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.     

Mixed Treatment Comparison Meta-Analysis of Aspirin,Warfarin, and New Anticoagulants for Stroke Prevention in Patients With Nonvalvular Atrial Fibrillation

Background

Warfarin and aspirin are used to prevent stroke in patients with atrial fibrillation (AF). There are inherent challenges with both treatments, including variable and inconsistent benefit and increased bleeding risks. The availability of new anticoagulants offers some alternatives.

Objective

A mixed treatment comparison meta-analysis to evaluate direct and indirect treatment data including aspirin, warfarin apixaban, dabigatran, edoxaban, and rivaroxaban for the prevention of primary or secondary stroke in patients with AF.

Methods

A comprehensive, systematic literature search was conducted to identify randomized trials comparing aspirin, warfarin, apixaban, dabigatran, edoxaban, and rivaroxaban in patients with AF requiring treatment for stroke prevention. Open-label and blinded designs were included if they evaluated any stroke or any bleeding event. Data on stroke and bleeding events were abstracted, verified, evaluated, scored, and entered into Aggregate Data Drug Information System version 1.16 to generate a mixed treatment comparison meta-analysis. Direct and indirect comparisons were evaluated, and we looked for inconsistency in closed loop structures. Data are reported as rate ratios with 95% credible intervals. In addition, we reviewed variance statistics and explored variance with node-splitting models.

Results

Our literature search yielded 30 articles, 21 of which were included. All treatments except aspirin reduced the risk of any stroke compared with placebo. Warfarin (0.43 [0.33–0.57]), apixaban (0.37 [0.27–0.54]), dabigatran (0.34 [0.21–0.57]), rivaroxaban (0.36 [0.22–0.60]), and aspirin with clopidogrel (0.73 [0.53–0.99]) were more protective than aspirin alone. Warfarin and the new anticoagulants were similar in the reduction of stroke, vascular death, and mortality. There was no difference in major bleeding between any treatment group. There were more nonmajor bleeding events when comparing warfarin and apixaban (1.83 [1.05–4.03]); no other differences between warfarin and the other new anticoagulants were found.

Conclusions

This mixed treatment comparison meta-analysis found similarity between warfarin and the new anticoagulants with the exception of one comparison, in which warfarin was associated with more non-major bleeding than apixaban. Thus, the new anticoagulants are therapeutically comparable when warfarin is inappropriate.     

Reviewing a Clinical Decision Aid for the Selection of Anticoagulation Treatment in Patients With Nonvalvular Atrial Fibrillation: Applications in a US Managed Care Health Plan Database

PurposeThe Clinical Decision Aid was created to assist in selecting anticoagulant therapies for patients with nonvalvular atrial fibrillation. The aid incorporates a patient’s absolute risk for stroke and bleeding, relative stroke risk reduction, and increase in relative bleeding risk to identify the agent with the lowest net risk. We describe theoretical implications of utilizing the aid at a US managed care population level.MethodsThis retrospective study used claims data from a large US managed care database including enrollees in commercial and Medicare Advantage plans. The distribution of patients across each possible combination of scores on the HAS-BLED scale (evidence of hypertension, abnormal renal or liver function, stroke, bleeding, labile INR, age >65 years, and drugs or alcohol abuse or dependence) and the CHA₂DS₂-VASc scale (CHADS₂ [congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism] with additional nonmajor stroke risk factors, including age 65–74 years, female sex, and vascular disease) was generated. We assessed the correlation between the HAS-BLED and CHA₂DS₂-VASc scores and derived the optimal treatment options based on various bleeding ratios.FindingsData from 48,260 patients were included in the analysis. The MAPD subset had a higher mean HAS-BLED score (2.17 vs 1.39; P < 0.001) and a higher mean CHA₂DS₂-VASc score (3.35 vs 2.05; P < 0.001) than did the commercial subset. Pearson coefficients suggested a moderate to strong positive correlation between the HAS-BLED and CHA₂DS₂-VASc scores among the commercial (0.730; P < 0.001) and MAPD (0.568; P < 0.001) enrollees. Based on a 2:1 bleeding-to-stroke risk ratio, 70.50% of patients would be recommended treatment with apixaban; 25.86%, no treatment; 3.62%, acetylsalicylic acid; and 0.01%, dabigatran 150 mg, if the Clinical Decision Aid were to be used for anticoagulant treatment selection.ImplicationsEvidence-based clinical decision–making tools utilizing risk assessment for recommending a treatment may be valuable for not only health care providers but also health care payers in optimizing care at the population level.     

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。     

Emergency Department Use by Adult Medicaid Patients after Implementation of Managed Care

OBJECTIVE: To determine whether the advent of a mandatory Medicaid managed care (MMC) plan had any effect on emergency department (ED) utilization by adult Medicaid patients at an urban teaching hospital. METHODS: This was a retrospective cohort study using four years of ED records encompassing the year prior to initiation of MMC (1994-95), the enrollment year (1995-96), and two years after the program had matured (1996-98). RESULTS: Total ED census declined slightly, then returned to 1995 levels. Emergency department use by MMC patients declined steadily, with the 1998 figure of 5,888 representing a 40% decline over the pre-MMC volume of 9,849. Visits by MMC patients with acute illness or injury declined by 29%; MMC low-acuity visits decreased by 43%. Medicaid managed care low-acuity after-hours/weekend visits declined by 19%, then leveled off. The MMC enrollment was stable throughout the study period. CONCLUSIONS: Mandatory managed care can be associated with considerable diminution in ED use by Medicaid patients. This decline is most pronounced in low-acuity triage categories, and least evident after hours and on weekends.     

Standardizing Communications Improves Use of Palliative Care in Patients With Stroke

Patients who have sustained a severe stroke have immediate palliative care needs, and poor communication is a gap in quality that increases length of stay (LOS) and costs, which decreases efficient resource utilization. To standardize communication between families and treatment teams in the intensive care unit (ICU) and demonstrate improvement in LOS and costs, a communication bundle was prospectively implemented in 22 patients and compared against a retrospective control arm of 22 patients. The intervention group demonstrated significant improvement in median ICU and hospital LOS and ICU costs. Standardizing communication significantly improved resource utilization in severe stroke patients.     

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.     

老年患者房颤并发脑卒中的临床特征及其预后

为探讨老年患者房颤并发脑卒中的临床特征和预后,将房颤并发首次脑卒中的２５例老年患者列为研究对象（ＡＦ组）,另选年龄、性别与ＡＦ组相匹配的脑血栓形成脑卒中患者２５例为对照组,分别于脑卒中发病〉４８ｈ和治疗１个后评估２组患者的神经功能缺损程度和日常生活活动功能（ＡＤＬ）。结果：入院时ＡＦ组的神经功能和ＡＤＬ与对照组比较差异有显著性（Ｐ〈０．０５和０．００１）;１个月的ＡＦ神经功能和ＡＤＬ的恢复程度仍明     

综合超声技术检测非瓣膜性房颤缺血性脑卒中栓子来源的研究

目的研究非瓣膜性心房颤动(房颤)患者缺血性脑卒中可能的栓子来源。方法非瓣膜性房颤患者140例,应用经食管超声心动图(TEE)和外周血管超声技术检测缺血性脑卒中的左房危险因素(左房和/或左心耳内有重度自发声学显影和血栓)、主动脉危险因素(升主动脉和主动脉弓粥样斑块)、颈动脉危险因素(颈动脉复合型粥样斑块)和卵圆孔未闭。结果140例患者中21例(15%)发生缺血性脑卒中。具有左房、主动脉和颈动脉危险因素者分别为61.4%(86/140)、8.6%(12/140)和20.0%(28/140),脑卒中发生率分别为20.9%(18/86)、16.7%(2/12)和39.3%(11/28),同时存在左房和颈动脉危险因素者占14.3%(20/140),脑卒中发生率为50.0%(10/20);无危险因素者占28.6(40/140),脑卒中发生率为2.5%(1/40)。存在危险因素患者脑卒中的发生率明显高于无危险因素者(P<0.05～0.001)。结论左房、主动脉、颈动脉危险因素是房颤患者缺血性脑卒中的主要栓子来源,同时存在多种危险因素,特别是同时存在左房和颈动脉危险因素的房颤患者为脑卒中的高危人群;TEE和外周血管超声为房颤患者栓塞的进一步危险分层提供了精确方法。     

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.     

An Endovascular Approach to Cardioembolic Stroke Prevention in Atrial Fibrillation Patients

This report is of a 62-year-old woman presenting with a 3-year history of chronic atrial fibrillation (AF) and unable to tolerate chronic warfarin therapy due to bleeding episodes and unstable INR values. Additional high risk factors for stroke are a history of congestive heart failure and previous embolic stroke. Percutaneous left atrial appendage transcatheter occlusion (PLAATO™) was performed to seal the LAA. A transesophageal echocardiography (TEE) at the 1- and 6-month follow-up showed no device migration and no new thrombus related to the implant. The patient has been doing well on postprocedure aspirin with no embolic events. (PACE 2003; 26[Pt. II]:1604–1606)     

Use of Care by Home-dwelling Stroke Patients during Three Years following Hospital Discharge

Of 82 stroke survivors who had been discharged from hospital, 49 were still living at home after a three-year period. Thirty-three of these patients formed the population of the present study of the use of care at home. Sixty-one percent had received professional care and 88% had received family care. Although their overall functional status indicated only mild handicaps, after three years patients still reported a large number of disabilities and problems. The average weekly amount of family care was 37 h, and many family carers experienced a high burden of care and had emotional problems coping with the patients' disabilities. Concerning factors related to the use of care, in spite of the relatively small number of study patients, some interesting hypotheses can be advanced.     

脑卒中患者姑息照护的研究进展

脑卒中是一种常见的致死、致残率极高的神经系统疾病。在我国,脑卒中是造成城乡居民死亡的首要原因。尽管随着现代诊疗水平的提高,病死率有所下降,但致残率仍很高,同时患者常伴有抑郁、焦虑等心理障碍。     

A Health Promotion Intervention for Families in a Medicaid Managed Care Plan

OBJECTIVE: To determine whether implementation of an intervention based on a model of health promotion will encourage patients to seek care from their primary care provider (PCP) and reduce visits to the pediatric ED (PED) for minor illness. METHODS: Prospective, randomized, controlled study in the PED of an urban children's hospital (CH). Children <13 months old, enrolled in a Medicaid managed care plan, who identified the CH as their site for primary care and presented to the PED for evaluation of minor illness were enrolled after being seen by the triage nurse, before being seen by a physician. Subjects were randomly assigned to the intervention (I) group or control (C) group. Parents of all enrollees completed a survey about health care utilization habits. Each family in the I group received health promotion teaching from a single investigator. The intervention consisted of a review of the child's medical record with the parents, an explanation of what to expect at future well-child visits, and a discussion of the role of the PCP. A follow-up appointment was also provided prior to discharge from the PED. The C group received usual care. Use of health care by all subjects was tracked for one year by medical record review and phone interviews at six and 12 months. RESULTS: 102 subjects in the I group and 93 in the C group (mean +/- SD ages 6.4 months +/- 3.8 and 7.2 months +/- 3.9, respectively, p = 0.15) were enrolled from March 1996 to November 1996. The two groups were similar with respect to demographics and overall health status at enrollment. At study entry: 94 of 102 (92%) subjects in I and 87 of 93 (94%) in C had made at least one visit to the PED in the previous 12 months (p = 0.11); 95 of 102 (93%) in I and 75 of 93 (81%) in C had seen their PCP at least once for well-child care (p = 0.24). Twelve-month follow-up by medical record review was completed for all subjects; phone interviews were completed in 90 of 102 (88%) in I and 80 of 93 (86%) in C. At 12-month follow-up: 84 of 102 (82%) in I and 73 of 93 (78%) in C had made at least one visit to the PED (p = 0.59); 81 of 102 (79%) in I and 77 of 93 (83%) in C had made at least one visit to their CH PCP (p = 0.54). CONCLUSIONS: There was no difference in health care utilization between the intervention and control groups at 12-month follow-up. The health promotion intervention did not alter utilization habits.     

老年房颤患者华法林抗凝治疗社区管理与专科管理的对比研究

目的：心房纤颤是老年最常见的心律失常之一,并且带来了如外周血管血栓形成、肺梗死、脑卒中等并发症。口服抗凝治疗是预防该类并发症的有效手段,但监测繁琐、有药物不良反应风险等。本实验为寻找有效的房颤管理模式,设计了社区管理模式,并与专科管理模式进行对照,以研究社区管理模式是否适合老年房颤患者的管理。方法：纳入在我院就诊的老年房颤患者107名,随机分入社区管理组及专科管理组,其中专科管理组患者在珠海市人民医院门诊常规就诊,而社区管理组在所属社区进行治疗。对照比较在抗凝达标率、华法林相关不良反应事件发生率（出血、血栓事件）、及费用方面的差异。结果：与专科管理组比较,社区管理组在抗凝达标率（分别为61.2%,64.2%,P〉0.05）、出血及血栓事件（P值分别为0.133,0.279）发生率方面无明显统计学差异,但是在总体费用方面存在着统计学差异（P〈0.001）。结论：老年房颤患者华法林抗凝治疗在社区管理有着与专科管理相似的可行性、安全性及有效性,并且有费用方面的优势。     

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.