阿司匹林预防复发性静脉血栓栓塞症：INSPIRE 协作组。

Aspirin for the prevention of recurrent venous thromboembolism: the INSPIRE collaboration.

机构信息

From the National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia (J.S., A.C.K., R.M.); the Division of Internal and Cardiovascular Medicine and Stroke Unit, Department of Internal Medicine, University of Perugia, Perugia, Italy (C.B., G.A.); the Population Health Research Institute, McMaster University, Hamilton, ON, Canada (J.W.E.); the Department of Cardiothoracic and Vascular Sciences, University of Padua, Padua (P.P.); and the Department of Haematology, South Eastern Area Laboratory Services (SEALS), Prince of Wales Hospital, Sydney, Australia (T.A.B.).

出版信息

Circulation. 2014 Sep 23;130(13):1062-71. doi: 10.1161/CIRCULATIONAHA.114.008828. Epub 2014 Aug 25.

DOI:10.1161/CIRCULATIONAHA.114.008828

PMID:25156992

Abstract

BACKGROUND

In patients with a first unprovoked venous thromboembolism (VTE) the risk of recurrent VTE remains high after anticoagulant treatment is discontinued. The Aspirin for the Prevention of Recurrent Venous Thromboembolism (the Warfarin and Aspirin [WARFASA]) and the Aspirin to Prevent Recurrent Venous Thromboembolism (ASPIRE) trials showed that aspirin reduces this risk, but they were not individually powered to detect treatment effects for particular outcomes or subgroups.

METHODS AND RESULTS

An individual patient data analysis of these trials was planned, before their results were known, to assess the effect of aspirin versus placebo on recurrent VTE, major vascular events (recurrent VTE, myocardial infarction, stroke, and cardiovascular disease death) and bleeding, overall and within predefined subgroups. The primary analysis, for VTE, was by intention to treat using time-to-event data. Of 1224 patients, 193 had recurrent VTE over 30.4 months' median follow-up. Aspirin reduced recurrent VTE (7.5%/yr versus 5.1%/yr; hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.51-0.90; P=0.008), including both deep-vein thrombosis (HR, 0.66; 95% CI, 0.47-0.92; P=0.01) and pulmonary embolism (HR, 0.66; 95% CI, 0.41-1.06; P=0.08). Aspirin reduced major vascular events (8.7%/yr versus 5.7%/yr; HR, 0.66; 95% CI, 0.50-0.86; P=0.002). The major bleeding rate was low (0.4%/yr for placebo and 0.5%/yr for aspirin). After adjustment for treatment adherence, recurrent VTE was reduced by 42% (HR, 0.58; 95% CI, 0.40-0.85; P=0.005). Prespecified subgroup analyses indicate similar relative, but larger absolute, risk reductions in men and older patients.

CONCLUSIONS

Aspirin after anticoagulant treatment reduces the overall risk of recurrence by more than a third in a broad cross-section of patients with a first unprovoked VTE, without significantly increasing the risk of bleeding.

CLINICAL TRIAL REGISTRATION URL

www.anzctr.org.au. Unique identifier: ACTRN12611000684921.

摘要

背景

在首次无诱因静脉血栓栓塞症（VTE）患者中，抗凝治疗停止后，VTE 复发的风险仍然很高。阿司匹林预防静脉血栓栓塞复发（Warfarin 和阿司匹林[WARFASA]）和阿司匹林预防静脉血栓栓塞复发（ASPIRE）试验表明，阿司匹林可降低这种风险，但它们各自的研究均未显示出针对特定结局或亚组的治疗效果。

方法和结果

在这些试验结果公布之前，计划进行一项针对这些试验的个体患者数据分析，以评估阿司匹林与安慰剂在 VTE、主要血管事件（VTE 复发、心肌梗死、卒中和心血管疾病死亡）和出血方面的疗效，总体和预先设定的亚组。VTE 的主要分析是通过使用时间事件数据的意向治疗进行的。在 1224 名患者中，有 193 名患者在中位随访 30.4 个月时出现 VTE 复发。阿司匹林降低了 VTE 复发率（7.5%/年比 5.1%/年；风险比[HR]，0.68；95%置信区间[CI]，0.51-0.90；P=0.008），包括深静脉血栓形成（HR，0.66；95%CI，0.47-0.92；P=0.01）和肺栓塞（HR，0.66；95%CI，0.41-1.06；P=0.08）。阿司匹林降低了主要血管事件的发生率（8.7%/年比 5.7%/年；HR，0.66；95%CI，0.50-0.86；P=0.002）。大出血发生率较低（安慰剂为 0.4%/年，阿司匹林为 0.5%/年）。经过治疗依从性调整后，VTE 复发风险降低了 42%（HR，0.58；95%CI，0.40-0.85；P=0.005）。预先设定的亚组分析表明，男性和老年患者的相对风险降低相似，但绝对风险降低更大。