Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials
Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials
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DOI：
10.1016/s0140-6736(11)61720-0
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发表时间：
2012-04-28
期刊：
影响因子：
168.9
通讯作者：
Meade, Tom W.
中科院分区：
文献类型：
--
作者：
Rothwell, Peter M.;Price, Jacqueline F.;Meade, Tom W.
每日服用阿司匹林可降低癌症死亡的长期风险。然而，短期效果不太确定，特别是在女性中，对癌症发病率的影响在很大程度上是未知的，一级预防的风险和益处的时间过程也不清楚。我们研究了癌症死亡的所有试验中，每日阿司匹林与控制和低剂量阿司匹林对癌症发病率和其他结果的影响，在一级prevention.Methods的试验中的时间过程中，我们研究了个体患者的数据，从随机试验中每日阿司匹林与不阿司匹林预防血管事件。在所有合格试验中评估了癌症死亡、所有非血管性死亡、血管性死亡和所有死亡。在低剂量阿司匹林的一级预防试验中，我们还建立了对癌症事件、主要血管事件和主要颅外出血影响的时间过程，并按年龄、性别和吸烟状况分层。（562 vs 664例死亡;比值比[OR] 0.85，95% CI 0.76 - 0.96，p = 0.008; 34项试验，69224例受试者），尤其是5年后（92 vs 145; OR 0.63，95% CI 0.49 - 0.82，p = 0.0005），导致总体非血管性死亡较少（1021 vs 1173; OR 0.88，95% CI 0.78 - 0.96，p = 0.003; 51项试验，77 549例受试者）。在一级预防试验中，非血管性死亡的减少占预防的96例死亡中的87例（91%）。在6项每日低剂量阿司匹林的一级预防试验中，（35535名参与者），阿司匹林从3年开始降低癌症发病率女性（324 vs 421例; OR 0.76，95% CI 0.66 - 0.88，p = 0.0003）（132 vs 176; OR 0.75，95% CI 0.59 - 0.94，p = 0.01）和男性（192 vs 245; OR 0.77，95% CI 0.63 - 0.93，p = 0.008）。阿司匹林降低的主要血管事件风险最初被增加的大出血风险抵消，但对两种结局的影响随着随访时间的增加而减少，从3年开始仅降低了癌症风险（绝对降低3.13 [95%CI 1.44 - 4.82]/1000例患者/年）。与对照组相比，阿司匹林组的颅外大出血病死率也较低（8/203对15/132; OR 0.32，95%CI 0.12 - 0.83，p = 0.009）。解释除了先前报道的阿司匹林降低癌症死亡的长期风险外，长期使用可短期降低癌症发病率和死亡率，降低颅外大出血风险，且病死率低，增加每日服用阿司匹林预防癌症的理由。
Background Daily aspirin reduces the long-term risk of death due to cancer. However, the short-term effect is less certain, especially in women, effects on cancer incidence are largely unknown, and the time course of risk and benefit in primary prevention is unclear. We studied cancer deaths in all trials of daily aspirin versus control and the time course of effects of low-dose aspirin on cancer incidence and other outcomes in trials in primary prevention.Methods We studied individual patient data from randomised trials of daily aspirin versus no aspirin in prevention of vascular events. Death due to cancer, all non-vascular death, vascular death, and all deaths were assessed in all eligible trials. In trials of low-dose aspirin in primary prevention, we also established the time course of effects on incident cancer, major vascular events, and major extracranial bleeds, with stratification by age, sex, and smoking status.Results Allocation to aspirin reduced cancer deaths (562 vs 664 deaths; odds ratio [OR] 0.85, 95% CI 0.76-0.96, p=0.008; 34 trials, 69 224 participants), particularly from 5 years onwards (92 vs 145; OR 0.63, 95% CI 0.49-0.82, p=0.0005), resulting in fewer non-vascular deaths overall (1021 vs 1173; OR 0.88, 95% CI 0.78-0.96, p=0.003; 51 trials, 77 549 participants). In trials in primary prevention, the reduction in non-vascular deaths accounted for 87 (91%) of 96 deaths prevented. In six trials of daily low-dose aspirin in primary prevention (35 535 participants), aspirin reduced cancer incidence from 3 years onwards (324 vs 421 cases; OR 0.76, 95% CI 0.66-0.88, p=0.0003) in women (132 vs 176; OR 0.75, 95% CI 0.59-0.94, p=0.01) and in men (192 vs 245; OR 0.77, 95% CI 0.63-0.93, p=0.008). The reduced risk of major vascular events on aspirin was initially off set by an increased risk of major bleeding, but effects on both outcomes diminished with increasing follow-up, leaving only the reduced risk of cancer (absolute reduction 3.13 [95% CI 1.44-4.82] per 1000 patients per year) from 3 years onwards. Case-fatality from major extracranial bleeds was also lower on aspirin than on control (8/203 vs 15/132; OR 0.32, 95% CI 0.12-0.83, p=0.009).Interpretation Alongside the previously reported reduction by aspirin of the long-term risk of cancer death, the short-term reductions in cancer incidence and mortality and the decrease in risk of major extracranial bleeds with extended use, and their low case-fatality, add to the case for daily aspirin in prevention of cancer.