达比加群酯对急性心肌梗死并发心房颤动患者凝血功能和预后的影响

目的 探讨达比加群酯对急性心肌梗死（AMI）并发心房颤动患者凝血功能和预后的影响。方法 280例AMI并发心房颤动患者随机分为两组。除给予相同基础治疗外,对照组给予华法林,观察组给予达比加群酯。比较两组治疗前后的凝血功能指标和预后。结果 治疗后,观察组的PT、 INR、 TT、 APTT均高于对照组,FIB低于对照组（P <0.05）。两组的少量出血和大量出血发生率比较,差异无统计学意义（P>0.05）;但观察组的血栓栓塞形成率、轻微出血发生率和心肌梗死再发生率均低于对照组（P <0.05）。结论 达比加群酯治疗AMI并发心房颤动可提高抗凝有效性,降低血栓栓塞、出血和心肌再梗死发生率。     

三种不同抗凝方式用于心房颤动导管消融术患者中的临床效果及经济成本对比分析

目的探讨达比加群、利伐沙班及华法林用于心房颤动导管消融术患者中的临床效果及经济成本。方法以2015年2月-2017年2月在我院行房颤射频消融术的120例患者为研究对象,根据治疗方式分为达比加群组、利伐沙班组和华法林组,分析比较三组的治疗效果和治疗成本。结果治疗后,达比加群组和利伐沙班组活化的部分凝血活酶时间(APTT)、凝血酶时间(TT)明显长于华法林组(P0.05)。达比加群组和利伐沙班组并发症发生率明显低于华法林组(P0.05)。3组患者不良反应发生情况比较无显著差异(P0.05)。达比加群组、利伐沙班组及华法林组患者每人每年药物费用分别为12 168元、24 120元及108元,华法林组患者总费用明显低于达比加群组和利伐沙班组患者。结论达比加群和利伐沙班用于心房颤动导管消融术后抗凝治疗中,临床效果与华法林相当,但费用较高,根据我国平均经济水平来看,华法林经济有效。     

抗凝药物怎样吃才安全有效?

<正>抗凝药物主要用于血栓栓塞性疾病的预防和治疗,包括心脏瓣膜置换术后的长期或终身抗凝、心房颤动患者缺血性脑卒中的预防、深静脉血栓和肺栓塞的治疗、髋关节或膝关节置换术后静脉血栓的预防,以及一些血栓高危患者静脉血栓的预防等。目前,临床上将常用的口服抗凝药物分为两种类型：一种是维生素K拮抗剂,以华法林为代表;另一种是非维生素K拮抗剂,又称为新型口服抗凝药,包括达比加群酯、利伐沙班、艾多沙班、阿哌沙班等。     

口服抗凝药在心房颤动患者预防脑卒中的效益风险评估

目的评价口服抗凝药的效益风险情况,为房颤患者抗凝治疗的选择提供依据。方法根据三项大型Ⅲ期临床试验数据,构建口服抗凝药的效益风险树状图,在精确权重信息未知与已知两种情况下,分别构建SMAA模型,观察新型口服抗凝药效益风险情况。结果相比华法林治疗,新型口服抗凝药治疗降低了多数临床事件的发生;效益风险评估结果显示,在两种不同权重信息的情况下,达比加群酯150mg BID均显示成为最佳药物的概率最大,可接受度分别为0.43与0.48,置信度分别为0.44与0.49;其次为阿哌沙班与利伐沙班。结论在两种不同权重信息情况下,达比加群酯150mg BID的效益风险最好,其次为阿哌沙班、利伐沙班,华法林效益风险最低。     

老年房颤患者华法林抗凝治疗的护理体会

根据我国流行病学研究,房颤的总患病率为0．77％,且随年龄增长而增长,80岁以上人群心房颤动的发生率7．5％[1]。房颤是最常见的心律失常,其最严重的并发症之一是体循环血栓栓塞,特别是脑卒中,严重影响老年患者的生活质量。华法林抗凝治疗可以显著降低房颤患者的血栓栓塞率,但我国目前仅有2％的房颤患者应用华法林治疗,原因主要是应用华法林所致出血并发症而且老年患者常有肝、肾功能不全,或有痴呆,影响用药依从性。本文着重探讨房颤患者用华法林治疗过程中的护理要点,现将护理体会总结如下。     

新型口服抗凝药物在非瓣膜性房颤卒中预防中的应用进展

<正>心房颤动(房颤)是临床上最常见的心律失常之一。在美国,房颤在一般人群中患病率超过1%,80岁以上人群超过10%,非瓣膜性房颤可使缺血性卒中发生风险增加4~5倍[1]。我国房颤的患病率约为0.61%,在70岁的非瓣膜性房颤患者中,缺血性脑卒中的发生率为5.3%,房颤住院患者的脑卒中患病率达24.8%,80岁以上患者患病率高达32.9%[2]。过去60年来,维生素K拮抗剂(以华法林为代表)是唯一可用的口服抗凝药     

达比加群酯联合阿司匹林治疗非瓣膜性房颤效果分析

目的探究达比加群酯联合阿司匹林在非瓣膜性房颤病症方面的临床疗效。方法择取我院接受治疗的146例非瓣膜性房颤患者,依照用药方案的不同将其均分至对照、观察两组。给予对照组患者常规胺碘酮及其华法林药物进行治疗,而观察组患者则令其服用达比加群酯+阿司匹林联合用药进行治疗,对比分析两组非瓣膜性房颤患者的临床疗效差异。结果对照、观察两组临床总有效率分别为78.45%和94.52%,差异显著,同时,两组治疗前后各抗凝指标均有显著改善,而组间相比观察组患者抗凝指标提高更为显著,P﹤0.05有统计学意义。采观察组患者不良反应率为30.13%,明显优于对照组的60.27%,P﹤0.05,统计学意义明显。结论达比加群酯联合阿司匹林治疗非瓣膜性房颤不仅能够有效提高各抗凝指标,而且能够显著降低不良反应的发生。     

华法林抗凝治疗的安全性与护理 ——一例华法林治疗中毒病例引发的关于华法林在治疗与监测护理方面的反思

华法林是深静脉血栓、心房颤动血栓栓塞、瓣膜病等血栓栓塞性疾病常用的口服抗凝药.但华法林治疗窗窄、剂量变异性大、影响药效因素多,因此华法林抗凝治疗的安全有效离不开良好的监测管理与护理.本文通过对一例华法林中毒病例和华法林药理特性的分析,结合自身的临床经验,可以从患者教育、INR监测、药物相互作用、组建抗凝门诊、患者自我管理以及对患者生活饮食指导等方面的护理提高华法林抗凝治疗的安全性.     

华法林预防瓣膜病伴心房颤动患者血栓栓塞的临床观察

目的观察华法林对瓣膜病伴心房颤动（房颤）患者血栓栓塞发生的预防和安全性。方法将确诊为二尖瓣狭窄伴房颤患者197例分为华法林抗凝和阿司匹林抗血小板治疗两组，观察两组血栓栓塞并发症及出血等不良反应的发生率。结果华法林组血栓栓塞年发生率为0．55％，阿斯匹林组为3．85％，两组比较差异有显著性（P〈0．05），其不良反应为出血倾向及皮疹、消化道反应。结论华法林抗凝强度国际标准化比值（INR）2．0—3．0，较单纯阿斯匹林抗血小板治疗降低瓣膜病伴房颤患者血栓栓塞的发生率有明显优越性，且安全性好。     

1例脑梗塞老年患者应用华法林的药学监护

华法林是双香豆素衍生物,临床实践中常用抗凝血剂,用于防治各种血栓栓塞性疾病。1例脑梗塞合并多种基础疾病患者,有房颤史,入院后给予改善脑组织血液循环及能量代谢、抗凝、营养神经细胞、降脂稳斑、控制血压、护胃等药物治疗,但INR值一直未达标,华法林剂量已达5. 625 mg。对患者进行VKORC1和CYP2C9基因检测,运用多元线性回归分析法(MRA)和最大后验贝叶斯法(MAPB)预测华法林的日剂量分别是2. 43 mg和9. 8 mg。考虑患者在抗凝治疗期间已出现两次尿隐血,临床药师建议停用华法林改用达比加群酯。该案例根据基因检测结果运用不同模型综合考虑各种因素,为华法林患者制定了个体化给药方案,提供理想抗凝效果,减少出血和栓塞等不良反应。     

Efficacy and Safety of Oral Anticoagulants in Older Adult Patients With Atrial Fibrillation: Pairwise and Network Meta-Analyses

ObjectiveTo evaluate the efficacy and safety of oral anticoagulants for older adult patients with atrial fibrillation (AF).DesignPairwise and network meta-analyses.Setting and ParticipantsPatients with AF aged ≥75 years.MethodsPubMed, Embase, and the Cochrane library were searched for published randomized controlled trials and adjusted observational studies evaluating the use of a non–vitamin K antagonist oral anticoagulants (NOACs), vitamin K antagonist, or antiplatelet drug for the prevention of stroke. The primary efficacy and safety outcomes were the composite of stroke and systemic embolism (SSE) and major bleedings.ResultsThis study included 38 studies enrolling 1,022,908 older adult patients with AF. Results from pairwise meta-analyses showed that NOACs were superior to warfarin for all outcomes, except that dabigatran increased the risk of gastrointestinal (GI) bleedings. Aspirin was associated with a higher risk of SSE and ischemic stroke than warfarin or NOACs. Results of network meta-analyses indicated that apixaban significantly reduced the risk of SSE, major bleedings, and GI bleedings than warfarin, rivaroxaban, and dabigatran. Apixaban, edoxaban, rivaroxaban, and dabigatran reduced the risk of ischemic stroke and intracranial bleeding compared to warfarin. Dabigatran showed lower risk of all-cause mortality than warfarin and of intracranial bleeding than rivaroxaban.Conclusions and ImplicationsNOACs are of at least equal efficacy, or even superior to warfarin. The safety profile of individual NOAC agents was significantly different, as apixaban performs better than the other oral anticoagulants in reducing major bleeding and GI bleeding, whereas dabigatran increased the risk of GI bleeding.     

The Cheno Cooperative Study: Its Meaning for Gallstone Treatment

Abstract

Novel oral anticoagulants (OACs), including dabigatran etexilate, rivaroxaban, and apixaban, are available alternative anticoagulant therapy to vitamin K antagonists. The US Food and Drug Administration (FDA) has approved dabigatran, rivaroxaban, and apixaban for the treatment of appropriate patients for specific clinical indications. Therapeutic advantages of prescribing the new OACs are related to their predictable pharmacokinetic and pharmacodynamic properties. Dabigatran, rivaroxaban, and apixaban have all been shown to be noninferior to warfarin treatment for stroke prevention in respective phase 3 clinical trials; dabigatran and apixaban were shown to be superior to warfarin as preventive therapy. Dabigatran, rivaroxaban, and apixaban are all approved agents for stroke prevention in patients with nonvalvular atrial fibrillation in the United States and Europe. Among these agents, rivaroxaban is the only FDA-approved drug for the treatment of venous thromboembolism. This article reviews the major clinical trials that investigated the efficacy and safety of the new OACs and the use of these agents in special clinical situations.     

Target-specific oral anticoagulants and the hospitalist

As a class, the target-specific oral anticoagulants (TSOACs) are at least as effective as warfarin, often with superior safety for the prevention of stroke in patients with nonvalvular atrial fibrillation (AF) and the treatment of acute venous thromboembolism (VTE) and prevention of recurrent VTE. Currently, dabigatran, the direct thrombin inhibitor, along with rivaroxaban and apixaban, direct factor Xa inhibitors, has been approved in multiple countries for these indications. Edoxaban, which has received approval for the abovementioned indications in Japan, has demonstrated efficacy and safety comparable to or better than warfarin in Phase III clinical trials and is under further regulatory consideration. It is anticipated that the use of TSOACs will increase as practitioners and healthcare systems gain familiarity with these drugs and adopt their use into clinical practice. This review will provide a brief overview of the TSOAC Phase III clinical trials for prevention of stroke and systemic embolic events in patients with AF and the Phase III clinical trials for the prevention of recurrent VTE, discuss current treatment guidelines, address how TSOACs may help meet national safety goals, and provide clinical decision-making guidance regarding the use of TSOACs for hospitalists.     

Evaluation of Dabigatran for Appropriateness of Use and Bleeding Events in a Community Hospital Setting

Background

Warfarin has been the predominant anticoagulant for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF). Its disadvantages are well-known and include a narrow therapeutic index, drug interactions, and the need for frequent monitoring. Dabigatran etexilate, a direct thrombin inhibitor, presents less complexity in prescribing and has emerged as an alternate therapy to warfarin. Although dabigatran does not require routine monitoring, concerns associated with its use include the lack of a reversal agent, complex dose adjustments, and limited guidance to the management of drug interactions.

Objectives

The goals of this study are to describe and to evaluate the use of dabigatran at a community hospital to identify areas for improvement in its prescribing.

Methods

This retrospective chart review of patients at a community hospital in St Louis, MO, included patients who received at least 1 dose of dabigatran between December 2010 and June 2012. The appropriateness of dabigatran was evaluated based on recommendations approved by the US Food and Drug Administration for stroke prophylaxis in the setting of NVAF. The composite end point of bleeding included hospital readmission within 1 year of receiving at least 1 dose of dabigatran at the study institution secondary to bleeding, bleeding associated with a decrease in hemoglobin level by ≥2 g/dL or transfusion of ≥2 units of blood, or a notation of bleeding in the patient''s medical record.

Results

Of the 458 patients included in the evaluation, 76 (16.6%) patients receiving dabigatran were using an inappropriate regimen of this drug, based on dose and frequency on the first day of therapy of dabigatran or the presence of valvular disease. Many patients (42.3%) received at least 1 dose of a concomitant parenteral anticoagulant. The composite end point for bleeding was reported in 66 (14.4%) patients, including 23 (5%) with confirmed gastrointestinal bleeding.

Conclusions

High-risk medications such as dabigatran require monitoring of prescribing habits to improve patient safety and outcomes. Various initiatives, such as pharmacist interventions, therapeutic interchanges, and obtaining appropriate patient parameters, can be implemented in the practice setting to ensure the appropriate use of oral anticoagulants and improved patient outcomes.Oral anticoagulation has changed drastically in the past 4 years with the US Food and Drug Administration (FDA) approval of 3 new agents—dabigatran, rivaroxaban, and apixaban. Warfar-in has had a primary role in oral anticoagulation therapy for many decades. Although its efficacy and safety have been established, therapy with warfarin is associated with significant challenges, including the need for frequent monitoring, drug interactions, a delayed time to onset, and a narrow therapeutic index.1,2 The challenges associated with warfarin not only affect its efficacy, but they also impact patient satisfaction. These concerns have contributed to the development of novel oral anticoagulants, beginning with dabigatran etexilate.Dabigatran etexilate, a direct thrombin inhibitor, was approved by the FDA in October 2010 and is the first novel oral anticoagulant approved to reduce the risk for stroke in patients with nonvalvular atrial fibrillation (NVAF).3 Results from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) study demonstrated the superiority of dabigatran 150 mg orally twice daily compared with warfarin for the prevention of stroke and systemic embolism in patients with NVAF.4 In that study, the rate of major bleeding was similar between the agents; however, dabigatran demonstrated a lower risk for intracranial hemorrhage, but with an increased risk for major gastrointestinal (GI) bleeding, compared with warfarin.4A recent analysis performed by the FDA confirmed these findings.5,6 In this analysis, compared with warfarin, dabigatran demonstrated lower rates of ischemic stroke, intracranial hemorrhage, and death; however, dabigatran was associated with a significant increase in major GI bleeding.5,6 In April 2014, dabigatran received new FDA indications for the treatment of patients with deep-vein thrombosis (DVT) and pulmonary embolism (PE) and for the risk reduction of recurrent DVT and PE in previously treated patients. Two studies, RE-COVER and RE-COVER II, compared dabigatran 150 mg twice daily with warfarin for the treatment of DVT and PE after 5 to 10 days of parenteral anticoagulation. Both studies demonstrated dabigatran''s noninferiority to warfarin.7,8 When the RE-COVER study was initiated, dabigatran was the only agent approved by the FDA for the risk reduction of recurrent venous thromboembolism (VTE).In November 2011, rivaroxaban, a factor Xa inhibitor, was the second novel oral anticoagulant to receive FDA approval to reduce the risk for stroke in patients with NVAF.9 Results from the ROCKET AF trial demonstrated the noninferiority of rivaroxaban to warfarin for the first occurrence of stroke or systemic embolism.10 In November 2012, rivaroxaban received an additional indication for the treatment of and reduction in the risk for recurrent VTE. Two studies, EINSTEIN-DVT and EINSTEIN-PE, compared rivaroxaban (at an initial dose of 15 mg twice daily for 3 weeks, followed by 20 mg once daily) with enoxaparin 1 mg/kg twice daily for at least 5 days with warfarin and then continued with warfarin after the target international normalized ratio (INR) of 2.0 to 3.0 was reached.11,12 Both studies demonstrated the noninferiority of rivaroxaban to warfarin in time to first recurrent DVT or PE event.11,12In December 2012, the factor Xa inhibitor apixaban was the newest novel oral anticoagulant to receive FDA approval to reduce the risk for stroke in patients with NVAF.13 The ARISTOTLE trial compared apixaban 5 mg twice daily (or 2.5 mg twice daily in select patients) with warfarin.14 Apixaban was superior to warfarin for the primary end point of reducing the risks for stroke and systemic embolism. Superiority to warfarin was primarily attributable to reductions in hemorrhagic stroke and ischemic stroke with hemorrhagic transformation compared with warfarin.14In AVERROES, patients with NVAF who were not candidates for therapy with warfarin were randomized to treatment with apixaban 5 mg twice daily (or 2.5 mg twice daily in select patients) or to aspirin 81 mg to 324 mg once daily.15 The primary objective of the study was to determine if apixaban was superior to aspirin for preventing the outcomes of stroke or systemic embolism. This trial was stopped early on the basis of a prespecified interim analysis that showed significant reductions in stroke and systemic embolism with apixaban compared with aspirin, but apixaban was associated with a modest increase in major bleeding.15

KEY POINTS

• ▸ Anticoagulation has changed drastically in the past 4 years in the United States with the FDA approval of novel oral anticoagulants, starting with dabigatran in 2010, rivaroxaban in 2011, and apixaban in 2012.
• ▸ These new anticoagulants present a safe alternative to warfarin for the prevention of stroke and systemic embolism in the setting of nonvalvular atrial fibrillation (NVAF).
• ▸ However, although anticoagulation has been simplified with the novel oral drugs, many safety issues must be considered when prescribing these agents.
• ▸ This retrospective chart review at a community hospital analyzed the appropriateness use of dabigatran, the first novel anticoagulant to receive FDA approval for the treatment of NVAF.
• ▸ Of the 458 patients included in this study, 76 patients were prescribed an inappropriate, mostly too high, dose of dabigatran.
• ▸ Although dabigatran is only approved for the treatment of NVAF, 13 patients had valvular disease.
• ▸ The majority of the patients were also receiving concomitant medications that are known to have drug interactions with dabigatran.
• ▸ These results indicate that high-risk medications require better monitoring of prescribing habits to improve patient safety and outcomes.

The current guidelines for the treatment of atrial fibrillation provide a class I recommendation for warfarin (level of evidence A) and dabigatran, rivaroxaban, and apixaban (level of evidence B) for the prevention of thromboembolism in patients with a CHA₂DS₂-VAS_c score of ≥2.16Dabigatran provides an effective alternative therapy to warfarin. It offers a predictable pharmacokinetic profile, which eliminates the need for routine monitoring of serum drug concentrations. Approximately 80% of dabigatran is excreted renally and requires dose reductions for patients with reduced creatinine clearance.17 Although dabigatran addresses some of the challenges associated with warfarin, there are remaining issues regarding the use of dabigatran.Warfarin interacts with numerous medications, disease states, and a variety of foods containing vitamin K; however, there is a great deal of clinical experience and resources available to effectively manage many of warfarin''s interactions.1 Unlike warfarin, dabigatran is not metabolized by cytochrome P450 enzymes and has fewer drug interactions. Although several drug interactions with dabigatran and P-glycoprotein inducers and inhibitors have been identified, little guidance has been provided on how to address them in practice.18Additional concerns surrounding dabigatran include the lack of a reversal agent and the lack of availability of laboratory testing to determine its degree of anticoagulation activity. Dabigatran prolongs markers of coagulation, such as the activated partial thromboplastin time (aPTT) and ecarin clotting time, and may potentially impact INR values. The aPTT can only provide an approximation of the anticoagulation effect of dabigatran, and the INR is relatively insensitive to the degree of anticoagulation. The ecarin clotting time is a more specific parameter to determine the effect of anticoagulation19; however, most laboratories are not adequately equipped to perform the laboratory test. Without laboratory parameters to guide dosing adjustments, it is unclear how to balance the drug interactions that have been identified to potentially increase or decrease dabigatran serum concentrations. The lack of monitoring also makes it difficult to manage special populations that typically require dosage adjustments (eg, the elderly, obese patients, underweight patients, and those with renal dysfunction).Since dabigatran became the first oral anticoagulant to be introduced to the US market, and the first to be included on hospital formularies, there has been a dramatic shift in the approach to anticoagulation. Laboratory markers of anticoagulation effect are no longer reliable, drug interactions require significantly less dose adjustments, and renal function continually needs to be addressed.20 The purpose of this study was to evaluate the use of dabigatran at a community hospital between December 2010 and June 2012 and to identify prescribing areas that can be improved to ensure appropriate use and patient outcomes.     

Ximelagatran: direct thrombin inhibitor

Warfarin sodium is an effective oral anticoagulant drug. However, warfarin has a narrow therapeutic window with significant risks of hemorrhage at therapeutic concentrations. Dosing is difficult and requires frequent monitoring. New oral anticoagulant agents are required to improve current anticoagulant therapy. Furthermore, while warfarin is effective in venous disease, it does not provide more than 60% risk reduction compared with placebo in venous thrombosis prophylaxis and considerably lower risk reduction in terms of arterial thrombosis. Ximelagatran is an oral pro-drug of melagatran, a synthetic small peptidomimetic with direct thrombin inhibitory actions and anticoagulant activity. As an oral agent, ximelagatran has a number of desirable properties including a rapid onset of action, fixed dosing, stable absorption, apparent low potential for medication interactions, and no requirement for monitoring of drug levels or dose adjustment. It has a short plasma elimination half-life of about 4 hours in cases of unexpected hemorrhage or need for reversal. Its main toxicity relates to the development of abnormal liver biochemistry and/or liver dysfunction with "long-term" use of the drug. This usually occurs within the first 6 months of commencing therapy, with a small percentage of patients developing jaundice. The biochemical abnormality usually resolves despite continuation of the drug. The cause of this toxicity remains unknown. Clinical studies to date have shown that ximelagatran is noninferior to warfarin in stroke prevention in patients with nonvalvular atrial fibrillation, noninferior to standard therapy as acute and extended therapy of deep vein thrombosis (DVT), and superior to warfarin for the prevention of venous thromboembolism post-major orthopedic surgery. It has also been shown to be more effective than aspirin alone for prevention of recurrent major cardiovascular events in patients with recent myocardial infarction.     

Detected atrial fibrillation in north Italy: rates, calculated stroke risk and proportion of patients receiving thrombo-prophylaxis

BACKGROUND: Atrial fibrillation (AF) is a major risk factor in the development of ischaemic stroke. The rate of embolic events can be reduced significantly by appropriate therapy. Epidemiological data and information about the attitude of physicians towards prophylaxis of thromboembolism are crucial to determine future strategies to decrease strokes in patients with AF. Unfortunately, these data are unknown in Italy. OBJECTIVES: The aims of this study were to study the prevalence of diagnosed AF in northern Italy, to estimate the percentage of high, moderate and low risk patients and to investigate the pattern of embolic prophylaxis among GPs. METHODS: Fifty-one GPs reviewed all the clinical records of subjects aged >/=40 years and identified those patients with chronic or paroxysmal AF. RESULTS: Among 41 050 patients, 719 [1.75%; 95% confidence interval (CI) 1.59-1.91] had AF (70% chronic, 30% paroxysmal). Only 4% were at low risk for ischaemic stroke, whereas 32% were at moderate and 64% at high risk. Contraindications to antiplatelet or anticoagulant therapy were present in 11% of AF patients. Antithrombotic prophylaxis was underused among the 51 GPs. CONCLUSIONS: Detection of AF could be 30-40% lower than real prevalence and, therefore, adequate evaluation and treatment aimed at avoiding ischaemic stroke could be denied to a great number of Italian patients. AF detection and prophylaxis of thromboembolic risk can be improved among GPs in northern Italy.     

Apixaban for stroke prevention in atrial fibrillation: a review of the clinical trial evidence

The objective of this review is to summarize data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) and Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) trials of apixaban for stroke prevention in patients with atrial fibrillation (AF). The ARISTOTLE trial compared apixaban with warfarin in 18 201 patients with AF and ≥ 1 additional risk factor for stroke. The AVERROES trial compared apixaban with aspirin in 5599 patients with AF who were at increased risk of stroke and for whom vitamin K antagonists were unsuitable. In ARISTOTLE, apixaban reduced the risk of stroke or systemic embolism by 21% compared with warfarin (1.27% vs 1.60% per year; hazard ratio, 0.79; 95% confidence interval, 0.66-0.95). The reduction was significant and demonstrated the superiority of apixaban over warfarin for the primary outcome of preventing stroke or systemic embolism (P = 0.01 for superiority). Apixaban also reduced all-cause mortality by 11% (P = 0.047) and major bleeding by 31% (P < 0.001) compared with warfarin. The benefits of apixaban observed in ARISTOTLE are further supported by the results from AVERROES, which demonstrated a 55% reduction in the risk of stroke or systemic embolism compared with aspirin. Risk of major bleeding was not significantly different between apixaban and aspirin. Subgroup analyses in both trials demonstrated that the effects of apixaban are highly consistent across various patient subpopulations. Discontinuation of study medication was significantly lower with apixaban than with either warfarin in ARISTOTLE or aspirin in AVERROES. Apixaban is the first new oral anticoagulant that has been shown to be superior to warfarin in reducing stroke or systemic embolism, all-cause mortality, and major bleeding in patients with AF. Moreover, in patients with AF who are considered unsuitable for warfarin therapy, apixaban was more effective than aspirin for stroke prevention and had a similar rate of major bleeding.     

Cost-Utility Analysis of Apixaban versus Warfarin in Atrial Fibrillation Patients with Chronic Kidney Disease

Background

Warfarin use for stroke prevention in atrial fibrillation (AF) patients with chronic kidney disease is debated. Apixaban was shown to be safer than warfarin, with superior reduction in the risk of stroke, systemic embolism, mortality, and major bleeding irrespective of kidney function.

El cambio de paradigma en la prevención de ictus en la fibrilación auricular. Retos y oportunidades emergentes para el médico de familia

Atrial fibrillation (AF), is the most prevalent sustained arrhythmia in general population, affecting up to 10% in patients of advanced age. AF doubles overall mortality and increases up to 5–6 times the risk of stroke, which have the characteristic of being particularly harmfull. The basis of treatment on AF are the rhythm or rate control and the prevention of thromboembolism. For the latter purpose the treatments that have been most effective are oral acticoagulants. For decades and until just a few years ago, the only oral drugs available for this purpose have been the anti-vitamin K, mainly represented in our country by acenocoumarol and lesser extent by warfarin. These drugs have been shown to reduce strokes and mortality compared to placebo and with antiplatelet drugs, so have been and continue to be the standard treatment and the comparator for all antithrombotic drugs in patients with AF. The variability in the therapeutic response, their food and drugs interactions and their narrow therapeutic window that entail the need to frequently monitoring, has led to look for new drugs that, at least maintaining their advantages, where able to avoid some of the drawbacks.Currently we have a number of new drugs that meet these premises, although they have the disadvantage of a higher direct cost. The arrival of these new oral anticoagulants (NOAC) make necessary to know them well, reach a consensus for a correct use and to make changes in the clinical management of these patients when they are used.In this article we review the indications and way of use of the different options (classics and news) of antithrombotic therapy in patients with AF, the situation of anticoagulated patients in our country, the characteristics of the NOAC, its recommendations for use and the challenges to that are subjected family physicians regarding these changes.     

Comparison of hospital length of stay between hospitalized non-valvular atrial fibrillation patients treated with either apixaban or warfarin

Background. Hospital length of stay (LOS) is an important cost driver for hospitals and payers alike. Hospitalized non-valvular atrial fibrillation (NVAF) patients treated with apixaban may have shorter LOS than those treated with warfarin because of the absence of need for INR monitoring in apixaban. Thus, this study compared hospital LOS between hospitalized NVAF patients treated with either apixaban or warfarin. Methods. This was a retrospective, observational cohort study based on a large US database including diagnosis, procedure, and drug administration information from >600 acute-care hospitals. Patients selected for study were aged ≥18 years and had a hospitalization record with an ICD-9-CM diagnosis code for atrial fibrillation (AF) in any position from 1 January 2013 to 28 February 2014 (index hospitalization). Patients with diagnoses indicative of rheumatic mitral valvular heart disease or a valve replacement procedure during index hospitalization were excluded. Patients were required to have been treated with either apixaban or warfarin, and not treated with rivaroxaban or dabigatran, during index hospitalization. Apixaban patients were propensity score (PS) matched to warfarin patients at a 1:1 ratio, using patient demographic/clinical and hospital characteristics. The study outcome was hospital LOS, calculated as discharge date minus admission date; a sensitivity analysis calculated hospital LOS as discharge date minus first anticoagulant administration date. Sub-analyses were conducted among patients with a primary diagnosis of AF. Results. The study included 832 apixaban patients matched to 832 warfarin patients. Mean [standard deviation (SD)] and median hospital LOS were significantly (p < 0.001) shorter in apixaban patients (4.5 [4.2] and 3 days) than in warfarin patients (5.4 [5.0] and 4). Results were consistent in the sensitivity and sub-analyses. Conclusions. Among NVAF patients, apixaban treatment was associated with shorter hospital LOS when compared with warfarin treatment. These findings may have important clinical and economic implications for hospitals, payers, and patients.