一项关于高强度华法林与传统抗血栓治疗预防抗磷脂综合征（WAPS）患者复发性血栓形成的随机临床试验。

A randomized clinical trial of high-intensity warfarin vs. conventional antithrombotic therapy for the prevention of recurrent thrombosis in patients with the antiphospholipid syndrome (WAPS).

作者信息

Finazzi G, Marchioli R, Brancaccio V, Schinco P, Wisloff F, Musial J, Baudo F, Berrettini M, Testa S, D'Angelo A, Tognoni G, Barbui T

机构信息

The Ospedali Riuniti, Bergamo, Italy.

出版信息

J Thromb Haemost. 2005 May;3(5):848-53. doi: 10.1111/j.1538-7836.2005.01340.x.

DOI:10.1111/j.1538-7836.2005.01340.x

PMID:15869575

Abstract

BACKGROUND

The optimal intensity of oral anticoagulation for the prevention of recurrent thrombosis in patients with antiphospholipid antibody syndrome is uncertain. Retrospective studies show that only high-intensity oral anticoagulation [target international normalized ratio (INR) >3.0] is effective but a recent randomized clinical trial comparing high (INR range 3.0-4.0) vs. moderate (INR 2.0-3.0) intensities of anticoagulation failed to confirm this assumption.

METHODS

We conducted a randomized trial in which 109 patients with antiphospholipid syndrome (APS) and previous thrombosis were given either high-intensity warfarin (INR range 3.0-4.5, 54 patients) or standard antithrombotic therapy (warfarin, INR range 2.0-3.0 in 52 patients or aspirin alone, 100 mg day(-1) in three patients) to determine whether intensive anticoagulation is superior to standard treatment in preventing symptomatic thromboembolism without increasing the bleeding risk.

RESULTS

The 109 patients enrolled in the trial were followed up for a median time of 3.6 years. Mean INR during follow-up was 3.2 (SD 0.6) in the high-intensity warfarin group and 2.5 (SD 0.3) (P < 0.0001) in the conventional treatment patients given warfarin. Recurrent thrombosis was observed in six of 54 patients (11.1%) assigned to receive high-intensity warfarin and in three of 55 patients (5.5%) assigned to receive conventional treatment [hazard ratio for the high intensity group, 1.97; 95% confidence interval (CI) 0.49-7.89]. Major and minor bleeding occurred in 15 patients (two major) (27.8%) assigned to receive high-intensity warfarin and eight (three major) (14.6%) assigned to receive conventional treatment (hazard ratio 2.18; 95% CI 0.92-5.15).

CONCLUSIONS

High-intensity warfarin was not superior to standard treatment in preventing recurrent thrombosis in patients with APS and was associated with an increased rate of minor hemorrhagic complications.

摘要

背景

抗磷脂抗体综合征患者预防复发性血栓形成的最佳口服抗凝强度尚不确定。回顾性研究表明，只有高强度口服抗凝治疗（目标国际标准化比值（INR）>3.0）有效，但最近一项比较高（INR范围3.0 - 4.0）与中等（INR 2.0 - 3.0）抗凝强度的随机临床试验未能证实这一假设。

方法

我们进行了一项随机试验，将109例患有抗磷脂综合征（APS）且既往有血栓形成的患者分为两组，一组给予高强度华法林治疗（INR范围3.0 - 4.5，共54例患者），另一组给予标准抗栓治疗（52例患者使用华法林，INR范围2.0 - 3.0，3例患者单独使用阿司匹林，每日100mg），以确定强化抗凝治疗在预防有症状血栓栓塞方面是否优于标准治疗，同时不增加出血风险。

结果

该试验纳入的109例患者中位随访时间为3.6年。高强度华法林组随访期间平均INR为3.2（标准差0.6），接受华法林常规治疗的患者平均INR为2.5（标准差0.3）（P < 0.0001）。在分配接受高强度华法林治疗的54例患者中有6例（11.1%）发生复发性血栓形成，在分配接受常规治疗的55例患者中有3例（5.5%）发生复发性血栓形成[高强度组的风险比为1.97；95%置信区间（CI）0.49 - 7.89]。接受高强度华法林治疗的15例患者（2例大出血）（27.8%）发生了大出血和小出血，接受常规治疗的8例患者（3例大出血）（14.6%）发生了大出血和小出血（风险比2.18；95% CI 0.92 - 5.15）。