血栓形成预防试验：华法林治疗的依从性及残留效应研究

Thrombosis prevention trial: compliance with warfarin treatment and investigation of a retained effect.

作者信息

Rudnicka Alicja R, Ashby Deborah, Brennan Patrick, Meade Tom

机构信息

Department of Environmental and Preventive Medicine, Medical Research Council Epidemiology and Medical Care Unit, Wolfson Institute of Preventive Medicine, London, England.

出版信息

Arch Intern Med. 2003 Jun 23;163(12):1454-60. doi: 10.1001/archinte.163.12.1454.

DOI:10.1001/archinte.163.12.1454

PMID:12824095

Abstract

BACKGROUND

The Thrombosis Prevention Trial was a primary prevention factorial trial that reported a reduction in the risk of coronary heart disease (CHD) with warfarin and/or aspirin. This article examines compliance (duration of treatment) with warfarin treatment and whether warfarin has a retained effect.

METHODS

Risk of CHD while complying with warfarin treatment was compared with risk of CHD in all participants randomized to placebo. Simultaneously, risk of CHD in ex-warfarin users was compared with controls receiving placebo to determine the possibility of a retained effect. A second analysis, preserving the advantage of randomization, estimated the potential increase in the time to a CHD event in patients randomized to active treatment compared with patients randomized to placebo, if all patients in both active and placebo groups had fully complied with the trial treatment.

RESULTS

Risk of all CHD while complying with warfarin treatment was associated with a hazard ratio (HR) of 0.75 (95% confidence interval [CI], 0.60-0.94), which was lower than the HR obtained by intention-to-treat analysis (0.79; 95% CI, 0.65-0.96). Regarding fatal cases of CHD, the HR was 0.49 (95% CI, 0.32-0.75) while compliant with warfarin treatment, which is also lower than the HR obtained by intention-to-treat analysis (0.61, 95% CI, 0.43-0.85). Ex-warfarin users had a retained risk reduction of 23% for all CHD (0.77; 95% CI, 0.58-1.02) and of 34% for fatal events (0.66; 95% CI, 0.41-1.04). Expected survival time to a CHD event if patients randomized to warfarin had fully complied with treatment was 1.39 times greater (95% CI, 1.12-1.69) than if patients randomized to placebo had fully complied with placebo, whereas for fatal CHD the relative increase in survival time was 2.04 times greater for the former (95% CI, 1.43-2.86).

CONCLUSIONS

Full compliance with warfarin treatment may lower by 50% the risk of fatal CHD. There is also evidence of a retained effect. These results strengthen previous evidence of the potential benefits of low-intensity oral anticoagulation with warfarin.

摘要

背景

血栓形成预防试验是一项一级预防析因试验，该试验报告华法林和/或阿司匹林可降低冠心病（CHD）风险。本文研究了华法林治疗的依从性（治疗持续时间）以及华法林是否具有持续效应。

方法

将接受华法林治疗时冠心病的风险与所有随机分配至安慰剂组的参与者的冠心病风险进行比较。同时，将既往使用华法林者的冠心病风险与接受安慰剂的对照组进行比较，以确定是否存在持续效应。第二项分析保留了随机化的优势，估计了随机分配至活性治疗组的患者与随机分配至安慰剂组的患者相比，若活性治疗组和安慰剂组的所有患者均完全依从试验治疗，冠心病事件发生时间的潜在增加情况。

结果

接受华法林治疗时所有冠心病的风险与风险比（HR）为0.75（95%置信区间[CI]，0.60 - 0.94）相关，低于意向性分析得出的HR（0.79；95% CI，0.65 - 0.96）。关于冠心病致死病例，接受华法林治疗时HR为0.49（95% CI，0.32 - 0.75），同样低于意向性分析得出的HR（0.61，95% CI，0.43 - 0.85）。既往使用华法林者所有冠心病的风险降低持续存在，降低幅度为23%（0.77；95% CI，0.58 - 1.02），致死事件降低幅度为34%（0.66；95% CI，0.41 - 1.04）。若随机分配至华法林组的患者完全依从治疗，冠心病事件的预期生存时间比随机分配至安慰剂组且完全依从安慰剂治疗的患者长1.39倍（95% CI，1.12 - 1.69），而对于致死性冠心病，前者生存时间的相对增加幅度为后者的2.04倍（95% CI，1.43 - 2.86）。