Sutcliffe Paul, Connock Martin, Gurung Tara, Freeman Karoline, Johnson Samantha, Ngianga-Bakwin Kandala, Grove Amy, Gurung Binu, Morrow Sarah, Stranges Saverio, Clarke Aileen
Warwick Medical School, University of Warwick, Coventry, Warwickshire, England.
PLoS One. 2013 Dec 5;8(12):e81970. doi: 10.1371/journal.pone.0081970. eCollection 2013.
Aspirin has been recommended for primary prevention of cardiovascular disease (CVD) and cancer, but overall benefits are unclear. We aimed to use novel methods to re-evaluate the balance of benefits and harms of aspirin using evidence from randomised controlled trials, systematic reviews and meta-analyses.
Data sources included ten electronic bibliographic databases, contact with experts, and scrutiny of reference lists of included studies. Searches were undertaken in September 2012 and restricted to publications since 2008. Of 2,572 potentially relevant papers 27 met the inclusion criteria. Meta-analysis of control arms to estimate event rates, modelling of all-cause mortality and L'Abbé plots to estimate heterogeneity were undertaken. Absolute benefits and harms were low: 60-84 major CVD events and 34-36 colorectal cancer deaths per 100,000 person-years were averted, whereas 46-49 major bleeds and 68-117 gastrointestinal bleeds were incurred. Reductions in all-cause mortality were minor and uncertain (Hazard Ratio 0.96; 95% CI: 0.90-1.02 at 20 years, Relative Risk [RR] 0.94, 95% CI: 0.88-1.00 at 8 years); there was a non-significant change in total CVD (RR 0.85, 95% CI: 0.69-1.06) and change in total cancer mortality ranged from 0.76 (95% CI: 0.66-0.88) to 0.93 (95% CI: 0.84-1.03) depending on follow-up time and studies included. Risks were increased by 37% for gastrointestinal bleeds (RR 1.37, 95% CI: 1.15-1.62), 54%-66% for major bleeds (Rate Ratio from IPD analysis 1.54, 95% CI: 1.30-1.82, and RR 1.62, 95% CI: 1.31-2.00), and 32%-38% for haemorrhagic stroke (Rate Ratio from IPD analysis 1.32; 95% CI: 1.00-1.74; RR 1.38; 95% CI: 1.01-1.82).
Findings indicate small absolute effects of aspirin relative to the burden of these diseases. When aspirin is used for primary prevention of CVD the absolute harms exceed the benefits. Estimates of cancer benefit rely on selective retrospective re-analysis of RCTs and more information is needed.
阿司匹林已被推荐用于心血管疾病（CVD）和癌症的一级预防，但总体益处尚不清楚。我们旨在使用新方法，利用随机对照试验、系统评价和荟萃分析的证据，重新评估阿司匹林的利弊平衡。
数据来源包括十个电子文献数据库、与专家的联系以及对纳入研究参考文献列表的审查。检索于2012年9月进行，仅限于2008年以来的出版物。在2572篇可能相关的论文中，27篇符合纳入标准。对对照组进行荟萃分析以估计事件发生率，对全因死亡率进行建模，并使用L'Abbé图估计异质性。绝对益处和危害较低：每10万人年可避免60 - 84例主要心血管疾病事件和34 - 36例结直肠癌死亡，而会发生46 - 49例主要出血和68 - 117例胃肠道出血。全因死亡率的降低幅度较小且不确定（20年时风险比0.96；95%置信区间：0.90 - 1.02；8年时相对风险[RR] 0.94，95%置信区间：0.88 - 1.00）；总心血管疾病无显著变化（RR 0.85，95%置信区间：0.69 - 1.06），总癌症死亡率的变化范围为0.76（95%置信区间：0.66 - 0.88）至0.93（95%置信区间：0.84 - 1.03），具体取决于随访时间和纳入的研究。胃肠道出血风险增加37%（RR 1.37，95%置信区间：1.15 - 1.62），主要出血风险增加54% - 66%（个体患者数据[IPD]分析的率比1.54，95%置信区间：1.30 - 1.82；RR 1.62，95%置信区间：1.31 - 2.00），出血性中风风险增加32% - 38%（IPD分析的率比1.32；95%置信区间：1.00 - 1.74；RR 1.38；95%置信区间：1.01 - 1.82）。
研究结果表明，相对于这些疾病的负担，阿司匹林的绝对效果较小。当阿司匹林用于心血管疾病的一级预防时，绝对危害超过益处。对癌症益处的估计依赖于对随机对照试验的选择性回顾性重新分析，还需要更多信息。
