Lancet. 2000 Apr 15;355(9212):1295-302.
Previous trials of antiplatelet therapy for the prevention of venous thromboembolism have individually been inconclusive, but a meta-analysis of their results indicated reductions in the risks of deep-vein thrombosis and of pulmonary embolism in various high-risk groups. The aim of this large randomised placebo-controlled trial was to confirm or refute these apparent benefits.
During 1992-1998, 148 hospitals in Australia, New Zealand, South Africa, Sweden and the UK randomised 13,356 patients undergoing surgery for hip fracture, and 22 hospitals in New Zealand randomised a further 4088 patients undergoing elective arthroplasty. Study treatment was 160 mg daily aspirin or placebo, started preoperatively and continued for 35 days. Patients received any other thromboprophylaxis thought necessary. Follow-up was of mortality and of in-hospital morbidity up to day 35.
Among the patients with hip fracture, allocation to aspirin produced proportional reductions in pulmonary embolism of 43% (95% CI 18-60; p=0.002) and in symptomatic deep-vein thrombosis of 29% (3-48; p=0.03). Pulmonary embolism or deep-vein thrombosis was confirmed in 105 (1.6%) of 6679 patients assigned aspirin compared with 165 (2.5%) of 6677 assigned placebo, which represents an absolute reduction of 9 (SE 2) per 1000 and a proportional reduction of 36% (19-50; p=0.0003). Similar proportional effects were seen in all major subgroups, including patients receiving subcutaneous heparin. Aspirin prevented 4 (1) fatal pulmonary emboli per 1000 patients (18 aspirin-group vs 43 placebo-group deaths), representing a proportional reduction of 58% (27-76; p=0.002), with no apparent effect on deaths from any other vascular cause (hazard ratio 1.04 [95% CI 0.86-1.26]) or non-vascular cause (1.01 [0.84-1.23]). Deaths due to bleeding were few (13 aspirin vs 15 placebo), but there was an excess of 6 (3) postoperative transfused bleeding episodes per 1000 patients assigned aspirin (p=0.04). Among elective-arthroplasty patients, rates of venous thromboembolism were lower, but the proportional effects of aspirin were compatible with those among patients with hip fracture.
These results, along with those of the previous meta-analysis, show that aspirin reduces the risk of pulmonary embolism and deep-vein thrombosis by at least a third throughout a period of increased risk. Hence, there is now good evidence for considering aspirin routinely in a wide range of surgical and medical groups at high risk of venous thromboembolism.
以往关于抗血小板治疗预防静脉血栓栓塞的试验结果均不明确，但对这些试验结果进行的荟萃分析表明，不同高危人群的深静脉血栓形成和肺栓塞风险有所降低。这项大型随机安慰剂对照试验的目的是证实或反驳这些明显的益处。
1992年至1998年期间，澳大利亚、新西兰、南非、瑞典和英国的148家医院对13356例接受髋部骨折手术的患者进行了随机分组，新西兰的22家医院又对另外4088例接受择期关节成形术的患者进行了随机分组。研究治疗方案为术前开始每日服用160毫克阿司匹林或安慰剂，并持续35天。患者接受任何其他认为必要的血栓预防措施。随访至第35天的死亡率和院内发病率。
在髋部骨折患者中，分配到阿司匹林组的患者，肺栓塞发生率降低了43%（95%可信区间18 - 60；p = 0.002），有症状的深静脉血栓形成发生率降低了29%（3 - 48；p = 0.03）。在分配到阿司匹林组的6679例患者中，有105例（1.6%）发生了肺栓塞或深静脉血栓形成，而分配到安慰剂组的6677例患者中有165例（2.5%）发生，这意味着每1000例患者中绝对风险降低了9例（标准误2），相对风险降低了36%（19 - 50；p = 0.0003）。在所有主要亚组中都观察到了类似的相对效应，包括接受皮下肝素治疗的患者。阿司匹林可预防每1000例患者中4例（1例）致命性肺栓塞（阿司匹林组18例死亡，安慰剂组43例死亡），相对风险降低了58%（27 - 76；p = 0.002），对任何其他血管原因导致的死亡（风险比1.04 [95%可信区间0.86 - 1.26]）或非血管原因导致的死亡（1.01 [0.84 - 1.23]）没有明显影响。因出血导致的死亡很少（阿司匹林组13例，安慰剂组15例），但每1000例分配到阿司匹林组的患者术后输血性出血事件多6例（3例）（p = 0.04）。在择期关节成形术患者中，静脉血栓栓塞发生率较低，但阿司匹林的相对效应与髋部骨折患者相似。
这些结果以及之前的荟萃分析结果表明，在风险增加期间阿司匹林可将肺栓塞和深静脉血栓形成的风险降低至少三分之一。因此，现在有充分的证据支持在广泛的静脉血栓栓塞高危手术和内科患者群体中常规使用阿司匹林。
