Treatment patterns and real-world effectiveness of warfarin in nonvalvular atrial fibrillation within a managed care system

ABSTRACT

Objective: To examine warfarin utilization and clinical effectiveness among patients with nonvalvular atrial fibrillation within usual clinical care in a managed care system.

Research design and methods: A retrospective analysis of health care claims for an approximately four million member managed care organization was performed. Health plan members with a diagnosis of nonvalvular atrial fibrillation in calendar year 2000 were identified and stratified into two cohorts: Warfarin Therapy (newly initiating warfarin) or Warfarin Candidates (eligible for warfarin therapy according to the ACC/AHA/ESC Guidelines for the Management of Patients with Atrial Fibrillation, but did not receive warfarin).

Measurements: The occurrence of thromboembolism, ischemic stroke, and hemorrhage during a maximum 720‐day follow-up were compared between cohorts, adjusting for age, gender, and other risk factors, using Cox regression.

Results: Among 12?539 subjects (mean age 78.0 ± 8.8 years) with nonvalvular atrial fibrillation, 4895 (39.0%) initiated Warfarin Therapy and 7644 (61.0%) were Warfarin Candidates. Event occurrences among Warfarin Therapy vs. Warfarin Candidates were: ischemic stroke, 3.7% vs. 4.5%; any thromboembolism, 7.8% vs. 10.8%; and hemorrhage, 4.4% vs. 4.9%, respectively. Warfarin therapy was not associated with an increased risk for hemorrhage (hazard ratio [HR] = 0.97, 95% confidence interval [CI] = 0.82–1.15), while risks for ischemic stroke and any thromboembolism were significantly reduced, by 22% (HR = 0.78, 95% CI = 0.65–0.93) and 34% (HR = 0.66, 95% CI = 0.59–0.75), respectively.

Conclusions: Within usual clinical care for the managed care population examined, warfarin remains underused despite current guidelines recommending its use in nearly all patients with nonvalvular atrial fibrillation. Although utilization of anticoagulation clinics and INR values attained were unknown in this study, the observed risk reductions for ischemic stroke and thromboembolism were lower than those achieved in clinical trials, while no increased risk for hemorrhage was observed. These findings suggest that warfarin is used conservatively, and dosed cautiously, diminishing the full potential benefit of anticoagulant therapy in patients with nonvalvular atrial fibrillation.     

Effectiveness and safety of direct oral anticoagulants in atrial fibrillation patients switched from vitamin K antagonists: A systematic review and meta‐analysis

A substantial proportion of atrial fibrillation patients initiating direct oral anticoagulants (DOAC) are vitamin K antagonists (VKA)‐experienced, for example switchers from VKA to DOAC. With this study, we aimed to summarize available evidence on the effectiveness and safety of DOAC vs VKA in real‐life VKA‐experienced atrial fibrillation patients. We searched EMBASE, MEDLINE and Cochrane Library systematically for English‐language studies indexed any time before October 2018. We included studies of VKA‐experienced atrial fibrillation patients initiating DOAC therapy, with continued VKA therapy as comparator. Outcomes included arterial thromboembolism and bleeding. When appropriate, meta‐analysis was performed by calculating pooled, weighted and adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Eight cohort studies comparing VKA‐experienced DOAC (dabigatran or rivaroxaban) users with continued VKA users were included. When comparing DOAC to VKA, an increased risk of ischaemic stroke and myocardial infarction was found for dabigatran (pooled aHR of 1.61 [95% CI 1.19‐2.19, I² = 65%] and 1.29 [95% CI 1.10‐1.52, I² = 0%], respectively), but not for rivaroxaban. The use of dabigatran in VKA‐experienced users was associated with an increased risk of gastrointestinal bleeding (pooled aHR 1.63 [95% CI 1.36‐1.94, I² = 30%]), but a decreased risk of intracranial bleeding (pooled aHR 0.45 [95% CI 0.32‐0.64, I² = 0%]). In conclusion, the use of dabigatran in prior VKA users in clinical practice was associated with a slightly increased risk of arterial thromboembolism and gastrointestinal bleeding, but a decreased risk of intracranial bleeding. Importantly, observational studies of real‐life VKA‐experienced oral anticoagulant users may be confounded by the reason for switching.     

新型口服抗凝药物的安全性

新型抗凝药物主要包括直接凝血酶抑制剂和Xa因子抑制剂。其中,直接凝血酶抑制剂达比加群酯口服制剂、直接Xa因子抑制剂利伐沙班和阿哌沙班口服制剂已在我国上市;另外一种直接Xa因子抑制剂贝曲沙班口服制剂也正在进行Ⅲ期临床研究;而直接Xa因子抑制剂爱多沙班口服制剂已在日本上市。达比加群酯致颅内出血发生风险低于华法林,但该药可能增加急性冠状动脉综合征患者严重出血和具有临床意义轻度出血的发生率,以及心肌梗死或急性冠状动脉综合征的发生风险。利伐沙班在预防非瓣膜性心房颤动所致脑卒中和栓塞方面优于华法林,预防骨科术后血栓效果优于依诺肝素,大出血事件发生风险与两药相似,而颅内出血发生风险低于华法林。阿哌沙班在降低心房颤动患者脑卒中或全身性栓塞发生率及病死率方面优于华法林,颅内出血发生率低于华法林,大出血发生率与华法林相似或降低;阿哌沙班的安全性与用药剂量相关。爱多沙班的主要不良反应为出血,用于心房颤动患者的有效性及安全性均优于华法林。贝曲沙班用于全膝关节置换术后预防血栓效果与依诺肝素相似,出血发生率低于依诺肝素。     

Treatment patterns and real-world effectiveness of warfarin in nonvalvular atrial fibrillation within a managed care system

OBJECTIVE: To examine warfarin utilization and clinical effectiveness among patients with nonvalvular atrial fibrillation within usual clinical care in a managed care system.Research design and methods: A retrospective analysis of health care claims for an approximately four million member managed care organization was performed. Health plan members with a diagnosis of nonvalvular atrial fibrillation in calendar year 2000 were identified and stratified into two cohorts: Warfarin Therapy (newly initiating warfarin) or Warfarin Candidates (eligible for warfarin therapy according to the ACC/AHA/ESC Guidelines for the Management of Patients with Atrial Fibrillation, but did not receive warfarin). MEASUREMENTS: The occurrence of thromboembolism, ischemic stroke, and hemorrhage during a maximum 720-day follow-up were compared between cohorts, adjusting for age, gender, and other risk factors, using Cox regression. RESULTS: Among 12 539 subjects (mean age 78.0 +/- 8.8 years) with nonvalvular atrial fibrillation, 4895 (39.0%) initiated Warfarin Therapy and 7644 (61.0%) were Warfarin Candidates. Event occurrences among Warfarin Therapy vs. Warfarin Candidates were: ischemic stroke, 3.7% vs. 4.5%; any thromboembolism, 7.8% vs. 10.8%; and hemorrhage, 4.4% vs. 4.9%, respectively. Warfarin therapy was not associated with an increased risk for hemorrhage (hazard ratio [HR] = 0.97, 95% confidence interval [CI] = 0.82-1.15), while risks for ischemic stroke and any thromboembolism were significantly reduced, by 22% (HR = 0.78, 95% CI = 0.65-0.93) and 34% (HR = 0.66, 95% CI = 0.59-0.75), respectively. CONCLUSIONS: Within usual clinical care for the managed care population examined, warfarin remains underused despite current guidelines recommending its use in nearly all patients with nonvalvular atrial fibrillation. Although utilization of anticoagulation clinics and INR values attained were unknown in this study, the observed risk reductions for ischemic stroke and thromboembolism were lower than those achieved in clinical trials, while no increased risk for hemorrhage was observed. These findings suggest that warfarin is used conservatively, and dosed cautiously, diminishing the full potential benefit of anticoagulant therapy in patients with nonvalvular atrial fibrillation.     

More light at the end of the tunnel – apixaban in atrial fibrillation

Introduction: Subjects with atrial fibrillation are at risk of thromboembolic events. The vitamin K antagonists (e.g., warfarin) are useful at preventing coagulation in atrial fibrillation, but are difficult to use. One of the FXa inhibitors, oral apixaban, has been tested as an anticoagulant in atrial fibrillation.

Areas covered: In ARISTOTLE (Apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation) apixaban was compared to warfarin in subjects with atrial fibrillation, and shown to cause a lower rate of stroke or systemic embolism and of major bleeding, than warfarin. In the AVERROES (Apixaban versus acetylsalicylic acid [ASA] to prevent stroke in atrial fibrillations patients who have failed or are unsuitable for vitamin K antagonist treatment) trial, stroke or systemic embolism occurred less often with apixaban than aspirin, whereas the occurrence of major bleeding was similar in the groups.

Expert opinion: Apixaban is much easier for subjects with atrial fibrillation to use than warfarin, as it does not require regular monitoring by a health professional, with dosage adjustment. In addition to replacing warfarin in subjects with atrial fibrillation who are unable or not prepared to use warfarin, apixaban has the potential to replace warfarin more widely in the prevention of thromboembolism in subjects with atrial fibrillation.     

观察华法林及阿司匹林分别对非瓣膜性心房颤动患者血栓栓塞的影响

目的观察华法林及阿司匹林对非瓣膜性心房颤动患者血栓栓塞事件的影响。方法80例非瓣膜性心房颤动患者分为华法林组及阿司匹林组,阿司匹林组每天服用阿司匹林100 mg,华法林组根据国际标准化比值(INR)调整华法林用量,随访时间为2 a。结果阿司匹林组死亡2例,1例为缺血性卒中,另1例为心力衰竭;华法林组1例为猝死。阿司匹林组发生栓塞事件共8例,出血并发症3例;华法林组发生栓塞事件共3例,出血并发症7例。结论华法林可明显降低非瓣膜性房颤患者血栓栓塞事件,但出血并发症稍增多,关键是要严密随访INR。     

Non-vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Patients with Atrial Fibrillation and Liver Disease: A Meta-Analysis and Systematic Review

Background

The effect of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) and liver disease remains largely unresolved. Therefore, we performed a meta-analysis to compare the efficacy and safety of NOACs with warfarin in this population.

Methods

We systematically searched the Cochrane Library, PubMed, and Embase databases for studies reporting the comparisons of NOACs with warfarin in patients with AF and liver disease. A random-effects model was selected to pool the risk ratios (RRs) and 95% confidence intervals (CIs).

Results

A total of six studies with 41,954 participants were included in this meta-analysis. In AF patients with liver disease, compared with warfarin use, the use of NOACs was associated with reduced risks of all-cause death (RR 0.78, 95% CI 0.66–0.93), major bleeding (RR 0.68, 95% CI 0.53–0.88), and intracranial hemorrhage (RR 0.49, 95% CI 0.41–0.59), but had comparable risks of stroke or system embolism (RR 0.80, 95% CI 0.57–1.12) and gastrointestinal bleeding (RR 0.90, 95% CI 0.61–1.34). In AF patients with cirrhosis, NOACs significantly reduced the risks of major bleeding (RR 0.53, 95% CI 0.37–0.76), gastrointestinal bleeding (RR 0.57, 95% CI 0.38–0.84), and intracranial hemorrhage (RR 0.55, 95% CI 0.31–0.97) compared with warfarin.

Conclusions

Based on current publications, the use of NOACs is at least non-inferior to warfarin in patients with AF and liver disease.

     

Treatment Changes among Users of Non‐Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation

Patients with atrial fibrillation discontinuing anticoagulant therapy are left unprotected against ischaemic stroke. Further, switching between oral anticoagulants may be associated with a transiently increased risk of bleeding or thromboembolism. However, there is a paucity of real‐life data on pattern of switching and discontinuation of oral anticoagulants. To address this, we conducted a nationwide drug utilization study including all registered Danish atrial fibrillation patients initiating a non‐VKA oral anticoagulant (NOAC) between August 2011 and February 2016. We assessed changes in anticoagulant treatment, including switching between oral anticoagulants and discontinuation of NOACs, and explored patient characteristics predicting these changes. We identified 50,632 patients with atrial fibrillation initiating NOAC therapy within the study period. The majority initiated dabigatran (49.9%) and one‐third had previously used VKA. Within 1 year, 10.1% switched to VKA, 4.8% switched to another NOAC and 14.4% discontinued treatment. The frequencies of switching to VKA and discontinuation were highest among NOAC users of young age (<55 years) and with low CHA₂DS₂‐VASc score (=0). However, the majority of patients (87.3%) stopping NOAC treatment had a CHA₂DS₂‐VASc score ≥1. We conclude that switching from VKA to NOAC, and to a lesser extent from NOAC to VKA, is common, as is early treatment discontinuation. The majority of treatment changes are observed in patients at increased risk of stroke. More research is warranted on the risks of bleeding and thromboembolism associated with switching and discontinuation of NOACs as well as the underlying reasons why these treatment changes occur.     

An update on the pharmaceutical management of thrombosis

Introduction: Anticoagulants such as heparins and vitamin K antagonists (VKA) are effective for thrombosis prevention and treatment, but are associated with the risk of bleeding and other limitations, spurring the search for improved drugs.

Areas covered: to evaluate the newer anticoagulants, focusing on those tested in phase III clinical trials such as direct oral anticoagulants (DOACs), antisense oligonucleotides (ASO) and warfarin analogues. DOACs such as dabigatran, rivaroxaban, apixaban and edoxaban are licensed for stroke prevention in atrial fibrillation and treatment of venous thromboembolism, dabigatran, rivaroxaban and apixaban for postoperative thromboprophylaxis in patients undergoing elective hip or knee arthroplasty and rivaroxaban for secondary prevention of acute coronary syndromes. ASO interfering with Factor XI hepatic synthesis were effective and safe for thromboprophylaxis in elective knee arthroplasty.

Expert opinion: DOACs have overcome some limitations of anticoagulants such as VKA, but are still associated with a risk of bleeding and they lack both standardized and widely available tests measuring their anticoagulant effect and a reversal agent, except for idarucizumab, specific for dabigatran, in case of major or life threatening bleeding or emergency surgery. Agents targeting Factor XI and possibly Factor XII may be ideal anticoagulants, as they can prevent thrombosis with low bleeding risk.     

Dabigatran etexilate,a new oral direct thrombin inhibitor,for stroke prevention in patients with atrial fibrillation

Importance of the field: Warfarin is the only oral anticoagulant recommended for the prevention of ischemic stroke in atrial fibrillation. A newer and safer anticoagulant is needed because of increased hemorrhagic risks with warfarin, difficult-to-maintain therapeutic levels, and higher drug to drug and food interactions.

Areas covered in this review: Dabigatran etexilate is a new, effective, reversible, rapid-acting, oral direct inhibitor of thrombin. This review focuses on the results of major Phase II and III trials conducted to evaluate the use of dabigatran in prevention of stroke in atrial fibrillation.

What the reader will gain: The objective of this paper is to discuss the use of dabigatran for prevention of stroke in patients with atrial fibrillation and to review its major advantages and disadvantages over warfarin.

Take home message: After the recent publication of Phase III trial RE-LY (randomized evaluation of long-term anticoagulation therapy), the use of dabigatran in atrial fibrillation is more clearly defined. A higher dose of dabigatran may be beneficial in patients who have recurrent ischemic events, despite therapeutic levels of warfarin. A lower dose is potentially safer than warfarin because of fewer hemorrhagic complications. Disadvantages include twice-daily dosing, dyspepsia and higher cost.     

利伐沙班治疗老年非瓣膜性心房颤动患者的有效性及安全性分析

目的探讨老年非瓣膜性心房颤动患者采用利伐沙班治疗的有效性及安全性。方法60例老年非瓣膜性心房颤动患者,依据抗凝治疗方法不同分为利伐沙班组和华法林组,各30例。利伐沙班组患者接受利伐沙班抗凝治疗,华法林组患者接受华法林抗凝治疗。比较两组患者的栓塞事件、出血事件、不良反应发生情况。结果利伐沙班组患者的栓塞事件发生率为10.0%(3/30),华法林组患者的栓塞事件发生率为13.3%(4/30),两组比较差异无统计学意义(P>0.05)。利伐沙班组患者的出血事件发生率为3.3%,低于华法林组的20.0%,差异具有统计学意义(P<0.05)。利伐沙班组患者的不良反应发生率为16.7%,低于华法林组的40.0%,差异具有统计学意义(P<0.05)。结论老年非瓣膜性心房颤动患者采用利伐沙班抗凝治疗的有效性及安全性较华法林高,更能有效降低患者的出血事件、不良反应发生率,值得推广。     

Risk-benefit assessment of anticoagulant therapy

Thromboembolic disease is a common medical condition which, if untreated, carries a significant risk of morbidity and mortality. Treatment with anticoagulant therapy, while clearly beneficial, may expose patients to potentially serious side effects. A thoughtful risk-benefit assessment is therefore crucial before initiating therapy. Thromboembolic disease involves syndromes of both the venous and arterial circulation, and its pathogenesis is best understood by considering the elements of Virchow's Triad. This model defines the risk factors for venous thromboembolism and allows us to classify surgical and medical patients into low, moderate and high risk groups. Similar analysis allows risk assessment for patients prone to cardiogenic embolism resulting from nonvalvular atrial fibrillation, ischaemic heart disease, rheumatic heart disease and valvular prostheses. All anticoagulant therapy is prophylactic. Primary prophylaxis involves instituting anticoagulant therapy in patients at risk, before thromboembolism occurs, while secondary prophylaxis involves treating patients with established disease. The 2 major anticoagulants, heparin and warfarin, differ in their mechanism of action, mode of administration and methods of monitoring. Either may be used as primary or secondary prophylaxis. Heparin, because it acts immediately, is the drug of choice for the short term treatment of thromboembolic disease. Warfarin is the drug of choice for long term oral maintenance therapy. The principal complication of heparin therapy is haemorrhage, although thrombocytopenia and osteoporosis may also occur; the complications of warfarin include haemorrhage and skin necrosis. The risks of complications vary with the underlying thromboembolic disease. After the benefits of treatment are weighed against the risks of complications, recommendations for therapy can be established. The use of anticoagulants in pregnancy is especially complex. Here heparin is probably the preferred agent since, unlike warfarin, it does not cross the placenta and is nonteratogenic.     

The evolving role of dabigatran etexilate in clinical practice

Introduction: Stroke and venous thromboembolism (VTE) affect millions of patients. The vitamin K antagonist, warfarin, has been the main oral anticoagulant used to treat these conditions despite many limitations associated with its use. Recently, multiple novel oral anticoagulants have been approved and are reshaping how patients with atrial fibrillation (AF) at risk of stroke and patients with VTE are treated. The direct thrombin inhibitor, dabigatran etexilate, is among these novel agents that have been developed to overcome limitations with warfarin.

Areas covered: In this article, authors describe the pharmacokinetic and pharmacodynamic properties of dabigatran etexilate and summarize the clinical evidence and controversy surrounding its use in the US, Canada and Europe.

Expert opinion: Dabigatran has demonstrated similar efficacy and safety to enoxaparin for VTE prevention in patients undergoing hip and knee arthroplasty, and to warfarin for the treatment of VTE. Dabigatran (110 mg) is noninferior and dabigatran (150 mg) is superior to warfarin for stroke prevention in patients with nonvalvular AF, with a lower rate of intracranial hemorrhage reported at both doses. Apixaban, rivaroxaban and edoxaban provide alternate anticoagulant options to dabigatran. While there are many similarities, there are also significant differences to consider in agent selection based on patient-specific characteristics.     

Adverse clinical events in Japanese atrial fibrillation patients with and without coronary artery disease—findings from the SAKURA AF Registry

Abstract

Background: Although atrial fibrillation (AF) and coronary artery disease (CAD) are increasing in prevalence in Japan, real-world data regarding clinical outcomes in Japanese AF patients with CAD are limited.

Methods: The SAKURA AF Registry is a prospective multi-center registry created to investigate outcomes of oral anticoagulant (OAC) use in Japanese AF patients. A study was conducted involving 3237 enrollees from 63 Tokyo-area institutions who were followed up for a median of 39.3?months. Clinical adverse events were compared between the patients accompanied with (n?=?312) and without CAD (n?=?2925).

Results: The incidence of cardiovascular events and all-cause mortality rates were significantly higher among patients with CAD than among those without CAD (5.98 vs 2.52 events per 100 patient-years, respectively, p?<?0.001; 3.27 vs 1.94 deaths per 100 patient-years, respectively, p?=?0.012), but there was no difference in strokes/transient ischemic attacks or systemic embolisms (1.70 vs 1.34). After a multivariate adjustment, CAD remained a risk factor for cardiovascular events (hazard ratio [HR]?=?1.57, 95% confidence interval [CI]?=?1.08–2.25, p?=?0.018). Among CAD patients, the propensity score-adjusted risk for major bleeding was significantly decreased among direct oral anticoagulant (DOAC) users in comparison to that among warfarin users (HR?=?0.29, 95% CI?=?0.07–0.94, p?=?0.04), but other adverse clinical events did not differ significantly between these two groups.

Conclusions: CAD did not appear to be a major determinant of strokes/TIAs, major bleeding, or all-cause mortality, but appeared to increase the risk of cardiovascular events in Japanese AF patients. The risk of major bleeding in CAD patients appeared to decrease when a DOAC rather than warfarin was administered. The data suggested that patients with AF and concomitant CAD require careful management and follow-up to reduce cardiovascular risks, and DOACs may be a better choice over warfarin when considering the risk of major bleeding.     

Risk of stroke/systemic embolism,major bleeding and associated costs in non-valvular atrial fibrillation patients who initiated apixaban,dabigatran or rivaroxaban compared with warfarin in the United States Medicare population

Objective: To compare the risk and cost of stroke/systemic embolism (SE) and major bleeding between each direct oral anticoagulant (DOAC) and warfarin among non-valvular atrial fibrillation (NVAF) patients.

Methods: Patients (≥65 years) initiating warfarin or DOACs (apixaban, rivaroxaban, and dabigatran) were selected from the Medicare database from 1 January 2013 to 31 December 2014. Patients initiating each DOAC were matched 1:1 to warfarin patients using propensity score matching to balance demographics and clinical characteristics. Cox proportional hazards models were used to estimate the risks of stroke/SE and major bleeding of each DOAC vs. warfarin. Two-part models were used to compare the stroke/SE- and major-bleeding-related medical costs between matched cohorts.

Results: Of the 186,132 eligible patients, 20,803 apixaban–warfarin pairs, 52,476 rivaroxaban–warfarin pairs, and 16,731 dabigatran–warfarin pairs were matched. Apixaban (hazard ratio [HR]?=?0.40; 95% confidence interval [CI] 0.31, 0.53) and rivaroxaban (HR?=?0.72; 95% CI 0.63, 0.83) were significantly associated with lower risk of stroke/SE compared to warfarin. Apixaban (HR?=?0.51; 95% CI 0.44, 0.58) and dabigatran (HR?=?0.79; 95% CI 0.69, 0.91) were significantly associated with lower risk of major bleeding; rivaroxaban (HR?=?1.17; 95% CI 1.10, 1.26) was significantly associated with higher risk of major bleeding compared to warfarin. Compared to warfarin, apixaban ($63 vs. $131) and rivaroxaban ($93 vs. $139) had significantly lower stroke/SE-related medical costs; apixaban ($292 vs. $529) and dabigatran ($369 vs. $450) had significantly lower major bleeding-related medical costs.

Conclusions: Among the DOACs in the study, only apixaban is associated with a significantly lower risk of stroke/SE and major bleeding and lower related medical costs compared to warfarin.     

房颤合并肝硬化患者的口服抗凝药物选择及抗栓策略研究

目的 探讨房颤合并肝硬化患者临床治疗中口服抗凝药物的选择及安全性。方法 在1例房颤合并乙型肝炎肝硬化患者房间隔修补术后抗栓方案的制定中,通过查阅指南和文献,总结、分析房颤合并肝硬化患者口服抗凝药物的疗效及安全性评价现状。结果 通过综合评估患者情况,停用华法林,予达比加群酯110 mg,bid,联合氯吡格雷75 mg,qd抗栓6个月,之后达比加群酯110 mg,bid长期抗凝治疗。结论 房颤合并肝硬化患者抗栓治疗,应充分评估血栓及出血风险,制定个体化的抗栓策略。房颤合并Child-Pugh A级肝硬化,新型口服抗凝药均可使用;合并Child-Pugh C级肝硬化,口服抗凝剂均不建议使用;合并Child-Pugh B级肝硬化,出血风险高的患者长期抗凝治疗中可选用小剂量达比加群酯。     

临床药师参与1例房颤伴消化道出血的5年追踪治疗分析

目的 为房颤伴高出血风险患者的药学监护提供参考.方法 跟踪随访1例房颤伴消化道出血又新发脑梗死患者5年,从房颤并消化道出血的抗凝方案、新发脑梗死的原因、左心耳封堵术后抗凝3个方面提出药学方案,并实施全程药学监护.结果 治疗期间,患者发生房颤伴消化道出血及腹泻,降低了华法林的抗凝强度,停用低分子肝素,诱发了脑梗死;病情稳...     

The factor xa inhibitor edoxaban for the prevention of stroke and systemic embolism in patients with atrial fibrillation

Introduction: With the rising prevalence of nonvalvular atrial fibrillation (NVAF) in the general population, the development of new drugs for prevention of thromboembolic events is essential. Non-vitamin K antagonist oral anticoagulants (NOACs) have been shown to present a number of advantages over conventionally used agents, such as predictable pharmacokinetics and no requirement for continuous anticoagulant monitoring. The most recently approved NOAC for the NVAF indication is edoxaban. Several subgroup analyses from the edoxaban phase III ENGAGE AF-TIMI 48 trial have now been published, alongside meta-analysis data comparing the four currently approved NOACs. Consequently, an updated review of the literature is merited.

Areas covered: A PubMed search using the terms ‘edoxaban’, ‘non-vitamin K antagonist oral anticoagulant’, ‘ENGAGE AF-TIMI 48’, and ‘atrial fibrillation’ was performed and results screened for the most relevant English language publications. The market position, pharmacological profile, clinical efficacy, safety and tolerability of edoxaban are presented and discussed.

Expert commentary: Edoxaban has been shown to have an efficacy similar or superior to that of warfarin, with a potentially lower risk of major bleeding and predictable, dose-dependent pharmacology. In order to clarify its position within the NOAC market, head-to-head comparative studies are required.     

Clinical potential of oral direct thrombin inhibitors in the prevention and treatment of venous thromboembolism

Current antithrombotic therapies are associated with various practical limitations and risks that restrict their utility in the management of venous thromboembolism. The coagulation factor, thrombin, has been the focus of extensive investigation as a pharmacological target in efforts to improve the management of venous thromboembolism. Hirudin, desirudin, bivalirudin and argatroban are direct thrombin inhibitors that have been launched for limited indications as anticoagulants. Their usefulness for long-term prophylaxis is limited by a requirement for parenteral administration, restricted licensing and bleeding/tolerability profile. Ximelagatran--which, after oral administration, is rapidly converted to its active form, melagatran--is the first oral direct thrombin inhibitor and the first new oral anticoagulant to become available in 60 years. Clinical studies have shown that melagatran/ximelagatran, without coagulation monitoring, is effective and well tolerated for the prevention of venous thromboembolism after hip replacement and knee replacement surgery. Ximelagatran is also effective in the acute treatment of venous thromboembolism and long-term secondary prevention of recurrent venous thromboembolism, the prevention of stroke in patients with atrial fibrillation and in the prevention of cardiovascular events after myocardial infarction. Oral direct thrombin inhibitors have a promising role in the management of venous thromboembolism and other associated medical conditions.     

新型口服抗凝药在非瓣膜性房颤合并脑血管病中的研究进展

抗凝治疗被认为是非瓣膜性心房颤动(房颤)患者缺血性卒中预防策略的基石。新型口服抗凝药相较于传统口服抗凝药华法林, 具有起效快、半衰期短、药物相互作用少以及无需频繁监测凝血指标等优点, 被普遍应用于预防治疗中, 大幅降低了非瓣膜性房颤患者缺血性卒中的发生风险。但对于合并颅内动脉粥样硬化狭窄、急性缺血性卒中、颅内出血、颅内微出血等增加卒中及出血风险的非瓣膜性房颤患者, 临床抗凝治疗及启动时间的选择无疑是个挑战。本文将对新型口服抗凝药在合并常见脑血管病的非瓣膜性房颤患者中的应用进行综述, 为临床治疗与预防提供参考。