Practical Considerations in the Use of Novel Oral Anticoagulants for Stroke Prevention in Nonvalvular Atrial Fibrillation

Atrial fibrillation (AF) is a highly prevalent cardiac arrhythmia associated with an increased risk of stroke. The role of anticoagulation therapy in the prevention of thrombosis and stroke is of critical importance for patients with AF. Limitations with vitamin K antagonists (VKAs), the current standard of care, have led to the development of novel oral anticoagulants (NOACs) that target either thrombin (dabigatran etexilate) or activated factor X (rivaroxaban, apixaban, and edoxaban). In comparison with traditional VKAs such as warfarin, these NOACs offer several pharmacologic advantages, including rapid onset of action, no significant food interactions, low potential for drug–drug interactions, and no requirement for routine coagulation monitoring. Completed phase‐III clinical trials have demonstrated the therapeutic potential of dabigatran, rivaroxaban, and apixaban in comparison with warfarin for stroke prevention in patients with nonvalvular AF (NVAF). While the future utility of NOACs in preventing stroke in patients with NVAF looks promising, several practical issues, including the current lack of a reversal strategy and use of these agents in older patients with renal dysfunction, must be considered. Clinician and patient understanding of such issues will be important for the safe and effective use of NOACs.     

Balancing Efficacy and Bleeding Risk in the Prevention of Stroke Due to Atrial Fibrillation with Newer Oral Anticoagulants

With the evaluation and approval of newer oral anticoagulants such as the factor IIa inhibitor, dabigatran etexilate and the factor Xa inhibitors, rivaroxaban and apixaban, strategies for stroke prevention in atrial fibrillation need a thorough re-evaluation of current options. Clinicians are naturally excited about the imminent introduction of these newer drugs that do not need international normalized ratio (INR) monitoring, besides having no drug–food and minimal drug–drug interactions. However, as with all new drugs, it is always prudent to use these judiciously so that they stay in our therapeutic armamentarium for a long time. More than 56 years after the introduction of warfarin we now have three drugs, viz., dabigatran 150 mg bid, rivaroxaban 20 mg od, and apixaban 5 mg bid which were effective in comparison with warfarin in reducing the risk of stroke and bleeding in the landmark trials, RE-LY, ROCKET-AF, and ARISTOTLE respectively. There is a thin dividing line between physiological hemostasis and pathological thrombosis. Routine INR monitoring may not be required but in special situations, such as prior to major surgery, overdose, non-compliance or stroke while on the anticoagulant, one may wish to know whether there are any laboratory measures of efficacy or means of reversal of over anticoagulation. Similar questions may be raised about other situations such as renal dysfunction, cardioversion, ablation procedures, post-stenting, or switch to and from warfarin, heparin or LMWH? This document is an attempt to address these concerns based on available evidence and give physicians a perspective and practice guidelines on how best to use these agents, both old and new, for optimal patient outcomes, maximizing efficacy and minimizing risk.     

Efficacy and Safety of Oral Anticoagulants in Patients With Atrial Fibrillation and Stages 4 or 5 Chronic Kidney Disease

PurposeThe aim of this study was to investigate whether oral anticoagulants can provide efficacy and safety profiles better than no anticoagulant in patients with stages 4 or 5 chronic kidney disease and atrial fibrillation.MethodsFrom 2001 to 2017, a cohort of patients with stages 4 or 5 chronic kidney disease and atrial fibrillation based on electronic medical records were selected from Chang Gung Memorial Hospital system in Taiwan. Patients were divided into nonvitamin K antagonist oral anticoagulants (NOACs), warfarin, and nonanticoagulated groups. They were followed from the index date to the occurrence of the study outcomes or for 5 years, whichever occurred first. The outcomes were admissions due to ischemic stroke or systemic embolism or major bleedings. Survival analyses were conducted to estimate the incidence rates of outcomes.ResultsA total of 3771 patients with atrial fibrillation and estimated glomerular filtration rate less than 30 mL/min/1.73m² were enrolled, of whom 2971 were in the nonanticoagulated group, 280 in the NOAC group, and 520 in the warfarin group. About 25% of all subjects (940 patients) were on dialysis. The mean follow-up was 3.2 years. After adjusting for sex, age, comorbidities, and comedication, the warfarin group had a significantly higher risk of ischemic stroke or systemic embolism (adjusted hazard ratio [aHR] 3.1, 95% confidence interval [CI] 2.1-4.6) than the nonanticoagulated group. The NOAC group had a similar risk of ischemic stroke or systemic embolism (aHR 1.1; 95% CI 0.3-3.4) to that of the nonanticoagulated group. Both the warfarin and the NOAC groups had a significantly higher major bleeding risk than the noncoagulated group (aHR 2.8 [95% CI 2.0-3.8] for warfarin; aHR 3.1 [95% CI 1.9-5.2] for NOAC).ConclusionThe use of NOACs or warfarin is not more effective than using no anticoagulants at all in reducing the risk of ischemic stroke or systemic embolism. Both NOACs and warfarin are associated with increased risk of major bleeding. Our results do not support the use of anticoagulants in patients with atrial fibrillation and stages 4-5 chronic kidney disease.     

Direct Oral Anticoagulants Versus Vitamin K Antagonists in Real-life Patients With Atrial Fibrillation. A Systematic Review and Meta-analysis

Introduction and objectives

To assess the effectiveness of direct oral anticoagulants vs vitamin K antagonists in real-life patients with atrial fibrillation.