Prevention of thromboembolism in atrial fibrillation

OBJECTIVE: Appropriate use of drugs to prevent thromboembolism in patients with atrial fibrillation (AF) involves comparing the patient's risk of stroke and risk of hemorrhage. This review summarizes the evidence regarding the efficacy of these medications. METHODS: We conducted a meta-analysis of randomized controlled trials of drugs used to prevent thromboembolism in adults with nonpostoperative AF. Articles were identified through the Cochrane Collaboration's CENTRAL database and MEDLINE until May 1998. MAIN RESULTS: Eleven articles met criteria for inclusion in this review. Warfarin was more efficacious than placebo for primary stroke prevention (aggregate odds ratio [OR] of stroke = 0.30, 95% confidence interval [CI] 0.19, 0.48), with moderate evidence of more major bleeding (OR 1.90; 95% CI 0.89, 4.04). Aspirin was inconclusively more efficacious than placebo for stroke prevention (OR 0.56, 95% CI 0.19, 1.65), with inconclusive evidence regarding more major bleeds (OR 0.81, 95% CI 0.37, 1.77). For primary prevention, assuming a baseline risk of 45 strokes per 1,000 patient-years, warfarin could prevent 30 strokes at the expense of only 6 additional major bleeds. Aspirin could prevent 17 strokes, without increasing major hemorrhage. In direct comparison, there was evidence suggesting fewer strokes among patients on warfarin than among patients on aspirin (aggregate OR 0.64, 95% CI 0.43, 0.96), with only suggestive evidence for more major hemorrhage (OR 1.60, 95% CI 0.77,3.35). However, in younger patients, with a mean age of 65 years, the absolute reduction in stroke rate with warfarin compared with aspirin was low (5.5 per 1,000 person-years) compared with an older group (15 per 1,000 person-years). CONCLUSION: In general, the evidence strongly supports warfarin for patients with AF at average or greater risk of stroke. Aspirin may prove to be useful in subgroups with a low risk of stroke, although this is not definitively supported by the evidence.     

Rapid achievement of therapeutic anticoagulation positively affects outcome in patients undergoing cardioversion for persistent atrial fibrillation

BACKGROUND: Current guidelines recommend anticoagulation with warfarin with documentation of an International Normalized Ratio (INR) of 2-3 for 3 weeks prior to cardioversion of persistent atrial fibrillation (AF). Achievement of adequate anticoagulation often takes longer than 3 weeks, increasing the time to cardioversion. HYPOTHESIS: The goal of the study was to quantify the total time elapsed for adequate anticoagulation and to identify differences in time to cardioversion between patients managed by primary care physicians (PCP) compared with those enrolled in a structured anticoagulation clinic (AC). Finally, we assessed the effect on treatment outcome between groups. METHODS: A retrospective chart review identified those patients undergoing elective cardioversion who were started on warfarin at our medical center since 1997. The venue of anticoagulation management, time for adequate maintenance of INR, and total time to cardioversion were recorded. A comparison was made between the two groups to identify the effect on treatment outcome. Multivariate analysis was performed to evaluate any effect comorbidities may have played on maintenance of normal sinus rhythm (NSR) within the treatment groups. RESULTS: Of 83 patients, 48 had warfarin therapy monitored at their PCP and 35 were managed at our AC. Average time to therapeutic INR at AC and PCP was 29.1 +/- 9.3 and 50.7 +/- 6.8 days, respectively (p = 0.026). Average time to cardioversion at AC and PCP was 60.6 +/- 11.2 and 88.7 +/- 18.5 days (p = 0.041). At 12 months post cardioversion, 30 of 83 patients maintained NSR. Nineteen of 35 patients (54.3%) managed at AC maintained NSR compared with 11 of 48 patients (22.9%) managed at PCP (RR 0.61, 95% confidence interval 0.45-0.84) (p = 0.015). CONCLUSION: Therapeutic anticoagulation is more quickly achieved in a specialty anticoagulation clinic than at a PCP and positively affects therapy outcome.     

Duration of warfarin sodium therapy prior to electrical cardioversion of atrial fibrillation

OBJECTIVES: To evaluate the duration of anticoagulation treatment with warfarin sodium before elective DC-cardioversion and to identify clinical variables predicting short-term versus long-term waiting times. DESIGN: Retrospective. SUBJECTS: Patients with a known start date for warfarin sodium, a known duration of atrial fibrillation (AF) and who underwent DC-cardioversion were included. MAIN OUTCOME MEASURES: Duration of treatment with warfarin sodium prior to DC-cardioversion. METHODS: The hospital records of 288 consecutive patients with AF scheduled for elective cardioversion at two hospitals in Stockholm were reviewed. Only patients with a known start date for warfarin sodium and known duration of AF were included in the study. RESULTS: The median age was 70 (26-85) years and the duration of AF at time of cardioversion were 18 weeks (5-273) weeks. The median treatment duration prior to cardioversion with warfarin sodium was 12 weeks. Sinus rhythm was established in 224 (78%) patients of which 90 (40%) remained in sinus rhythm 1 month after cardioversion. In multivariate analysis, the only independent predictor of short waiting times for cardioversion (8 vs. 15 weeks) was if a cardiologist instituted the treatment with warfarin sodium (P < 0.001, 95% CI 5.0-9.0). CONCLUSION: The average waiting time from start of warfarin sodium treatment to elective cardioversion exceeds by far the recommended 3-4 weeks on therapeutic international normalized ratio (INR). In order to minimize the time period until cardioversion significant changes in the out-of-hospital care logistics has to be undertaken.     

A warfarin induction regimen for out-patient anticoagulation in patients with atrial fibrillation

Currently available protocols for induction of warfarin anticoagulation employ initial doses of 10 mg and are best suited to in-patient use. However, with the increasing number of elderly patients with atrial fibrillation requiring anticoagulation, there is a need for a less intense regimen which could be used for out-patients. We have established such a regimen and report on its prospective evaluation in 37 patients referred for out-patient initiation of warfarin, and a non-randomized comparison with 37 in-patients, with similar diagnoses, commenced on a traditional warfarin protocol. After exclusion of five patients on amiodarone, all of whom experienced supratherapeutic International Normalized Ratio (INR) results, the new out-patient regimen, employing an initial 5 mg dose, resulted in a lower maximum INR during the first 21 d therapy (median 2.9 v 4.0; P  = 0.0001) and fewer INRs > 4.5 (2/36 v 9/33) compared to the traditional 10 mg regimen. Time to reach stable anticoagulation was similar with each regimen; however, the 5 mg regimen gave a more accurate prediction of maintenance dose (correlation coefficient for predicted versus actual maintenance dose, r  = 0.985). In comparison to a traditional 10 mg protocol, the proposed 5 mg warfarin induction regimen proved both safer and more reliable for initiation of prophylactic anticoagulation in patients with atrial fibrillation.     

Stroke prevention in elderly patients with atrial fibrillation: challenges for anticoagulation

Elderly patients with atrial fibrillation (AF), who constitute almost half of all AF patients, are at increased risk of stroke. Anticoagulant therapies, especially vitamin K antagonists (VKA), reduce the risk of stroke in all patients including the elderly but are frequently under-used in older patients. Failure to initiate VKA in elderly AF patients is related to a number of factors, including the limitations of current therapies and the increased risk for major haemorrhage associated with advanced age and anticoagulation therapy. Of particular concern is the risk of intracranial haemorrhages (ICH), which is associated with high rates of mortality and morbidity. Novel oral anticoagulant agents that are easier to use and might offer similar or better levels of stroke prevention with a similar or reduced risk of bleeding should increase the use of antithrombotic therapy in the management of elderly AF patients. Amongst these new agents, the recently approved direct thrombin inhibitor dabigatran provides effective stroke prevention with a significant reduction of ICH, and enables clinicians to tailor the dose according to age and haemorrhagic risk.     

老年心房颤动患者的抗凝策略与抗凝强度评价

房颤是一个严重的临床问题,随着年龄增长,其发病率逐渐增高。房颤所导致的血栓栓塞并发症高,致死、致残率高,未经治疗的房颤患者脑卒中年发生率平均为5%。在临床工作中,年龄是房颤患者血栓栓塞危险分层及指导抗凝策略的重要因素,对75岁以上、肾功能异常、高血压未能良好控制者在抗凝治疗中应加强监测,可考虑适当降低抗凝强度,以防止出血并发症。     

Stroke prophylaxis in institutionalized elderly patients with atrial fibrillation

OBJECTIVES: To identify patterns and predictors of antithrombotic use and to evaluate the appropriateness of antithrombotic therapy for stroke prophylaxis in institutionalized elderly patients with atrial fibrillation. DESIGN: Retrospective study. SETTING: Seventeen long-term care institutions in Edmonton, Alberta. SUBJECTS: Two hundred sixty-five long-term care residents, aged 65 and older, with atrial fibrillation. MEASUREMENTS: The proportion of patients who were prescribed warfarin, acetylsalicylic acid (ASA), both, or neither was determined. Odds ratios were calculated to identify risk factors for stroke and bleeding that are predictive of the receipt of anticoagulant therapy. Appropriateness of therapy was evaluated based on whether patients were prescribed antithrombotic therapy in accordance with their risk factors for stroke and bleeding. RESULTS: Warfarin was prescribed for 49% of patients, ASA for 22%, both for 8%, and neither for 20%. Nearly all patients (97%) were considered to be at high risk for stroke, with age being the predominant risk factor (88%>75), whereas about half were considered to be at low risk for bleeding. Multivariate analyses did not find any associations between individual risk factors for bleeding and anticoagulant treatment, with the exception of recent surgery (odds ratio=0.59, 95% confidence interval=0.37-0.94). Overall, 54.8% of patients received appropriate antithrombotic therapy. Of patients who were optimal candidates for anticoagulation, 60% received appropriate therapy (warfarin with or without ASA). CONCLUSION: Although warfarin was the most appropriate treatment in nearly all of this population at high risk for stroke, it was prescribed in fewer than two-thirds of patients. Antithrombotic therapy was not always prescribed in accordance with patients' risk factors for stroke and bleeding. There is a need for systematic identification of appropriate candidates for anticoagulation in the long-term care setting.     

The decision to anticoagulate: assessing whether benefits outweigh the risks for patients with atrial fibrillation

In a review of relevant articles from the Medline database on stroke risk in atrial fibrillation (AF) and adverse events related to anticoagulation treatment, we found that research to date shows a major potential benefit of warfarin therapy (International Normalized Ratio [INR] 2.0-3.0) for patients with AF (68% risk reduction in primary stroke prevention with warfarin vs. placebo). Despite this highly significant reduction in stroke risk, fewer than 50% of eligible patients are treated, in many cases because of fears of intracranial hemorrhage (ICH). The decision to implement anticoagulant therapy to improve outcome requires balancing the decreased risk for stroke against the increased risk for ICH. Various methods have been developed to define patient-specific stroke risk. In contrast, risk for ICH strongly correlates with the intensity of anticoagulation, which is an unpredictable but controllable variable requiring frequent dose adjustments. Recent studies have also identified subgroups of patients with neurologic pathologies who are at increased risk for ICH. However, when the INR is properly controlled, the benefit from anticoagulation therapy for patients with AF and other risk factors for stroke exceeds the risk for ICH. Careful monitoring of anticoagulation and warfarin dose titration to maintain the INR between 2.0 and 3.0 is critical for reducing the risk for ICH, as is excluding patients with neurologic conditions that increase the likelihood of ICH. Future developments, such as the introduction of oral direct thrombin inhibitors with more predictable pharmacokinetics than warfarin, may further improve the benefit-to-risk ratio of anticoagulation therapy for patients with AF.     

Long-term clinical efficacy and risk of catheter ablation for atrial fibrillation in the elderly

Introduction: The number of elderly patients with atrial fibrillation (AF) is increasing rapidly, and the safety and efficacy of catheter ablation in this demographic group has not been established. Methods: Over a 7‐year period we studied 1,165 consecutive patients undergoing 1,506 AF ablation procedures using a consistent ablation protocol that included proximal ostial pulmonary vein (PV) isolation and focal ablation of non‐PV AF triggers. Outcome was analyzed for three distinct age groups: <65 years (group 1; n = 948 patients), 65–74 years (group 2; n = 185 patients), and ≥75 years (group 3; n = 32 patients) based on the age at the initial procedure. Results: There was no significant difference in AF control (89% in group 1, 84% in group 2, and 86% in group 3, P = NS) during a mean follow‐up of 27 months. Major complication rates were also comparable (1.6% in group 1, 1.7% in group 2, 2.9% in group 3, P = NS) between the three groups. There was no difference in the left atrial size, percentage with left ventricular ejection fraction <50%, or percentage with paroxysmal versus more persistent forms of atrial fibrillation. However, older patients were more likely to be women (20% in group 1, 34% in group 2, and 56% in group 3, P < 0.001) and have hypertension and/or structural heart disease (56% in group 1 vs 68% in group 2 vs 88% in group 3; P < 0.001). There was a strong trend demonstrating that older patients were less likely to undergo repeat ablation (26% vs 27% vs 9%) to achieve AF control and more likely to remain on antiarrhythmic drugs (20% vs 29% vs 37%; P < 0.05). Conclusions: Elderly patients with AF undergoing catheter ablation therapy are represented by a higher proportion of women and have a higher incidence of hypertension/structural heart disease. To achieve a similar level of AF control, there appears to be no increased risk from the ablation procedure, but elderly patients are more likely to remain on antiarrhythmic drugs.     

老年非瓣膜性心房颤动抗凝治疗现状分析

目的分析影响老年非瓣膜性心房颤动患者抗凝治疗的因素,为提高老年心房颤动患者抗凝治疗寻求解决方法。方法对2009-10-01—2010-04-30入住北京协和医院,年龄≥65岁的老年非瓣膜性心房颤动患者进行门诊及电话随访,观察分析全因死亡、抗凝比例、未选择抗凝的原因、抗凝终止的原因、不抗凝(抗凝终止)后的抗栓方法等指标。结果共70例连续入院的患者纳入研究,平均随访9.1个月(6.0~13.5个月)。有效随访63例,其中包括年龄<75岁组33例和年龄≥75岁组30例。失访7例(10%)。随访期间共8例(12.7%)死亡,包括年龄<75岁组1例(3%)和年龄≥75岁组7例(23.3%)。有效随访病例中,进行抗凝治疗的仅16例(25.4%),这16例中INR达标13例。8例死亡患者均未进行抗凝治疗,其中6例称大夫未交待抗凝,另2例有明确抗凝禁忌证。结论老年心房颤动患者抗凝比例低,有效抗凝率低。抗凝过程中中断的比例高。解决老年心房颤动患者抗凝过程的具体困难是有效治疗的关键。     

达比加群酯对非瓣膜性房颤导管消融围术期抗凝疗效和安全性的 Meta 分析

目的：系统评价达比加群酯对非瓣膜性房颤导管消融围术期的抗凝疗效和安全性。方法计算机检索 PubMed、EMbase、The Cochrane Library（2016年第2期）、CMB、知网、万方和维普数据库,搜集有关房颤导管消融围术期使用达比加群酯和华法林抗凝治疗的随机对照及非随机对照的研究文献,由两位评价员独立筛选文献、提取资料和评价纳入研究的偏倚风险后,采用 RevMan 5．3软件进行 Meta 分析。结果最终纳入23个研究、共7673例患者。Meta 分析结果显示：达比加群酯组脑卒中或短暂性脑缺血发生率与华法林组无明显区别[OR ＝1．0,95％CI：0．60～1．68,P ＝0．99],大出血事件发生率无明显区别[OR ＝0．79,95％CI：0．52～1．19, P ＝0．25],小出血事件发生率显著降低[OR ＝0．71,95％CI：0．57～0．87,P ＝0．001]。结论达比加群酯在房颤导管消融围术期抗凝疗效及大出血并发症的发生率上与华法林无明显区别,小出血并发症的发生率较华法林降低。     

Worldwide Management of Oral Anticoagulant Therapy: the ISAM Study

A multicenter, observational, retrospective, cross-sectional study of patients, receiving oral anticoagulation therapy (OAT) for stroke prophylaxis in chronic non-valvular atrial fibrillation (NVAF) was conducted in the US, Canada, France, Italy and Spain according to their predominant model of care [routine medical care (RMC) or Anticoagulation Clinic care (ACC)]. The study objectives were to assess anticoagulation control (time in target range), and to describe the features of the local model of care. Consecutive patients were recruited on the basis of a minimum of 60 days of oral anticoagulant treatment over a 12 month period, and clinic and physician details were captured by means of a structured face-to-face or telephone interview. Time in therapeutic range (TTR) was calculated by using linear interpolation between INR values. A total of 1511 patients were recruited, of whom 1445 were included in the analysis of TTR. TTR was higher in ACC (69.5% and 64.9% for Italy and Spain, respectively) with respect to RMC (58.1%, 62.8% and 59.3% for the US, Canada and France, respectively). Mean intervals between INR determinations were between 3 and 4 weeks. Dose changes in case of INR outside therapeutic range were more frequent in Spain and less frequent in France. Striking differences were observed in type of VKA used, specialists involved in patient management, and dosage instructions. Studying of anticoagulation management based on local models of care highlights important discrepancies among countries and suggests further standardization of the management of this important therapy is necessary.     

Anticoagulation in atrial fibrillation and flutter.

Atrial fibrillation and atrial flutter are important risk factors for stroke. Based on a literature search, pathogenesis of thromboembolism, risk assessment in patients, efficacy of anticoagulation therapy and its alternatives are discussed. Special emphasis is put on issues like paroxysmal atrial fibrillation, atrial flutter and anticoagulation surrounding catheter ablation and cardioversion. A strategy for anticoagulation around the time of pulmonary vein ablation is suggested.     

Pulmonary vein antrum isolation for atrial fibrillation on therapeutic coumadin: special considerations

Pulmonary vein antrum isolation (PVAI) has emerged as an effective treatment for drug-refractory atrial fibrillation (AF). However, thromboembolic events are important complications of this approach. Management of anticoagulation is essential to prevent thromboembolic complications and avoid bleeding complications. The purpose of this review is to outline the general principles followed at our AF centers to address the important issue of pre-, peri-, and postprocedural anticoagulation strategies during PVAI of AF. We initiate warfarin therapy prior to the ablation procedure and continue it through the procedure. Prior work has demonstrated that continuation of therapeutic warfarin during the radiofrequency catheter ablation reduces the risk of periprocedural stroke/transient ischemic attack without increasing the risk of hemorrhagic events. In fact, a strategy that interrupts warfarin anticoagulation may increase the risk of stroke, even with bridging with enoxaparin. Data from our work have shown that minor bleeding was more frequent in the patients bridged with heparin or enoxaparin. There was no significant difference in incidence of major bleeding complications among the patients with a therapeutic level of international normalized ratio (INR) compared with patients for whom bridging therapy was used. Furthermore, the strategy of ablation during a therapeutic INR could be more economical compared with bridging therapy with enoxaparin. Continuation of therapeutic warfarin during ablation of AF may be the best strategy, especially in patients with nonparoxysmal AF, patients with higher thromboembolic risk scores, and patients who require extensive ablation during PVAI of AF.     

Non-rheumatic atrial fibrillation and stroke

The risk of systemic embolism and stroke in patients with non-rheumatic atrial fibrillation (NRAF) should not be underestimated. The annual embolic rate is approximately 5% and in those with left atrial enlargement and/or left ventricular (LV) dysfunction, or who have already had systemic embolism, this rate may be as high as 20%. Decisions on patient management and the prophylaxis of stroke must always be individualised. The risk of bleeding related to warfarin is almost certainly greater than that encountered in the previous randomised trials. Also, clinical and echocardiographic features can further define absolute risk in an individual patient with NRAF. Clinical markers of increased risk of embolism in patients with NRAF include older age, previous cerebral embolism, recent congestive heart failure, hypertension and diabetes mellitus. Transthoracic echocardiography improves risk stratification and should be performed in the vast majority of patients. Embolic risk is greatest in those with increasing left atrial dilation, atrial dysfunction and LV dysfunction. Transoesophageal echocardiography sharpens the risk profile in selected patients. Overall randomised trials show greater benefit with warfarin than aspirin. In general, increasing age is associated with a greater incidence of structural heart disease and probably implies greater potential benefit with warfarin. Increasing age per se may not increase the risk of warfarin-related bleeding. When the decision is made to warfarinise patients, at the present time data suggest that the target INR should be in the range of 2.0–3.0.     

75岁以上老年非瓣膜病心房颤动患者抗血栓治疗的应用现状

目的对于我院>75岁老年非瓣膜病心房颤动(房颤)患者抗血栓药物治疗的情况进行调查,了解用药现状。方法调查>75岁非瓣膜病房颤患者125例,对其危险因素及抗血栓药物使用情况进行分析。结果125例患者中,合并多种危险因素者多见,其中应用华法林者只有30例(24.0%),应用阿司匹林者54例(43.2%),其他抗血小板药物29例(23.2%),未应用抗血栓药物12例(9.6%)。阿司匹林及其他抗血小板口服药剂量为每天75~100 mg。结论>75岁老年非瓣膜病房颤患者华法林应用率低,抗血小板药使用率高,但用药剂量偏小。     

高龄持续性心房纤颤患者不同剂量阿司匹林与华法林抗栓疗效及安全性比较

目的观察在持续性心房纤颤（房颤）的高龄患者中,不同剂量阿司匹林及华法林的疗效和安全性。方法选取年龄≥75岁的持续性房颤患者217例,分为4组,华法林高抗凝组『2．0〈国际标准化比率（international normalized ratio,INR）≤3．0154例,华法林低抗凝组（1．6≤INR≤2．0）53例,阿司匹林组（325mg／d）47例,阿司匹林组（200mg／d）63例,观察各组中血栓栓塞和出血事件的发生率。结果华法林高抗凝组与低抗凝组血栓栓塞发生率明显低于阿司匹林组（325mg／d）,差异有统计学意义（矿=6．487,P=O．011;矿=7．929,P=O．005;r=6．354,P=O．012;r=7．771,P=O．005）;华法林高抗凝组出血发生率明显高于低抗凝组和阿司匹林组（200mg／d）,差异有统计学意义（14.8％＇US．0m0,P〈0．05）;华法林高抗凝组与阿司匹林组（325mg／d）出血发生率比较,差异无统计学意义（P〉O．05）。结论对于年龄≥75岁的老年持续性房颤患者,低抗凝强度华法林（1．6≤INR≤2．0）安全有效,其疗效优于阿司匹林。     

老年非瓣膜病性心房纤颤患者抗血栓治疗现状分析

目的分析空军总医院老年非瓣膜病性心房纤颤（NVAF）患者抗血栓药物治疗现状及未抗凝治疗的原因。方法调查老年NVAF患者109例,对其病因、血栓栓塞危险因素、抗血栓药物应用情况及未应用华法林抗凝治疗原因进行分析。应用CHADS卒中风险评分表对NVAF患者进行血栓栓塞危险评估。结果91.6%患者接受了抗血栓治疗。符合抗凝治疗指征患者68例,仅38.2%接受了华法林治疗,57.4%进行了抗血小板治疗阿司匹林剂量为（87±15）mg/d,4.4%未进行任何抗血栓治疗。而其中NVAF呈阵发性者仅5.0%应用了华法林抗凝治疗。未抗凝治疗者54例,其中存在抗凝禁忌证12例（15.0%）;严重出血而停用1例（1.3%）,不能凝血监测2例（2.5%）;担心出血拒绝8例（10.0%）;阵发性心房纤颤未抗凝治疗20例（25.0%）;冠脉支架术后双重抗血小板治疗而未抗凝治疗3例（3.75%）;原因不明9例（11.3%）。结论老年NVAF患者抗血栓治疗中华法林应用率低,而且阵发性心房纤颤的华法林应用率更低,抗血小板治疗中阿司匹林剂量不足。