appear to affect the efficacy of the NOACs. As with warfarin, patients taking NOACs should avoid long-term use of nonsteroidal anti-inflammatory and antiplatelet drugs. For patients requiring surgery, generally NOACs should be stopped 2 to 5 days before the procedure, depending on bleeding risk, and the NOAC should usually be resumed at least 24 hours after surgery. Preoperative coagulation testing is generally unnecessary. In patients who develop bleeding, minor bleeding typically does not require laboratory testing or discontinuation of NOACs; with major bleeding, the focus should be on local measures to control the bleeding and supportive care, and coagulation testing should be performed. There are currently no antidotes to reverse NOACs. The NOACs should not be used in patients with valvular heart disease, prosthetic heart valves, cancer-associated deep vein thrombosis, or superficial thrombophlebitis., Conclusion: Management of "what if" scenarios for patients taking NOACs have been proposed, but additional study is needed to address these issues, especially periprocedural management and bleeding., (Copyright© the College of Family Physicians of Canada.)

Background and Purpose: Heart failure is an independent risk factor for stroke. Anticoagulation is effective for prevention of cardio-embolic stroke secondary to atrial fibrillation or mechanical heart valves but is of uncertain benefit in heart failure patients. We performed this meta-analysis to obtain the best estimates of the efficacy and safety of warfarin as compared with antiplatelet therapy in patients with systolic heart failure who are in sinus rhythm., Methods and Results: A systematic search was performed using PubMed and Central Register of Controlled Trials databases for all randomized controlled trials, which compare warfarin with antiplatelet therapy given for at least one-month in heart failure patients with sinus rhythm and report at least one of the following outcomes: ischemic stroke, death, myocardial infarction, hospitalization due to worsening heart failure, intracranial hemorrhage, and major hemorrhage. Four randomized controlled trials involving adjusted-dose warfarin (4187 subjects) were included. When compared with antiplatelet therapy, warfarin reduced ischemic stroke by 0·74% per year (RR 0·49; 95% CI: 0·32-0·73: P = 0·0006; Number needed to treat = 135) but increased major hemorrhage by 0·99% per year (RR 2·15; 95% CI: 1·55-2·99: P < 0·00001; Number needed to harm = 101). Warfarin did not significantly affect the risk of death, myocardial infarction, hospitalization due to heart failure or intracranial hemorrhage as compared with antiplatelet therapy., Conclusions: Warfarin as compared with antiplatelet therapy reduces risk of ischemic stroke, does not significantly affect death, myocardial infarction, hospitalization due to heart failure or intracranial hemorrhage and increases major hemorrhage in heart failure patients who are in sinus rhythm., (© 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.)

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. It remains to be demonstrated whether adjustment of the dose of NOACs, according to the results of laboratory testing, may lead to even greater efficacy and safety. The principles of bleeding management in patients treated with NOACs compared with patients receiving warfarin are similar. Most patients can be safely managed by interrupting drug treatment, performing local measures to stem the bleeding, and providing transfusion support as required. 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., (Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Deep venous thrombosis (DVT) is common and associated with significant morbidity and mortality if not diagnosed early and managed effectively. Specific conditions including advanced age, obesity and renal impairment need to be considered when implementing anticoagulation treatment to ensure optimal therapeutic efficacy and safety., Areas Covered: This review summarizes the current treatment of acute DVT according to the 2012 American College of Physicians Evidence-based Clinical Practice Guidelines. Recent and ongoing clinical trials on acute DVT treatment are highlighted. The authors also provide suggestion for the treatment of DVT in patients with advanced age, obesity and renal impairment., Expert Opinion: New oral anticoagulants (NOACs) have the potential as an alternative to warfarin for DVT treatment. Elastic compressive stockings and catheter-directed thrombolysis should be considered for symptomatic relief and the prevention of post-thrombotic syndrome, respectively. ASA has emerged as a treatment option for selected patients with unprovoked DVT and pulmonary embolism (PE) with a low-to-intermediate risk for disease recurrence or who are unsuitable for long-term oral anticoagulant therapy due to practical or safety reasons. Additional trials are needed in special patient populations, including the elderly, obese and those with renal impairment and cancer-associated DVT, to assess the efficacy and safety of anticoagulants especially the NOACs for DVT treatment.

The novel oral anticoagulant drugs, comprising dabigatran, rivaroxaban, and apixaban, have emerged as compelling alternatives to vitamin K antagonists for stroke prevention in atrial fibrillation, and low‑molecular‑weight heparin for thromboprophylaxis following hip and knee arthroplasty. Rivaroxaban has also been approved for treatment of venous thromboembolism. However, the role of these drugs for the management of patients with an acute coronary syndrome (ACS) is less certain. The purpose of this review was to summarize the randomized trials evaluating novel oral anticoagulants in patients with an ACS and consider the reasons why these drugs have not been incorporated into routine clinical practice. In addition, the situation involving rivaroxaban, which has been approved for use in patients with an acute coronary syndrome in Europe but not in North America, is discussed.

Purpose of Review: The prevalence of atrial fibrillation is increasing because of an aging population. Vitamin K antagonists have been the standard therapy for stroke prevention in atrial fibrillation but are underutilized and often poorly managed because of their inherent limitations. This study critically reviews the recently completed phase 3 randomized controlled trials of new oral anticoagulants (OACs) for stroke prevention in patients with nonvalvular atrial fibrillation: RE-LY (dabigatran), AVERROES (apixaban), ARISTOTLE (apixaban) and ROCKET-AF (rivaroxaban)., Recent Findings: On the basis of their favorable pharmacological characteristics and excellent efficacy and safety profile as demonstrated by the results of the randomized controlled trials, the new OACs have the potential to replace vitamin K antagonists as the first-line treatment for stroke prevention in atrial fibrillation, with warfarin reserved for patients with contraindications to the new OACs and those unable to afford them., Summary: The new OACs represent a major advance for patients with atrial fibrillation with the potential to reduce morbidity and mortality due to cardioembolic stroke.