How we treat bleeding associated with direct oral anticoagulants

Direct oral anticoagulants are at least as effective as vitamin K antagonists for the prevention and treatment of thromboembolism. Unfortunately, differently from vitamin K antagonists, they have the great drawback of lacking specific antidotes in the case of bleeding or emergency situations such as trauma, stroke requiring thrombolysis, and urgent surgery. The progressive development of antidotes for these new drugs, which, it is hoped, will become available in the near future, will allow better and safer management of the rapid reversal of their anticoagulant effect

New oral anticoagulants and their reversal agents

Atrial fibrillation is a commonly encountered pathology in medical practice, and its prevalence has shown a continuous rise over the past years. Atrial fibrillation has a significant impact on patients\u27 quality of life, not only due to the standard anticoagulant treatment with vitamin K antagonists that require close monitoring and dose adjustment, but also due to the fragile equilibrium between hemorrhagic and thrombotic risks. The introduction of new oral anticoagulants (NOACs) in the treatment guidelines for atrial fibrillation has improved the quality of life, as NOACs do not require close monitoring or dose adjustments. However, even if the safety profile of the NOACs regarding the hemorrhagic risk is superior to vitamin K antagonists, the problem raised by an unexpected hemorrhage (e.g. severe hemorrhage after an accident) and the need for efficient hemostasis in a chronic anticoagulated patient has remained unsolved. To find a solution for this problem, reversal agents for NOACs have been developed and tested, and two of them, idarucizumab and andexanet-alpha, have already been approved by the FDA, thus making NOACs increasingly appealing as a choice of anticoagulation treatment

Optimisation of anticoagulation in patients with atrial fibrillation

Atrial fibrillation is a common cardiac arrhythmia associated with debilitating complications, one of which is stroke. Anticoagulants (warfarin and the non-vitamin K antagonist oral anticoagulants) are recommended for stroke prophylaxis, their utilisation however requires stroke risk reduction to be balanced against hemorrhage risk. Current review of the literature suggests that despite the presence of risk stratification tools such as the CHADS2 and the newer CHA2DS2-VASc, clinicians often find it challenging to anticipate the risk-benefit ratio of anticoagulation. This results in both the underuse and overuse of anticoagulation in patients as well as uncertainty over whether to use anticoagulation in paroxysmal AF. This review looks at optimising anticoagulation by improving the assessment of bleeding risk and by improving the assessment of stroke risk. The percutaneous occlusion of the left atrial appendage is an emerging alternative to oral anticoagulation therapy.peer-reviewe

Outcomes Associated With Oral Anticoagulants Plus Antiplatelets in Patients With Newly Diagnosed Atrial Fibrillation.

Importance: Patients with nonvalvular atrial fibrillation at risk of stroke should receive oral anticoagulants (OAC). However, approximately 1 in 8 patients in the Global Anticoagulant Registry in the Field (GARFIELD-AF) registry are treated with antiplatelet (AP) drugs in addition to OAC, with or without documented vascular disease or other indications for AP therapy. Objective: To investigate baseline characteristics and outcomes of patients who were prescribed OAC plus AP therapy vs OAC alone. Design, Setting, and Participants: Prospective cohort study of the GARFIELD-AF registry, an international, multicenter, observational study of adults aged 18 years and older with recently diagnosed nonvalvular atrial fibrillation and at least 1 risk factor for stroke enrolled between March 2010 and August 2016. Data were extracted for analysis in October 2017 and analyzed from April 2018 to June 2019. Exposure: Participants received either OAC plus AP or OAC alone. Main Outcomes and Measures: Clinical outcomes were measured over 3 and 12 months. Outcomes were adjusted for 40 covariates, including baseline conditions and medications. Results: A total of 24 436 patients (13 438 [55.0%] male; median [interquartile range] age, 71 [64-78] years) were analyzed. Among eligible patients, those receiving OAC plus AP therapy had a greater prevalence of cardiovascular indications for AP, including acute coronary syndromes (22.0% vs 4.3%), coronary artery disease (39.1% vs 9.8%), and carotid occlusive disease (4.8% vs 2.0%). Over 1 year, patients treated with OAC plus AP had significantly higher incidence rates of stroke (adjusted hazard ratio [aHR], 1.49; 95% CI, 1.01-2.20) and any bleeding event (aHR, 1.41; 95% CI, 1.17-1.70) than those treated with OAC alone. These patients did not show evidence of reduced all-cause mortality (aHR, 1.22; 95% CI, 0.98-1.51). Risk of acute coronary syndrome was not reduced in patients taking OAC plus AP compared with OAC alone (aHR, 1.16; 95% CI, 0.70-1.94). Patients treated with OAC plus AP also had higher rates of all clinical outcomes than those treated with OAC alone over the short term (3 months). Conclusions and Relevance: This study challenges the practice of coprescribing OAC plus AP unless there is a clear indication for adding AP to OAC therapy in newly diagnosed atrial fibrillation

Appropriateness of oral anticoagulants for long-term treatment of atrial fibrillation in older people: results of an evidence-based review and international consensus validation process (OAC-FORTA 2016)

Background: Age appropriateness of anticoagulants for stroke prevention in atrial fibrillation is uncertain. Objective: To review oral anticoagulants for the treatment of atrial fibrillation in older (age >65 years) people and to classify appropriate and inappropriate drugs based on efficacy, safety and tolerability using the Fit-fOR-The-Aged (FORTA) classification. Methods: We performed a structured comprehensive review of controlled clinical trials and summaries of individual product characteristics to assess study and total patient numbers, quality of major outcome data and data of geriatric relevance. The resulting evidence was discussed in a round table with an interdisciplinary panel of ten European experts. Decisions on age appropriateness were made using a Delphi process. Results: For the eight drugs included, 380 citations were identified. The primary outcome results were reported in 32 clinical trials with explicit and relevant data on older people. Though over 24,000 patients aged >75/80 years were studied for warfarin, data on geriatric syndromes were rare (two studies reporting on frailty/falls/mental status) and missing for all other compounds. Apixaban was rated FORTA-A (highly beneficial). Other non-vitamin K antagonist oral anticoagulants (including low/high-intensity dabigatran and high-intensity edoxaban) and warfarin were assigned to FORTA-B (beneficial). Phenprocoumon, acenocoumarol and fluindione were rated FORTA-C (questionable), mainly reflecting the absence of data. Conclusions: All non-vitamin K antagonist oral anticoagulants and warfarin were classified as beneficial or very beneficial in older persons (FORTA-A or -B), underlining the overall positive assessment of the risk/benefit ratio for these drugs. For other vitamin-K antagonists regionally used in Europe, the lack of evidence should challenge current practice

Anticoagulants for acute ischaemic stroke

Peer reviewedPublisher PD

Changing the approach to anticoagulant therapy in older patients with multimorbidity using a precision medicine approach

The ageing of the world population has resulted in an increase in the number of older patients with multimorbid conditions receiving multiple therapies. This emerging clinical scenario poses new challenges, which are mostly related to the increased incidence of adverse effects. This translates into poor clinical care, reduced cost-effectiveness of drug therapies, and social isolation of multimorbid patients due to reduced autonomy. A strategy to address these emerging challenges could involve the personalization of therapies based on the clinical, molecular, and genetic characterization of multimorbid patients. Anticoagulation therapy is a feasible model to implement personalized medicine since it generally involves older multimorbid patients receiving multiple drugs. In this study, in patients with atrial fibrillation, the use of the new generation of anticoagulation therapy, i.e., direct oral anti-coagulants (DOACs), is based on a preliminary assessment of the molecular targets of DOACS and any possible drug–drug interactions. Then, the genetic polymorphism of enzymes metabolizing DOACs is studied. After DOAC prescription, its circulating levels are measured. Clinical data are being collected to assess whether this personalized approach improves the safety and efficacy profiles of anticoagulation therapy using DOACs, thereby reducing the costs of healthcare for ageing multimorbid patients

Association between patient outcomes and key performance indicators of stroke care quality: A systematic review and meta-analysis

Purpose: Translating research evidence into clinical practice often uses key performance indicators to monitor quality of care. We conducted a systematic review to identify the stroke key performance indicators used in large registries, and to estimate their association with patient outcomes. Method: We sought publications of recent (January 2000–May 2017) national or regional stroke registers reporting the association of key performance indicators with patient outcome (adjusting for age and stroke severity). We searched Ovid Medline, EMBASE and PubMed and screened references from bibliographies. We used an inverse variance random effects meta-analysis to estimate associations (odds ratio; 95% confidence interval) with death or poor outcome (death or disability) at the end of follow-up. Findings: We identified 30 eligible studies (324,409 patients). The commonest key performance indicators were swallowing/nutritional assessment, stroke unit admission, antiplatelet use for ischaemic stroke, brain imaging and anticoagulant use for ischaemic stroke with atrial fibrillation, lipid management, deep vein thrombosis prophylaxis and early physiotherapy/mobilisation. Lower case fatality was associated with stroke unit admission (odds ratio 0.79; 0.72–0.87), swallow/nutritional assessment (odds ratio 0.78; 0.66–0.92) and antiplatelet use for ischaemic stroke (odds ratio 0.61; 0.50–0.74) or anticoagulant use for ischaemic stroke with atrial fibrillation (odds ratio 0.51; 0.43–0.64), lipid management (odds ratio 0.52; 0.38–0.71) and early physiotherapy or mobilisation (odds ratio 0.78; 0.67–0.91). Reduced poor outcome was associated with adherence to swallowing/nutritional assessment (odds ratio 0.58; 0.43–0.78) and stroke unit admission (odds ratio 0.83; 0.77–0.89). Adherence with several key performance indicators appeared to have an additive benefit. Discussion: Adherence with common key performance indicators was consistently associated with a lower risk of death or disability after stroke. Conclusion: Policy makers and health care professionals should implement and monitor those key performance indicators supported by good evidence

Efficacy of three anticoagulant rodenticides for the control of poison-shy Rattus rattus

House rats (Rattus rattus) which do not consume a lethal dose of zinc phosphide develop poison-shyness after a single exposure. The surviving poison-shy rats cannot be baited again with zinc phosphide for about three months. Poison-shy rats were separately given anticoagulant baits (brodifacoum 0.005%, coumatetralyl and warfarin 0.025%) in no-choice tests. The first two anticoagulants were found to be the most efficient ones. It was observed that those R. rattus which had consumed 56.7 mg/kg or more zinc phosphide died sooner (P < 0.05 to 0.1) after anticoagulant poisoning when compared with normal rats. It is conjectured that prothrombin inhibition is accelerated in the liver of poison-shy R. rattus due to the action of phosphine present in the earlier ingested sublethal dose of zinc phosphide