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.     

Warfarin time in therapeutic range and its impact on healthcare resource utilization and costs among patients with nonvalvular atrial fibrillation

Background:

Warfarin is efficacious for reducing stroke risk among patients with nonvalvular atrial fibrillation (NVAF). However, the efficacy and safety of warfarin are influenced by its time in therapeutic range (TTR).

Objective:

To assess differences in healthcare resource utilization and costs among NVAF patients with low (<60%) and high (≥60%) warfarin TTRs in an integrated delivery network (IDN) setting.

Methods:

Patients with NVAF were identified from an electronic medical record database. Patients were required to have ≥6 international normalized prothrombin time ratio (INR) tests. NVAF patients were grouped into two cohorts: those with warfarin TTR <60% (low TTR) and those with warfarin TTR ≥60% (high TTR). Healthcare resource utilization and costs were evaluated during a 12 month follow-up period. Multivariable regressions were used to assess the impact of different warfarin TTRs on healthcare costs.

Results:

Among the study population, greater than half (54%, n?=?1595) had a low TTR, and 46% (n?=?1356) had a high TTR. Total all-cause healthcare resource utilization was higher among patients in the low TTR cohort vs. the high TTR cohort (number of encounters: 70.2 vs. 56.1, p?<?0.001). After adjusting for patient characteristics, total all-cause healthcare costs and stroke-related healthcare costs were $2398 (p?<?0.001) and $687 (p?=?0.02) higher, respectively, for patients in the low TTR cohort vs. the high TTR cohort.

Limitations:

In this retrospective study, we were only able to evaluate the association and not the causality between healthcare resource utilization and costs with the different warfarin TTRs.

Conclusion:

Many warfarin-treated NVAF patients have a low warfarin TTR. NVAF patients with low vs. patients with high warfarin TTR used healthcare resources to a greater extent, which was reflected in higher healthcare costs.     

Direct costs of warfarin treatment among patients with atrial fibrillation in a Finnish health care setting

ABSTRACT

Objective: The main objective was to estimate the mean direct costs of warfarin treatment for atrial fibrillation (AF) patients. Secondly, the costs of initiating warfarin treatment during a 60-day period and the impact of International Normalized Ratio (INR) and co-morbidities on costs were estimated.

Design and data: The study was performed as a retrospective cohort study over a 12‐month period in a Finnish communal health care setting. All AF patients aged 65 years or older (n = 250) with warfarin treatment were identified from the database of the health service district of an urban area. Patient specific information related to co-morbidities, INR-control, complications and health care resource use were collected. Cost information was obtained from the Finnish national health care unit cost list.

Methods: The effect of treatment balance and other background variables on treatment costs were evaluated using ordinary least squares regression (OLS), log-transformed OLS and generalized linear model (GLM). The mean costs were calculated on the basis of the different models and bias corrected and accelerated (BCa) bootstrap confidence intervals (CIs) were calculated for the mean costs.

Results: The best fitting cost model was log-transformed OLS. The costs of warfarin treatment on the basis of the log-transformed model were 589.82 euros (BCa 95% CI: 586.68–591.99) per patient compared to 616.00 euros (BCa 95% CI: 579.98–652.96) obtained with the OLS-model. For the treatment initiation period, the mean costs were 263 euros (BCa 95% CI: 218.90–314.71). Depending on the way that INR-control was defined, the mean costs were 95.27 euros or 166.92 euros higher for patients who were not in the defined INR-balance.

Conclusions: The INR-control has a significant impact on the warfarin treatment costs. The choice of model influences the estimated mean costs. In addition, different models identify statistically significant effects between different background variables and costs.     

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.     

达比加群酯预防心房颤动患者发生卒中的疗效和安全性分析

目的探讨达比加群酯预防心房颤动患者发生卒中的疗效和安全性。方法选取我院2015年1-12月收治的心房颤动患者200例,随机分为试验组和对照组,每组100例。对照组患者采用华法林治疗,试验组患者使用达比加群酯治疗。比较分析两组患者治疗后全身性栓塞、卒中、大出血的发生率。结果试验组卒中发生率为7.00%,对照组为16.00%,两组比较差异有统计学意义(χ~2=3.98,P<0.05);试验组全身性栓塞发生率为5.00%,对照组为14%,两组比较差异有统计学意义(χ~2=4.71,P<0.05);试验组大出血发生率为9.00%,对照组为19%,两组比较差异有统计学意义(χ~2=4.15,P<0.05)。结论在预防心房颤动患者发生卒中的疗效和安全性上,达比加群酯的效果较传统药物华法林显著。     

Comparing the economic burden of ischemic stroke patients with and without atrial fibrillation: a retrospective study in Beijing,China

Background: Little is known about the economic burden for ischemic stroke (IS) patients with atrial fibrillation (AF) in China.

Aim: We aimed to compare the economic burden of treatment-related costs in IS patients with AF vs. without AF in China.

Methods: This retrospective analysis used economic burden data from the Beijing urban health insurance database. Using a random sampling method, 10% of the patients diagnosed with IS from 1 January through 31 December 2012 were enrolled. First hospitalization was considered as the index event and hospital utilization after the index event was followed up until September 2013. Overall healthcare cost during the study period was analyzed.

Results: In 4061 patients with IS (mean?±?SD age, 68.45?±?13.95 years; AF: 992; without AF: 3069), the AF group had a higher percentage of patients with co-morbidities at baseline. Compared with the non-AF group, the AF group had significantly greater hospitalization at the index event (p?p?Conclusions: AF increased the use of healthcare resources, treatment cost, and economic burden in patients with IS. Therefore, prevention of cardio-embolic events in patients with AF by anticoagulants may decrease the economic burden in patients with IS.     

房颤合并肺部感染患者治疗过程出现不良反应一例

1例78岁房颤合并肺部感染患者,在其治疗过程中出现咯血,通过对患者相关治疗药物的分析,推测其咯血原因系华法林可能与胺碘酮、伏立康唑发生药物相互作用所致,并对相关文献证据进行了探讨。     

Impact of renal function on ischemic stroke and major bleeding rates in nonvalvular atrial fibrillation patients treated with warfarin or rivaroxaban: a retrospective cohort study using real-world evidence

Objectives: Renal dysfunction is associated with increased risk of cardiovascular disease and is an independent predictor of stroke and systemic embolism. Nonvalvular atrial fibrillation (NVAF) patients with renal dysfunction may face a particularly high risk of thromboembolism and bleeding. The current retrospective cohort study was designed to assess the impact of renal function on ischemic stroke and major bleeding rates in NVAF patients in the real-world setting (outside a clinical trial).

Methods: Medical claims and Electronic Health Records were retrieved retrospectively from Optum’s Integrated Claims–Clinical de-identified dataset from May 2011 to August 2014. Patients with NVAF treated with warfarin (2468) or rivaroxaban (1290) were selected. Each treatment cohort was stratified by baseline estimated creatinine clearance (eCrCl) levels. Confounding adjustments were made using inverse probability of treatment weights (IPTWs). Incidence rates and hazard ratios of ischemic stroke and major bleeding events were calculated for both cohorts.

Results: Overall, patients treated with rivaroxaban had an ischemic stroke incidence rate of 1.9 per 100 person-years (PY) while patients treated with warfarin had a rate of 4.2 per 100 PY (HR?=?0.41 [0.21–0.80], p?=?.009). Rivaroxaban patients with an eCrCl below 50?mL/min (N?=?229) had an ischemic stroke rate of 0.8 per 100 PY, while the rate for the warfarin cohort (N?=?647) was 6.0 per 100 PY (HR?=?0.09 [0.01–0.72], p?=?.02). For the other renal function levels (i.e. eCrCl 50–80 and ≥80?mL/min) HRs indicated no statistically significant differences in ischemic stroke risks. Bleeding events did not differ significantly between cohorts stratified by renal function.

Conclusions: Ischemic stroke rates were significantly lower in the overall NVAF population for rivaroxaban vs. warfarin users, including patients with eCrCl below 50?mL/min. For all renal function groups, major bleeding risks were not statistically different between treatment groups.     

阿司匹林联合华法林对冠心病合并心房纤颤患者的安全性和有效性分析

目的观察阿司匹林联合华法林对冠心病合并心房纤颤的有效性和安全性。方法回顾性分析2012年8月至2013年8月46例来我科住院治疗的冠心病合并心房纤颤患者,分为观察组(阿司匹林和华法林联合治疗)和对照组(华法林单药治疗),每组23例。随访1年,比较两组血栓栓塞发生率、出血发生率及患者的肾功能。结果观察组患者血栓栓塞发生率、出血发生率及肾功能各项指标与对照组比较,差异无统计学意义(P>0.05)。结论阿司匹林联合华法林治疗冠心病合并房颤的脑血栓发生率较低,出血风险较小,对肾功能也没有严重损害,但与华法林单药治疗比较,差异无统计学意义。     

心房颤动患者近期缺血性卒中后应用依多沙班抗凝治疗的时机和剂量的研究进展

心房颤动（Atrial fibrillation,AF）是成人中常见的持续性心律失常,给医疗保健增加巨大负担。心律失常不仅与生活质量下降和频繁住院有关,而且与缺血性卒中、其他血栓栓塞事件和死亡率增加的风险增加有关。AF患者的缺血性卒中风险因个体风险状况而异,不使用口服抗凝剂（Oral anticoagulant,OAC）的缺血性卒中发生率约为3.20/100人年。与其他卒中病因相比,AF相关卒中患者的预后更差。所有AF患者都必须实施个体卒中风险评估和使用最佳卒中预防策略。依多沙班的适应证是预防AF患者的卒中,该药口服给药,剂量为60 mg,每日1次。本文讨论了AF患者近期缺血性卒中后应用依多沙班抗凝治疗的时机和剂量的研究进展。     

心房颤动并发脑栓塞的严重程度与纤维蛋白原的相关性

目的探讨心房颤动并发脑栓塞患者严重程度与血浆纤维蛋白原(Fib)的相关性。方法收集住院治疗的合并心房颤动的脑栓塞患者80例,于入院时查血浆Fib,并行美国国立卫生研究院卒中量表(NIHSS)评分,分析两者之间的相关性。定义NIHSS评分≥15分为重症脑栓塞,Logistic回归分析其与Fib的危险相关度。入组患者经牛津郡社区卒中计划(OCSP)分型后,以腔隙性梗死作为参照,Logistic回归分析其他亚型Fib的水平相对危险度。结果脑栓塞患者Fib与NIHSS评分具有显著相关性(r=0.264,P<0.05)。重症脑栓塞与Fib的单因素回归分析显示OR(95%CI)为2.404(1.107-5.222),经性别、年龄、高血压、糖尿病多因素校正后为3.292(1.322-8.200)(P<0.05)。完全前循环梗死组Fib水平是腔隙性梗死组的3.166倍(95%CI为1.259-7.961,P<0.05)。结论血浆Fib水平可一定程度的反映房颤并发脑栓塞患者的病情严重程度。     

华法林用于各卒中风险非瓣膜性房颤患者对其血栓栓塞与出血风险的影响

目的分析非瓣膜性房颤住院患者使用华法林进行抗凝治疗和国际标准化比值(INR)监测状况,以期更好地指导临床抗凝治疗,减少抗凝治疗中血栓栓塞和出血事件发生。方法收集2017年6-12月汕头大学医学院第一附属医院住院治疗的非瓣膜性房颤患者的临床资料、用药情况,监测患者住院期间INR值。采用CHA2DS2-VASc评分对所有患者进行卒中风险评估。随访2年,观察患者因血栓栓塞事件、出血事件再入院情况。结果本研究共纳入病例662例,其中144例使用华法林。在CHA2DS2-VASc评分分层中,中、高危卒中风险患者服用华法林组的INR处于1.5~2.5区间的比例高于无服用组(P<0.05)。在140例服用华法林且INR数据完整患者中,63例(45.0%)INR处于1.0~1.5区间,仅29例(20.7%)INR处于2.0~3.0区间;高危卒中风险患者INR在1.5~2.0组发生血栓栓塞、出血事件再次住院的比例低于INR非1.5~2.0组(P<0.05)。结论临床上华法林使用率低,抗凝强度低。对于中、高危卒中风险患者来说,正确服用华法林有助于将INR控制在1.5~2.5区间。当高危卒中患者的INR处于1.5~2.0区间时可减少血栓栓塞、出血风险的发生。     

Knowledge of stroke and medication adherence among patients with recurrent stroke or transient ischemic attack in Indonesia: a multi-center,cross-sectional study

International Journal of Clinical Pharmacy - BackgroundThere is a limited data in Indonesia regarding the stroke knowledge and medication adherence among stroke survivors.ObjectiveTo assess the...     

某院托管前后心房纤颤治疗情况比较研究

目的了解蒲江县人民医院被托管1年来心房纤颤（房颤）患者的治疗情况,探讨医院托管模式对房颤治疗的影响。方法采用回顾性研究方法,分析托管后2011年4月至2012年8月在该院内科住院、资料相对完整的房颤患者的临床资料．并以被拖管前2010年1月至20112年3月住院患者作为对照。结果被托管后1年来,初发房颤、阵发性房颤的复律无明显差异,行射频消融的比例提高,使用血管紧张素转换酶抑制剂（ACEI）或血管紧张素Ⅱ受体拮抗剂（ARB）的比例提高。持续性房颤抗栓治疗的比较提高,使用华法林和低分子肝素的比例提高。永久性房颤服用华法林的比较有所提高,心室率控制的比例提高。结论托管后1年来,该院房颤的治疗情况更加规范,但房颤的抗栓治疗仍需要加强．     

心房颤动采用三联疗法和双重抗血小板疗法抗血栓治疗策略对卒中、主要不良心脑血管事件、出血事件、全因病死率影响的Meta分析

目的 综合评价三联疗法(TT)和双重抗血小板治疗(DAPT)的策略在心房颤动(AF)病人接受经皮冠状动脉介入治疗(PCI)后对卒中、主要不良心脑血管事件(MCAE)、出血事件、全因病死率的影响.方法 检索PubMed,Embase,Web of Science数据库中2000―2018年的文章.根据纳入和排除标准进行筛...