Meade T W, Roderick P J, Brennan P J, Wilkes H C, Kelleher C C
MRC Epidemiology and Medical Care Unit, Medical College of St Bartholomew's Hospital, London, United Kingdom.
Thromb Haemost. 1992 Jul 6;68(1):1-6.
Data from the early stages of the thrombosis prevention trial (TPT) have been used to establish and quantify the risk of extracranial bleeding due to low dose aspirin (75 mg) and low intensity oral anticoagulation with warfarin (international normalised ratio, INR, 1.5) singly or in combination, in men aged between 45 and 69 who are at high risk of ischaemic heart disease (IHD). The design of the trial is factorial, the four treatments being combined low dose aspirin and low intensity anticoagulation (WA), low intensity anticoagulation alone (W), low dose aspirin alone (A) and double placebo treatment (P). The trial is being carried out through the Medical Research Council's General Practice Research Framework, with participating practices throughout the United Kingdom. Results are based on the first 3,667 men entered. The risk of major gastrointestinal bleeding due to active treatment is probably about 1 in 500 man-years of treatment, there currently being no difference between the three active regimes (WA, W, A). Intermediate and minor bleeding episodes occur more frequently with WA than with W or A on their own, the excess being mainly due to minor nose bleeds and bruises. In turn, both W and A on their own cause more such minor episodes than placebo treatment, P. There is no evidence that any of the three active regimens increases the risk of peptic ulceration, nor do they increase reports of indigestion. Aspirin increases reports of constipation and reduces reports of blurred vision. Minor bleeding occurs less frequently in smokers than in non-smokers but is not influenced by age. The antithrombotic regimes used are feasible and acceptable.
血栓预防试验（TPT）早期阶段的数据已用于确定和量化低剂量阿司匹林（75毫克）以及低强度口服华法林抗凝治疗（国际标准化比值，INR，1.5）单独或联合使用时，在年龄介于45至69岁、患有缺血性心脏病（IHD）高风险的男性中发生颅外出血的风险。该试验采用析因设计，四种治疗方法分别为联合低剂量阿司匹林和低强度抗凝治疗（WA）、单独低强度抗凝治疗（W）、单独低剂量阿司匹林治疗（A）以及双重安慰剂治疗（P）。该试验通过医学研究委员会的全科医学研究框架开展，参与试验的医疗机构遍布英国。结果基于最初纳入的3667名男性。积极治疗导致的严重胃肠道出血风险可能约为每治疗1000人年中有1例，目前三种积极治疗方案（WA、W、A）之间并无差异。与单独使用W或A相比，WA导致的中度和轻度出血事件更为频繁，多出的部分主要是由于轻度鼻出血和瘀伤。反过来，单独使用W和A导致的此类轻度事件都比安慰剂治疗P更多。没有证据表明三种积极治疗方案中的任何一种会增加消化性溃疡的风险，也不会增加消化不良的报告。阿司匹林会增加便秘报告并减少视力模糊的报告。轻度出血在吸烟者中比在非吸烟者中发生频率更低，但不受年龄影响。所使用的抗血栓治疗方案是可行且可接受的。
