Atrial Fibrillation and Anticoagulation in Patients with Permanent Pacemakers: Implications for Stroke Prevention

Several large prospective randomized trials have demonstrated that anticoagulation with warfarin reduces the risk of thromboembolic stroke in high risk patients with chronic AF by approximately 70%. Large numbers of patients with permanent pacemakers have AF, and anticoagulation rates in this population have not been described. In a prospective analysis of 110 consecutive patients attending the pacemaker clinic of a large university hospital, we assessed the number of patients with AF and the proportion of these patients who were receiving anticoagulation to prevent thromboembolic stroke. Where necessary, temporary pacemaker reprogramming to low ventricular rates was utilized to facilitate the diagnosis of AF. Fifty-three of the 110 patients (48%) were diagnosed with AF, all of whom (100%) had accepted high risk factors for thromboembolic stroke. Only eight of the 53 (15%) had been anticoagulated with warfarin. Thirty-six of the 53 patients (68%) diagnosed with AF had no prior documented diagnosis of chronic AF, and the majority had no symptoms suggesting AF. A single lead II ECG was insufficient in 67 of the 110 patients (61%) to diagnose the underlying atrial rhythm; the remainder required 12-lead ECGs or temporary pacemaker reprogramming to low ventricular rates to diagnose the underlying atrial rhythm. AF is common in patients with permanent pacemakers. It is commonly asymptomatic, and anticoagulation is markedly underutilized in reducing stroke risk in these patients. Attention to the possibility of AF in paced patients should allow prompt diagnosis and allow both the initiation of anticoagulation in order to reduce thromboembolic stroke risk and consideration for cardioversion of AF to sinus rhythm.     

非瓣膜性房颤患者的左心耳特点分析

目的：分析非瓣膜性房颤患者左心耳入口内径、左心耳长度及左心耳射血速率的特点。方法：以我院收治的237例房颤患者为研究对象,回顾性分析阵发性房颤与持续性房颤患者左心耳入口内径、长度及左心耳射血速率的差异,并分析房颤患者左心耳入口内径、长度及射血速率的临床相关因素。结果：与阵发性房颤组相比,持续性房颤组左心耳入口内径显著增大,具有统计学意义（P<0.05）,而两组患者的左心耳长度及左心耳射血速率无统计学差异。Spearman相关分析显示左心耳入口内径与身高、房颤病史长短、左房前后径、左室收缩末内径（left ventricular end-systolic diameter LVESD）、左室舒张末内径（left ventricular end-diastolic diameter LVEDD）呈正相关（P<0.05）,与左室射血分数（left ventricular ejection fraction LVEF)呈负相关（P<0.05）;左心耳长度与左房前后径、LVESD、LVEDD呈正相关（P<0.05）,与LVEF呈负相关(P<0.05);左心耳射血速率与年龄、房颤病史长短、左房前后径、LVESD呈负相关（P<0.05）,与LVEF呈正相关(P<0.05)。结论：持续性房颤患者左心耳入口内径大于阵发性房颤患者,左心耳的入口内径、长度、射血速率与多种因素相关。     

Warfarin Use and Stroke Risk Among Patients With Nonvalvular Atrial Fibrillation in a Large Managed Care Population

Background

Stroke prevention is a goal of atrial fibrillation (AF) management, but discontinuation of warfarin anticoagulation therapy is common.

Objective

To investigate the association between warfarin discontinuation and hospitalization for stroke among nonvalvular AF (NVAF) patients enrolled in managed care.

Methods

Patients with NVAF who initiated warfarin therapy from January 2005 through June 2009 were included. Warfarin discontinuation was defined as a supply gap >60 days without evidence of International Normalized Ratio measurements. Follow-up, which was a variable time period from warfarin initiation until the earlier of death, disenrollment from the health plan, or June 30, 2010, was divided into periods of warfarin treatment and discontinuation. Stroke events were identified based on claims for inpatient stays with a primary diagnosis of stroke or transient ischemic attack. Cox proportional hazards models were constructed to assess the relationship between warfarin discontinuation and incident stroke while adjusting for baseline demographics, stroke and bleeding risk, and comorbidities, as well as time-dependent antiplatelet use, stroke, and bleeding events in the previous warfarin treatment period.

Results

Among warfarin initiators with NVAF (N = 16,253), 51.4% discontinued warfarin therapy at least once during a mean follow-up of 668 days. Stroke risk was significantly greater during warfarin discontinuation periods compared with therapy periods (hazard ratio = 1.60; 95% CI, 1.35–1.90; P < 0.001).

Conclusions

More than half of patients on warfarin had treatment gaps or discontinued therapy. Therapy gaps were associated with increased stroke risk.     

Vitamin K Antagonist Treatment in Patients With Atrial Fibrillation and Time in Therapeutic Range in Four European Countries

Purpose

Patients with atrial fibrillation are at increased risk for stroke and thus require anticoagulant prophylaxis with vitamin K antagonists. However, many such patients fail to achieve target coagulation status. The objective of this study was to evaluate time in the therapeutic range and its relationship to clinical outcomes in patients with nonvalvular atrial fibrillation prescribed a vitamin K antagonist in everyday clinical practice in 4 European countries (France, Germany, Italy and the United Kingdom).

Methods

Data were extracted from the European electronic primary care database, the Longitudinal Patient Database. Included in the analysis were 6250 adult patients for whom data on monitoring of coagulation time and international normalized ratio were available. The time within the therapeutic range was estimated by using the Rosendaal method. Patients spending >70% of time within the therapeutic range were considered to have well-controlled treatment. Data on stroke and bleeding events occurring during the study period were taken from patient records. Stroke risk was calculated by using the CHA₂DS₂-VASc score (i.e. 2 points for a history of stroke or TIA and age >75years, and 1 point for age between 65 and 74 years, hypertension, diabetes mellitus, a recent cardiac failure, vascular disease and female sex).

Findings

The proportion of patients with poorly controlled treatment varied from 34.6% in the United Kingdom to 55.8% in Germany. The incidence of stroke was 0.5/100 person-years in well-controlled patients, compared with 1.0/100 in poorly controlled patients. After adjustment for stroke risk factors, the odds ratio was 1.38 (95% CI, 0.93–2.06; P = 0.110). The incidence of hemorrhage was 1.1 and 1.3 events/100 person-years, respectively (odds ratio, 0.91 [95% CI, 0.72–1.16]).

Implications

Many patients receiving prophylaxis with vitamin K antagonists in everyday community care have poorly controlled anticoagulation treatment with vitamin K antagonists. Their international normalized ratio is frequently outside the therapeutic range, and they are thus exposed to an unnecessary risk of stroke or bleeding complications.     

非瓣膜病性房颤伴缺血性中风的二级预防

目的：观察应用阿司匹林预防非瓣膜病性房颤伴缺血性中风患者复发的疗效。方法：选取89例非瓣膜病性房颤伴缺血性中风的患者,随机分为两组,其中阿司匹林组47例,丹参对照组42例,随访1年,观察阿司匹林及丹参片对其复发率病死率及其他血管事件发生率的影响。结果：对照组中风后1年的复发率高于阿司匹林组（P〈0.05）;对照组中风后1年的病死率与其他血管事件的发生率高于阿司匹林组,但差异无统计学意义（P〉0.05）。结论：阿司匹林对非瓣膜病性房颤伴缺血性中风患者有预防复发的作用。     

AUDITS: Mnemonical Approach for Atrial Fibrillation With Coronary Artery Disease

Managing anticoagulation therapy in patients with acute coronary syndrome and atrial fibrillation requires effective use of risk stratification scores to optimize treatment options while weighing the risk of stroke or systemic thromboembolism vs the risk of bleeding. A mnemonic-based clinical practice pathway is proposed to provide nurse practitioners with a structured approach to managing patients with atrial fibrillation in the context of an acute coronary syndrome. The AUDITS mnemonic represents a simplified treatment guide derived from current guidelines and aims to help nurse practitioners implement best practices to ensure patient safety.     

Bleeding as an Outcome Among Patients With Nonvalvular Atrial Fibrillation in a Large Managed Care Population

Background

Patients with nonvalvular atrial fibrillation (NVAF) are at increased risk for stroke and bleeding events, but bleeding as an outcome has not been extensively studied in this patient population.

Objectives

The goal of this study was to estimate the incidence of bleeding events among patients with NVAF enrolled in managed care, investigate the relationships between bleeding incidence and bleeding and stroke risks, and estimate health care costs for patients who had a major bleeding event.

Methods

Adults with commercial insurance or Medicare Advantage coverage and health care claims related to AF between January 2005 and June 2009 but with no evidence of valvular disease were included in this retrospective claims data analysis. Baseline stroke risk (CHADS₂ [Congestive Heart Failure, Hypertension, Age >75 Years, Diabetes Mellitus, and Prior Stroke or Transient Ischemic Attack]) and bleeding risk (HAS-BLED [Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile International Normalized Ratios, Elderly, Drugs/Alcohol]) were estimated. Bleeding events were identified during the variable follow-up period, which lasted from the date of the first qualifying AF visit until the earlier of death, disenrollment from the health plan, or June 30, 2010. Bleeding events were classified as major, serious nonmajor, or minor. Health care costs for patients with major bleeding events were calculated.

Results

Among 48,260 patients with NVAF (mean age, 67 years), 34% had an incident bleeding event during a mean (SD) follow-up period of 802 (540) days. Incidence rates for bleeding events of any severity and major events were 29.6 and 10.4 per 100 patient-years, respectively. Bleeding incidence rates increased with greater CHADS₂ and HAS-BLED risk scores. All-cause health care costs for patients during a major bleeding event averaged $16,830. Average costs per patient with a major event increased from approximately $52 per day in the prebleeding period to approximately $63 per day in the postbleeding period. Costs for patients who did not experience a major bleeding event averaged approximately $38 per day.

Conclusions

Bleeding incidence among patients with NVAF in a real-world setting was high and increased with greater stroke and bleeding risk scores. Health care costs for patients with major bleeding events were elevated. All rights reserved.     

Efficacy and Safety of Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation Undergoing Elective Surgical Procedures: A Meta-analysis

Objective: The study objective was to determine if peri-operative bridging anticoagulation in patients with atrial fibrillation is beneficial or harmful.Design: Systematic review and meta-analysis.Setting: Inpatient or in-hospital setting.Participants: Adults with atrial fibrillation having a CHADS2 score >1 undergoing elective surgical procedure on anticoagulation.Methods: A systemic search of multiple databases (Cochrane, Medline, PubMed) was performed regarding studies conducted on efficacy and safety of perioperative bridging anticoagulation in patients with atrial fibrillation. Studies identified were reviewed by two authors individually before inclusion. The results were then pooled using Review Manager to determine the combined effect. Stroke/systemic embolism was considered as the primary efficacy outcome. Major bleeding was the primary safety outcome.Results: The systematic search revealed 108 potential articles. The full texts of 28 articles were retrieved for assessment of eligibility. After full text review, 25 articles were excluded. Three articles met inclusion criteria. No significant difference in stroke/systemic embolism with bridging anticoagulation was noted (risk ratio, 1.25-95% confidence interval [CI], 0.55–2.85). Bridging was associated with significantly higher risk of major bleeding (risk ratio, 3.29-95% CI, 2.25–4.81).Conclusion: An individualized approach is required when initiating peri-operative bridging anticoagulation. There is certainly a higher risk of bleeding with bridging anticoagulation and no difference in stroke/systemic embolism. However, the results cannot be extrapolated to patients who have valvular atrial fibrillation or CHADS2 score of 5 or greater.     

Cost-Utility Analysis of Oral Anticoagulants for Nonvalvular Atrial Fibrillation Patients at the Police General Hospital,Bangkok, Thailand

Purpose

The genetic polymorphism was one of the major considerations for adjusting doses of warfarin in Thai individuals. As a result, new oral anticoagulants (NOACs) were introduced to achieve therapeutic goals in stroke prevention in atrial fibrillation (SPAF) patients. However, a cost-utility analysis in a population-specific model was lacking in Thailand. This study was performed to determine which NOACs yielded population-specific, cost-effective results for SPAF compared with warfarin from both governmental and societal perspectives in Thailand.

Methods

A simplified Markov health state model was constructed to calculate the lifetime cost, life-years saved, and quality-adjusted life-years (QALYs) gained. Asia-specific clinical event parameters were defined from systematic searches of PubMed. Cost and utility input was obtained from hospital based data collection.

Findings

Although NOACs produced more life-years saved and QALYs gained resulting from the base-case versus warfarin, the lifetime costs of new alternatives increased to >1.4 times the comparative cost of warfarin. This caused an incremental cost-effective ratio that exceeded Thailand’s cost-effectiveness threshold. The probabilistic sensitivity analysis denoted the robustness of our model and revealed that dose-adjusted warfarin was the most cost-effective option in >99% of iterations. NOACs produced cost-effective results when the medication unit cost was decreased by at least 85%.

Implications

According to the results of this first cost-utility analysis in Thailand, warfarin is still the most cost-effective medication for SPAF from any perspective in Thailand at the threshold recommended by our health technology assessment guidelines.     

Persistence of Warfarin Therapy for Residents in Long-term Care Who Have Atrial Fibrillation

Background

Among long-term care (LTC) residents with atrial fibrillation (AF), the use of warfarin to prevent stroke has been shown to be suboptimal. For those who begin warfarin prophylaxis in LTC, persistence on this therapy has not been reported.

Objective

This study was conducted to estimate persistence on warfarin among LTC residents with AF.

Methods

A retrospective analysis was conducted by using data from an LTC database. Pharmacy dispensing data were used to track warfarin use in residents with a diagnosis of AF who were newly started on warfarin therapy. The main outcome measure was persistence of warfarin over the first year of therapy. Survival analysis included Kaplan-Meier plots and a multivariate Cox proportional hazards model to test the association of resident characteristics and conditions with warfarin discontinuation.

Results

A total of 148 residents new to warfarin therapy met all study inclusion criteria. Median age was 84 years; 69% were female. Median time to therapy discontinuation was 197 days (95% CI, 137–249) across all study residents. By 90 days after the initiation of therapy, 37% (95% CI, 28–47) of study residents had discontinued warfarin; by 1 year, 65% (54%–76%) had discontinued warfarin therapy. The multivariate Cox regression analysis found that the following factors were independently associated with discontinuation of warfarin therapy: age 65 to 74 years (hazard ratio [HR] = 3.01 [95% CI, 1.04–8.73]), female sex (HR = 0.45 [95% CI, 0.24–0.87]), Hispanic race/ethnicity (HR = 2.86 [95% CI, 1.30–6.26]), Midwest region (HR = 2.13 [95% CI, 1.02–4.48]), and Alzheimer disease or dementia (HR = 1.97 [95% CI, 1.05–3.68]).

Conclusions

Although clinical practice guidelines exist for the prevention of stroke in AF patients, persistence on warfarin therapy seems suboptimal in many LTC residents with AF.     

Perception of the Risk of Stroke and the Risks and Benefits of Oral Anticoagulation for Stroke Prevention in Patients With Atrial Fibrillation: A Cross-Sectional Study

ObjectiveTo assess the perception of the risk of stroke and the risks and benefits of oral anticoagulation (OAC) in patients with atrial fibrillation (AF).Patients and MethodsConsecutive patients with chronic AF who presented for an outpatient cardiology visit or were admitted to a noncritical care cardiology ward service from September 15 through December 20, 2017, were invited to participate in this survey. Participants were asked to estimate their stroke risk without OAC and bleeding risk with OAC using a quantitative risk scale. The reported values were compared with subjectively estimated risks derived from the CHA₂DS₂-VASc and HAS-BLED scores. Similarly, we compared patient perception of the stroke risk reduction afforded with OAC compared with what is reported in the literature.ResultsA total of 227 patients were included in the analysis. The mean ± SD CHA₂DS₂-VASc score was 4.3±1.6, and HAS-BLED score was 2.3±1.2. Atrial fibrillation was paroxysmal in 53.3% and persistent/permanent in 46.7%. There was a negligible correlation between patient perceived and estimated risk of stroke (r=0.07; P=.32), and bleeding (r=0.16; P=.02). Most patients overestimated their risks of stroke and bleeding: 120 patients (52.9%) perceived an annual stroke risk greater than 20%, and 115 (53.5%) perceived an annual bleeding risk with OAC greater than 10%. Most patients (n=204; 89.9%) perceived that OAC would reduce their annual stroke risk by at least 50%.ConclusionPerceived risks of stroke and bleeding are markedly overestimated in most patients with AF. Further research is needed to discern the root causes and to identify effective methods of bridging this alarming disparity.     

Radiofrequency Catheter Ablation and Modulation of Atrioventricular Conduction in Patients with Atrial Fibrillation

We attempted radiofrequency ablation of the AV junction with a sequential right- and left-sided approach in 78 patients affected by severely symptomatic, drug refractory atrial fibrillation. Stable third-degree A V block was obtained in 99% of cases and, after 3 months, persisted in 92% of cases. Single session, stepwise, radiofrequency modulation of the AV node was attempted in 13 patients with paroxysmal atrial fibrillation. During sinus rhythm, ablation of the slow and fast AV node pathways was performed in order to increase the nodal refractory period or to slow conduction. Clinically successful modulation of AV conduction was achieved in 15% of cases and persisted during a 3-month follow-up. In conclusion. AV junction ablation is a well-established means of treating atrial fibrillation, but implies the implant of a permanent pacemaker. AV node modulation avoids the pacemaker implant, but is efficacious only in a minority of patients. Thus, in patients affected by paroxysmal atrial fibrillation, AV modulation should be attempted first; if this is ineffective. AV ablation can be performed during the same session.     

rt-PA治疗急性脑梗死伴心房颤动的疗效观察

目的:探讨重组组织型纤溶酶原激活剂(rt-PA)治疗急性脑梗死伴房颤的疗效。方法:选取急性脑梗死伴房颤患者40例为观察组,另选取同期收治的急性脑梗死无房颤患者40例为对照组。2组均在发病4.5 h内使用rt-PA进行静脉溶栓治疗,观察治疗后继发性脑出血的发生率和死亡率,以及治疗后24 h、2周、1月的NIHSS评分和治疗1、3月后的m RS评分。结果:2组治疗后继发性脑出血的发生率和死亡率差异无统计学意义(均P0.05)。观察组治疗后24 h、2周、1月时NIHSS评分和治疗1月后的m RS评分高于对照组,差异有统计学意义(均P0.05)。结论:rt-PA能有效治疗发病4.5 h内的伴有房颤的急性脑梗死患者。     

Atrial fibrillation in patients with first-ever stroke: frequency, antithrombotic treatment before the event and effect on clinical outcome

BACKGROUND AND PURPOSES: Atrial fibrillation (AF) is an independent risk factor for stroke. The aims of this study were to assess: (i) the frequency of known or unknown AF in patients admitted to the hospital for a first-ever ischemic stroke and whether AF is associated with an adverse outcome at discharge (death or disability); (ii) the rates and determinants for the use of antithrombotic agents before stroke in patients with known AF and the adherence to the current treatment guidelines; and (iii) whether the lack of adherence to the current guidelines is associated with adverse outcome at discharge. METHODS: Consecutive patients with acute first-ever stroke admitted to an individual Stroke Unit between January 2000 to December 2003, were included in the study. Twelve-lead electrocardiogram (ECG) was performed in all patients on admission. Functional outcome was measured at discharge according to modified Rankin Score. RESULTS: A total of 1549 patients were included in the study: 238 patients (15.4%) were known to have AF and 76 (4.9%) were diagnosed with AF (unknown) on ECG performed on admission. At discharge 91 patients (5.9%) had died and 605 patients (39.0%) had died or were functionally dependent. Multivariate analysis showed that AF on admission was correlated with mortality or disability (OR = 1.58, 95% CI 1.09-2.30, P = 0.015). Before stroke, 124 out of 238 patients with known AF (52.1%) were not on antithrombotic therapy, 83 (34.9%) were receiving antiplatelet and 31 (13.0%) anticoagulant treatment. Previous transient ischemic attack, history of ischemic heart disease and hyperlipidemia were associated with the use of antithrombotic therapy. Only 24 out of 114 patients on antithrombotic treatment on admission were adequately treated according to the current guidelines. Of the adequately treated patients, 41.7% died or were disabled at discharge respect to 52.3% of the patients non-adequately treated (RR = 0.80, 95% CI 0.48-1.30). CONCLUSIONS: AF (on history or new diagnosis) was present in 20.3% of the patients with first-ever stroke admitted to a Stroke Unit and it was associated with increased mortality or disability. Only 10% of patients with known AF were previously receiving an adequate antithrombotic treatment according to current guidelines.