Meade T W, Wilkes H C, Stirling Y, Brennan P J, Kelleher C, Browne W
MRC Epidemiology and Medical Care Unit, Northwick Park Hospital, Harrow, Middlesex, U.K.
Eur Heart J. 1988 Aug;9(8):836-43. doi: 10.1093/oxfordjournals.eurheartj.a062576.
We report the pilot stage of a double-blind randomized controlled trial of low dose warfarin in the primary prevention of ischaemic heart disease (IHD) in men at high risk. The first objective was to see if levels of factor VII coagulant activity, VIIc, could be reduced without undue difficulty from a mean level of about 115% to about 70% (the level in patients on conventional warfarin doses being about 30%). This was accomplished with a mean daily dose of 4.6 mg warfarin. The international normalized ratio (INR) corresponding to a VIIc value of 70% was about 1.5. The second objective was to assess the risk of bleeding associated with the intended level of anticoagulation. There was no significant excess in the number of actively treated men ever reporting nose bleeds, possible haematuria, rectal bleeding or bruising, although there may have been an increase in the frequency of rectal bleeding in men who did report this symptom. The third objective was to establish the willingness of patients to take part in a trial of this kind. Of those invited to the initial screening examination, 72% attended. Of those invited to enter the treatment phase of the trial, 71% did so. Compliance with trial treatment was at a very high level. The rate of withdrawal from randomized treatment was within acceptable limits, at about 15% over a three- or four-year period. The scientific case for a full trial is strong and the pilot trial shows that it could be accomplished.
我们报告了一项低剂量华法林用于高危男性缺血性心脏病（IHD）一级预防的双盲随机对照试验的试点阶段。首要目标是查看是否能相对轻松地将凝血因子VII促凝活性（VIIc）水平从约115%的平均水平降至约70%（接受常规华法林剂量治疗的患者该水平约为30%）。这一目标通过平均每日4.6毫克的华法林剂量得以实现。与VIIc值70%相对应的国际标准化比值（INR）约为1.5。第二个目标是评估与预期抗凝水平相关的出血风险。积极接受治疗的男性中，报告鼻出血、可能的血尿、直肠出血或瘀伤的人数并无显著增加，不过报告有直肠出血症状的男性中，直肠出血频率可能有所上升。第三个目标是确定患者参与此类试验的意愿。在受邀参加初始筛查检查的人群中，72%的人前来就诊。在受邀进入试验治疗阶段的人群中，71%的人照做了。对试验治疗的依从性处于非常高的水平。随机治疗的退出率在可接受范围内，在三到四年的时间里约为15%。开展全面试验的科学依据充分，试点试验表明该试验是可以完成的。
