Warfarin Management and Outcomes in Patients with Nonvalvular Atrial Fibrillation Within an Integrated Health Care System.
Warfarin Management and Outcomes in Patients with Nonvalvular Atrial Fibrillation Within an Integrated Health Care System.
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DOI：
10.18553/jmcp.2017.23.6.700
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发表时间：
2017-06-01
影响因子：
2.1
通讯作者：
Aranda, Gustavus Jr
中科院分区：
文献类型：
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作者：
An, JaeJin;Niu, Fang;Aranda, Gustavus Jr
背景：在临床实践中，华法林是治疗非瓣膜性心房颤动(NVAF)患者的常用治疗方法。了解当前药剂师领导的抗凝诊所管理模式和相关结果对于质量改进很重要；然而，目前几乎没有证据表明结果与管理模式相关。目的：(A)描述华法林管理模式，(B)评估综合医疗系统中NVAF患者华法林治疗与临床结果之间的关联。方法：采用Kaiser Permanente南加州数据，对2006年1月1日至2011年12月31日期间接受华法林治疗的NVAF患者进行了一项回顾性队列研究，跟踪研究至2013年12月31日。研究了与国际标准化比率(INR)监测、抗凝诊所药剂师干预(会诊)和华法林剂量调整相关的管理模式，以及年度流失率、治疗范围内时间(TTRs)和临床结果(中风或全身血栓和大出血)。结果：共有32,074名接受华法林治疗的NVAF患者被确定并随访了中位数3.8年。大约一半(49%)的患者是新开始华法林治疗。在华法林治疗6个月后，大约每3周进行一次INR监测和药剂师干预。63%的研究人群进行了≥-1华法林剂量调整，平均(SD)为6.7%(6.3)年剂量调整。华法林剂量调整发生在INR测量后的中位数1天(四分位数范围[IQR]1-3)。年流失率为3.3%~6.3%，中位数(IQR)为61%(46%~73%)。经常接受INR监测(每年≥27次)、药剂师干预(≥每年24次)或频繁调整华法林剂量(≥每年11次)的患者TTR值始终较低(最高四分位数的TTR值平均为45.3%-48.3%)。无论INR监测频率、药剂师干预或剂量调整次数如何，TTR越高，临床结果的风险越低。TTRs为65%的患者，即使经常接受药剂师干预，其中风或系统性血栓事件的发生率也与TTRs&65%或更少干预的患者相似(每100人年中风或系统性栓塞率分别为1.88和1.54，P=0.78)。与总有效率最高的四分位数(≥73%)相比，总有效率最低的四分位数(<；46%)与卒中或全身性栓塞的风险增加3倍(风险比[HR]=3.19，95%CI=2.71~3.77)，大出血的风险增加2倍(HR=2.10，95%CI=1.96~2.24)。结论：尽管及时调整华法林剂量进行密切监测，但仍有相当数量的具有挑战性的患者，尽管药师介入的次数较多，但总有效率仍处于次优水平。这些患者最终在抗凝诊所管理的NVAF患者中经历了更多的中风或系统性血栓和出血事件。对于不能达到最佳治疗范围的患者，需要新的个体化治疗或管理策略来改善结果。简介：本研究和论文由百时美施贵宝公司和辉瑞公司资助。来自百时美施贵宝公司和辉瑞公司的作者参与了这项研究的设计、数据的解释、手稿的审阅/修改，以及手稿最终版本的批准。AN获得了百时美施贵宝/辉瑞的研究资助。牛、拉希德和郑收到了百时美施贵宝/辉瑞向他们的机构发放的工资补偿。沃、辛格和阿兰达受雇于百时美施贵宝；布鲁诺在本研究期间受雇于百时美施贵宝。Mendes和Dills受雇于辉瑞，在本研究期间，Mendes是辉瑞心血管和代谢领域医疗团队的成员。Lang、Jazdzewski和Le没有已知的利益冲突要报告。研究概念和设计主要由An和Rashid以及其他作者贡献。牛与郑一起带头收集数据，安与门德斯和迪尔斯一起在其他作者的协助下进行数据解释。手稿由An撰写，并由门德斯、迪尔斯、沃、辛格、布鲁诺和阿兰达以及朗、勒和Jazdezewski修订。这项研究的部分发现于2015年10月28日在加拿大蒙特利尔举行的ROST 2015年会上公布。
BACKGROUND: Warfarin is a common treatment option to manage patients with nonvalvular atrial fibrillation (NVAF) in clinical practice. Understanding current pharmacist-led anticoagulation clinic management patterns and associated outcomes is important for quality improvement; however, currently little evidence associating outcomes with management patterns exists.OBJECTIVES: To (a) describe warfarin management patterns and (b) evaluate associations between warfarin treatment and clinical outcomes for patients with NVAF in an integrated health care system.METHODS: A retrospective cohort study was conducted among NVAF patients with warfarin therapy between January 1, 2006, and December 31, 2011, using Kaiser Permanente Southern California data, and followed until December 31, 2013. Management patterns related to international normalized ratio (INR) monitoring, anticoagulation clinic pharmacist intervention (consultation), and warfarin dose adjustments were investigated along with yearly attrition rates, time-in-therapeutic ranges (TTRs), and clinical outcomes (stroke or systemic embolism and major bleeding). Descriptive statistics and multivariable Cox proportional hazard models were used to determine associations between TTR and clinical outcomes.RESULTS: A total of 32,074 NVAF patients on warfarin treatment were identified and followed for a median of 3.8 years. About half (49%) of the patients were newly initiating warfarin therapy. INR monitoring and pharmacist interventions were conducted roughly every 3 weeks after 6 months of warfarin treatment. Sixty-three percent of the study population had ≥ 1 warfarin dose adjustments with a mean (SD) of 6.7 (6.3) annual dose adjustments. Warfarin dose adjustments occurred at a median of 1 day (interquartile ranges [IQR] 1-3) after the INR measurement. Yearly attrition rate was from 3.3% to 6.3% during the follow-up, and median (IQR) TTR was 61% (46%-73%). Patients who received frequent INR monitoring (≥ 27 times per year), pharmacist interventions (≥ 24 times per year), or frequently adjusted warfarin dose (≥ 11 times per year) consistently showed poor TTRs (mean TTR for the highest quartiles was 45.3%-48.3%). A higher TTR was associated with a lower risk of clinical outcomes regardless of frequency of INR monitoring, pharmacist interventions, or number of dose adjustments. Patients whose TTRs were < 65%, even with frequent pharmacist interventions, had similar stroke or systemic embolism event rates, as compared with patients with TTRs < 65% and less frequent interventions (1.88 vs. 1.54 stroke or systemic embolism rates per 100 person-years, respectively, P = 0.78). The lowest TTR quartile (< 46%) was associated with a 3 times higher risk of stroke or systemic embolism (hazard ratio [HR] = 3.19, 95% CI = 2.71-3.77) and a 2 times higher risk of major bleeding (HR = 2.10, 95% CI = 1.96-2.24) compared with the highest TTR quartile (≥ 73%).CONCLUSIONS: Despite close monitoring with timely warfarin dose adjustments, there were still a substantial number of challenging patients whose TTRs were suboptimal despite a higher number of pharmacist interventions. These patients eventually experienced more stroke or systemic embolism and bleeding events among NVAF patients managed by anticoagulation clinics. New individualized treatment or management strategies for patients who are not able to reach optimal therapeutic ranges are necessary to improve outcomes.DISCLOSURES: This research and manuscript were funded by Bristol-Myers Squibb Company and Pfizer. Authors from Bristol-Myers Squibb Company and Pfizer participated in the design of the study, interpretation of the data, review/revision of the manuscript, and approval of the final version of the manuscript. An received a grant for research support from Bristol-Myers Squibb/Pfizer. Niu, Rashid, and Zheng received a grant from Bristol-Myers Squibb/Pfizer to their institutions for salary reimbursement. Vo, Singh, and Aranda are employed by Bristol-Myers Squibb; Bruno was employed by Bristol-Myers Squibb at the time of this study. Mendes and Dills are employed by Pfizer, and Mendes was a member of the Pfizer Cardiovascular and Metabolic Field Medical Team during the time of this study. Lang, Jazdzewski, and Le have no known conflicts of interest to report. Study concept and design were contributed primarily by An and Rashid, along with the other authors. Niu took the lead in data collection, along with Zheng, and data interpretation was performed by An, along with Mendes and Dills, with assistance from the other authors. The manuscript was written by An and revised by Mendes, Dills, Vo, Singh, Bruno, and Aranda, along with Lang, Le, and Jazdezewski. Part of this study's findings was presented at the CHEST 2015 Annual Meeting in Montreal, Canada, on October 28, 2015.