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直接口服抗凝剂与华法林对老年房颤合并缺血性卒中患者的临床疗效:以患者为中心的卒中患者偏好结局与疗效研究(PROSPER)的结果

Clinical Effectiveness of Direct Oral Anticoagulants vs Warfarin in Older Patients With Atrial Fibrillation and Ischemic Stroke: Findings From the Patient-Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) Study.

作者信息

Xian Ying, Xu Haolin, O'Brien Emily C, Shah Shreyansh, Thomas Laine, Pencina Michael J, Fonarow Gregg C, Olson DaiWai M, Schwamm Lee H, Bhatt Deepak L, Smith Eric E, Hannah Deidre, Maisch Lesley, Lytle Barbara L, Peterson Eric D, Hernandez Adrian F

机构信息

Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.

Department of Neurology, Duke University Medical Center, Durham, North Carolina.

出版信息

JAMA Neurol. 2019 Oct 1;76(10):1192-1202. doi: 10.1001/jamaneurol.2019.2099.

Abstract

IMPORTANCE

Current guidelines recommend direct oral anticoagulants (DOACs) over warfarin for stroke prevention in patients with atrial fibrillation (AF) who are at high risk. Despite demonstrated efficacy in clinical trials, real-world data of DOACs vs warfarin for secondary prevention in patients with ischemic stroke are largely based on administrative claims or have not focused on patient-centered outcomes.

OBJECTIVE

To examine the clinical effectiveness of DOACs (dabigatran, rivaroxaban, or apixaban) vs warfarin after ischemic stroke in patients with AF.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included patients who were 65 years or older, had AF, were anticoagulation naive, and were discharged from 1041 Get With The Guidelines-Stroke-associated hospitals for acute ischemic stroke between October 2011 and December 2014. Data were linked to Medicare claims for long-term outcomes (up to December 2015). Analyses were completed in July 2018.

EXPOSURES

DOACs vs warfarin prescription at discharge.

MAIN OUTCOMES AND MEASURES

The primary outcomes were home time, a patient-centered measure defined as the total number of days free from death and institutional care after discharge, and major adverse cardiovascular events. A propensity score-overlap weighting method was used to account for differences in observed characteristics between groups.

RESULTS

Of 11 662 survivors of acute ischemic stroke (median [interquartile range] age, 80 [74-86] years), 4041 (34.7%) were discharged with DOACs and 7621 with warfarin. Except for National Institutes of Health Stroke Scale scores (median [interquartile range], 4 [1-9] vs 5 [2-11]), baseline characteristics were similar between groups. Patients discharged with DOACs (vs warfarin) had more days at home (mean [SD], 287.2 [114.7] vs 263.0 [127.3] days; adjusted difference, 15.6 [99% CI, 9.0-22.1] days) during the first year postdischarge and were less likely to experience major adverse cardiovascular events (adjusted hazard ratio [aHR], 0.89 [99% CI, 0.83-0.96]). Also, in patients receiving DOACs, there were fewer deaths (aHR, 0.88 [95% CI, 0.82-0.95]; P < .001), all-cause readmissions (aHR, 0.93 [95% CI, 0.88-0.97]; P = .003), cardiovascular readmissions (aHR, 0.92 [95% CI, 0.86-0.99]; P = .02), hemorrhagic strokes (aHR, 0.69 [95% CI, 0.50-0.95]; P = .02), and hospitalizations with bleeding (aHR, 0.89 [95% CI, 0.81-0.97]; P = .009) but a higher risk of gastrointestinal bleeding (aHR, 1.14 [95% CI, 1.01-1.30]; P = .03).

CONCLUSIONS AND RELEVANCE

In patients with acute ischemic stroke and AF, DOAC use at discharge was associated with better long-term outcomes relative to warfarin.

摘要

重要性

当前指南推荐,对于高危心房颤动(AF)患者,在预防卒中方面直接口服抗凝剂(DOACs)优于华法林。尽管在临床试验中已证明DOACs有效,但关于DOACs与华法林用于缺血性卒中患者二级预防的真实世界数据主要基于行政索赔,或未关注以患者为中心的结局。

目的

研究AF患者缺血性卒中后使用DOACs(达比加群、利伐沙班或阿哌沙班)与华法林相比的临床疗效。

设计、地点和参与者:这项队列研究纳入了年龄在65岁及以上、患有AF、未接受过抗凝治疗且于2011年10月至2014年12月期间从1041家参与“遵循卒中指南”项目的医院因急性缺血性卒中出院的患者。数据与医疗保险索赔相关联以获取长期结局(截至2015年12月)。分析于2018年7月完成。

暴露因素

出院时使用DOACs与华法林的处方情况。

主要结局和测量指标

主要结局为居家时间,这是以患者为中心的指标,定义为出院后无死亡和机构护理的总天数,以及主要不良心血管事件。采用倾向得分重叠加权法来解释组间观察到的特征差异。

结果

在11662例急性缺血性卒中幸存者中(年龄中位数[四分位间距]为80[74 - 86]岁),4041例(34.7%)出院时使用DOACs,7621例使用华法林。除国立卫生研究院卒中量表评分(中位数[四分位间距],4[1 - 9]对5[2 - 11])外,两组间基线特征相似。出院时使用DOACs(与华法林相比)的患者在出院后第一年有更多的居家天数(均值[标准差],287.2[114.7]天对263.0[127.3]天;调整后差异,15.6[99%置信区间,9.0 - 22.1]天),且发生主要不良心血管事件的可能性较小(调整后风险比[aHR],0.89[99%置信区间,0.83 - 0.96])。此外,在使用DOACs的患者中,死亡(aHR,0.88[95%置信区间,0.82 - 0.95];P <.001)、全因再入院(aHR,0.93[95%置信区间,0.88 - 0.97];P = 0.003)、心血管再入院(aHR,0.92[95%置信区间,0.86 - 0.99];P = 0.02)、出血性卒中(aHR,0.69[95%置信区间,0.50 - 0.95];P = 0.02)以及因出血住院(aHR,0.89[95%置信区间,0.81 - 0.97];P = 0.009)的情况较少,但胃肠道出血风险较高(aHR,1.14[95%置信区间,1.01 - 1.30];P = 0.03)。

结论和相关性

在急性缺血性卒中和AF患者中,出院时使用DOACs相对于华法林与更好的长期结局相关。

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