New oral anticoagulants: An emergency department overview

As of September 2013, three new oral anticoagulants (NOACs) are now available for clinical use on the Pharmaceutical Benefits Scheme in Australia. All three are for stroke prevention in atrial fibrillation, and one will also be available for the treatment of deep venous thrombosis and pulmonary embolism. All have been evaluated in large, multicentre randomised clinical trials. These drugs show at least equivalent efficacy to the current standard of care, the vitamin K antagonist warfarin. Major bleeding rates are overall comparable with warfarin, but there is an important reduction in intracranial bleeding of approximately 50% with all NOAC agents. The NOACs are administered in a simple, fixed dose regimen. There are a few clinically important interactions with other medications or diet. Concerns exist about the potential for irreversible bleeding in the small number of patients in which that occurs. This short report will discuss the pharmacology of these agents, the indications for use, aspects of laboratory monitoring and the management of bleeding with these agents.     

The use of oral anticoagulants for the treatment of venous thromboembolic events in an ED

Venous thromboembolism (VTE) is a disease spectrum that ranges from deep vein thrombosis (DVT) to pulmonary embolism (PE). Rapid diagnosis and treatment of VTE by emergency care providers are critical for decreasing patient mortality, morbidity, and the incidence of recurrent events. Recent American College of Chest Physicians guidelines recommend initial treatment with unfractionated heparin, low–molecular weight heparin, or fondaparinux overlapped with warfarin for a minimum of 5 days for the treatment of VTE in most cases. Warfarin monotherapy is thereafter continued for 3, 6, or 12 months. These guidelines were published before the approval of target-specific oral anticoagulants (TSOACs), and they have yet to be updated to reflect these new treatment options. For some patients, TSOACs, which act by directly inhibiting factor IIa or factor Xa, may provide safer, more convenient alternatives to warfarin. Their advantages include ease of use, reduced monitoring requirements, and lower bleeding risk than traditional therapy. Additionally, clinical trials have established noninferiority of TSOACs to warfarin for the prevention of recurrent VTE. These trials have demonstrated that TSOACs exhibit similar or lower bleeding rates, particularly intracranial bleeding rates compared with warfarin. Anticoagulation therapy with TSOACs may allow early discharge or outpatient management options for low-risk patients with DVT and PE. This review addresses the importance of early diagnosis and treatment of VTE, outcomes of VTE risk assessment, key efficacy and safety data from phase 3 clinical trials for the various TSOACs for the treatment of DVT and PE, and the corresponding considerations for clinical practice.     

新型口服抗凝药物——抗凝治疗新选择

无论治疗急性血栓栓塞事件还是降低血栓栓塞风险,抗凝药物临床应用均需权衡抗凝治疗获益和潜在出血风险.长期以来,首选和标准长期口服抗凝治疗药物是维生素K拮抗剂(VKA),如华法林.VKA主要通过影响维生素K依赖的凝血因子Ⅱ、Ⅶ、Ⅸ、Ⅹ合成发挥抗凝作用,同时因影响蛋白C、蛋白S、蛋白Z合成,故在抗凝初期存在潜在的促凝作用.新型口服抗凝药物发展趋势是作用于单一靶点、直接发挥抗凝作用、方便长期口服.     

Clinical review: Clinical management of new oral anticoagulants: a structured review with emphasis on the reversal of bleeding complications

New oral anticoagulants, including dabigatran, rivaroxaban, and apixaban, have been recently approved for primary and secondary prophylaxis of thromboembolic conditions. However, there is no clear strategy for managing and reversing their anticoagulant effects. We aimed to summarize the available evidence for clinical management and reversal of bleeding associated with new oral anticoagulants. Using a systematic review approach, we aimed to identify studies describing reversal strategies for dabigatran, rivaroxaban, and apixaban. The search was conducted using Medline, EMBASE, HealthSTAR, and grey literature. We included laboratory and human studies. We included 23 studies reported in 37 out of 106 potentially relevant references. Four studies were conducted in humans and the rest were in vitro and in vivo studies. The majority of the studies evaluated the use of prothrombinase complex concentrate (PCC), either activated or inactivated, and recombinant activated factor VII (rFVIIa). Other interventions were also identified. Laboratory studies suggest that hemostatic parameters and bleeding might be partially or completely corrected by PCC for rivaroxaban better than dabigatran. Studies in humans suggest that PCC might reverse the effects of rivaroxaban better than dabigatran assessed by hemostatic tests. We were not able to locate studies evaluating the clinical efficacy of these agents. The best available evidence suggests that PCC (activated or inactivated) might be the best option for reversing new anticoagulants. Evidence for rFVIIa is less compelling. There might be differences in the efficacy of reversing agents for different anticoagulants. Studies assessing the clinical efficacy of these reversal agents are urgently needed.     

Patient ED turnaround times: a comparative review

Patient turnaround times in emergency departments (EDs) are receiving increasing attention by patients, medical staff, hospital administrators, payers, and regulatory agencies. A retrospective study of ED turnaround times by hospitals identified by Modern Healthcare as being in the top 100 hospitals in the United States was undertaken. Five different categories of hospitals were studied. The shortest turnaround times occurred in rural hospitals with less than 250 beds and the longest times were in major academic centers with more than 400 beds.     

Medication taking behaviors in patients taking warfarin versus direct oral anticoagulants: A systematic review

Introduction: This article aims to compare medication adherence and persistence between warfarin and direct oral anticoagulants (DOACs) and identify reported adherence barriers. As with other chronic illness, medication nonadherence continues to be a problem and appropriate adherence to long-term anticoagulation therapy is needed to improve patient health outcomes and to reduce health expenditure associated with hospitalizations and emergency visits.

Areas covered: Warfarin and DOACs such as apixaban, rivaroxaban, edoxaban, and dabigatran have demonstrated effectiveness in the management of atrial fibrillation (AF), deep vein thrombosis (DVT), and pulmonary embolism (PE). Adherence and long-term persistence to oral anticoagulants is highly associated with reduced adverse events. A systematic literature search from 2013 to 2018 examined the primary outcome of adherence and persistence.

Expert opinion: Currently, warfarin is less preferred over DOACs due to associated complications like narrow therapeutic window, inconvenience, and increased risk of adverse events. At the same time, the lack of monitoring with DOACs in combination with cost issues may negatively impact medication adherence. Examining adherence barriers identified in the literature is the first step to designing effective interventions aimed at enhancing adherence in this high-risk population.     

Hepatitis B screening in an argentine ED: Increasing vaccination in a resource-limited setting

BackgroundThere is limited data regarding the use of emergency departments (EDs) for infectious disease screening and vaccination in resource-limited regions. In these settings, EDs are often the only contact that patients have with the healthcare system, turning an ED visit into an opportune time to deliver preventative health services.MethodsIn this pilot study, patients that met inclusion criteria were prospectively tested for hepatitis B surface antigen test (HBsAg). Previously unvaccinated patients who tested negative for HBsAg were offered HBV vaccination. The study setting was a public infectious disease hospital in Cordoba, Argentina. The primary outcomes were new HBV diagnoses, as well as vaccination completion between screening modalities (Point-of-Care-Testing-POCT vs. laboratory testing) and same vs. different day vaccination.ResultsWe screened 100 patients for HBV (75 POCT & 25 laboratory). The median age of participants was 35 years (IQR 24-52) and 55% were male. No patients tested positive for HBsAg. All patients who completed first dose vaccination were initially screened with the POCT. No patients screened with laboratory testing returned for vaccination. Patients who were scheduled for vaccination the same day were more likely to complete vaccination compared to those scheduled for another day (75% vs. 14%, p < .001).ConclusionOur study supports the use of HBV POCTs in the ED in conjunction with vaccination of HBV-negative individuals. In regions with low HBV endemicity, direct vaccination without HBsAg testing may be more cost effective. We believe that this acute-care screening model is applicable to other resource-limited settings.     

Impact of bariatric surgery on oral anticoagulants pharmacology,and consequences for clinical practice: a narrative review

The prevalence of obesity has been steadily increasing in recent years worldwide. At the same time bariatric surgery, the best therapeutic strategy to date in terms of sustainable weight loss and improvement of associated comorbidities has been also increasing. However, these surgeries, whether primarily restrictive or malabsorptive, raise questions about the pharmacology of oral drugs. Among widely used drugs, anticoagulants are the referent therapy to treat some cardiovascular diseases such as atrial fibrillation and venous thromboembolism. How bariatric surgery may impact pharmacological properties of oral anticoagulants, and more specifically, direct oral anticoagulants (DOACs) are difficult to anticipate. In this review, we describe available data concerning the potential impact of bariatric surgery on the pharmacology of oral anticoagulants. The vitamin K antagonists (VKAs) requirements for the same international normalized ratio target are reduced after bariatric surgery. Limited data available for dabigatran 150 mg twice daily indicate a risk of insufficient efficacy in atrial fibrillation after gastric bypass due to probable impaired absorption. Data for rivaroxaban at the prophylactic dose of 10 mg per day suggest no impact of bariatric surgery from 3 days to 8 months post‐surgery. However, no conclusive data are available for other anticoagulants or the use of DOACs at therapeutic doses. To date, DOACs are not recommended in patients who have undergone bariatric surgery, because of limited available data. Pending new studies to confirm the predictable pharmacokinetics and safety of DOACs in this population, especially at therapeutic doses, VKAs remain the first option for chronic anticoagulation.     

New anticoagulants: an update

There has been an explosion of new anticoagulants in recent years. new parenteral anticoagulants have been developed to overcome the limitations of heparin and low molecular weight heparin , whereas novel orally active anticoagulants have been designed to provide more streamlined therapy than vitamin K antagonists. Focusing on drugs in more advanced stages of clinical testing, this review identifies the molecular targets of new anticoagulants, describes the results of clinical trials, and provides perspective on the opportunities for new anticoagulants.     

New oral anticoagulants to revolutionise venous thromboembolism (VTE) management

Warfarin, a vitamin K antagonist has been the mainstay of venous thromboembolism treatment for over 60 years. However, it has significant limitations in relation to achieving a safe and therapeutic efficacy. Evolution in the development of oral anticoagulants to offset the drawbacks of warfarin, has led to the introduction of two new oral anticoagulants, namely dabigatran, a direct thrombin inhibitor and rivaroxaban, a direct factor Xa inhibitor. This paper examines the potential of the two new oral anticoagulants to offer a safer therapeutic alternative to warfarin, as well as their clinical efficacy in relation to the prevention of venous thromboembolism in patients undergoing hip and knee replacement surgery. In seven randomized clinical trials, dabigatran has demonstrated noninferior efficacy to enoxaparin, with a similar safety profile. Following a single technology appraisal of dabigatran, The National Institute of Clinical Excellence (NICE) have now endorsed its clinical efficacy as a serious alternative to low molecular weight heparin and fondaparinux.Three randomized clinical trials have also concluded that rivaroxaban is as efficacious and safe as enoxaparin in the prevention of venous thromboembolism for patients undergoing major orthopaedic surgery of the lower limbs. In a single technology appraisal, rivaroxaban within its marketing authorisation was recommended by NICE in April 2009, as an option for the prevention of venous thromboembolism in adults having elective hip or knee replacement surgery.     

Medication prescribing errors in the prehospital setting and in the ED

Background

Medication errors are a common cause of iatrogenic adverse drug events. The incidence and nature of medication errors during prehospital treatment have not been fully described.

Objectives

The objectives of this study are to describe the incidence and characteristics of medication errors in adults during prehospital emergency treatment and in the emergency department (ED) and to identify risk factors for medication errors in those settings.

Methods

This is a retrospective study of adult patients transferred by emergency medical services to the ED of a university-affiliated hospital in Israel. The drugs administered in the mobile intensive care unit and in the ED were reviewed by 2 reviewers, who independently decided whether an error had occurred. The primary outcome was the number of drug errors per patient. Secondary outcomes were the type and severity of the errors and variables associated with increased incidence of drug errors.

Results

During the study period, 1837 patients were brought to the ED by mobile intensive care unit vehicles. Five hundred thirty-six patient charts (29%) were randomly selected for review; 65 charts (12.12%) could not be found; thus, 471 charts were reviewed. In the emergency vehicle, 188 patients (45.63%) received medications; of those, 12.76% (24 patients) were subject to a medication error. The number of drugs administered and long evacuation times were associated with higher risk for an error (P < .01 and P = .011, respectively). The presence of a physician in the emergency vehicle did not alter the risk of an error (P = .95). In the ED, 332 patients (72.6%) received medications. Of those, medication errors occurred in 120 patients (36.1%). The more medications administered, the higher the risk of error (P < .01). Less errors occurred in trauma patients (P = .041).

Conclusion

More medication errors occur in the ED than in the emergency vehicles. Patients treated with multiple medications are more prone to medication errors.     

HIV rapid testing in a Veterans Affairs hospital ED setting: a 5-year sustainability evaluation

Routine HIV testing in primary care settings is now recommended in the United States. The US Department of Veterans Affairs (VA) has increased the number of patients tested for HIV, but overall HIV testing rates in VA remain low. A proven strategy for increasing such testing involves nurse-initiated HIV rapid testing (HIV RT). The purpose of this work was to use a mixed methodology approach to evaluate the 5-year sustainability of an intervention that implemented HIV RT in a VA emergency department setting in a large, urban VA medical center to reduce missed diagnostic and treatment opportunities in this vulnerable patient population. In-person semistructured interviews were conducted with providers and stakeholders. Interview notes were qualitatively coded for emerging themes. Quarterly testing rates were evaluated for a 5-year time span starting from the launch in July 2008. Findings indicate that HIV RT was sustained by the enthusiasm of 2 clinical champions who oversaw the registered nurses responsible for conducting the testing. The departure of the clinical champions was correlated with a substantial drop-off in testing. Findings also indicate potential strategies for improving sustainability including engaging senior leadership in the project, engaging line staff in the implementation planning from the start to increase ownership over the innovation, incorporating information into initial training explaining the importance of the innovation to quality patient care, providing ongoing training to maintain skills, and providing routine progress reports to staff to demonstrate the ongoing impact of their efforts.