Does the long-term use of aspirin decrease the risk of death due to cancer?

Abstract

Question: Does the long-term use of acetylsalicylic acid (ASA) decrease the risk of death due to cancer? Design: Pooled analysis. Data source: Cochrane Collaboration, Database of Systematic reviews, PubMed and Embase. Study selection: Individual patient data from all randomized trials of daily ASA versus no ASA with a mean duration of scheduled trial treatment of 4 years or longer were used to determine the effect of allocation to ASA on risk of cancer death in relation to scheduled duration of trial treatment for gastrointestinal (GI) and non-GI cancers. Results: In 8 eligible trials (25 570 patients, 674 cancer-related deaths), allocation to ASA reduced the risk of death due to cancer (pooled odds ratio [OR] 0.79, 95% confidence interval [CI] 0.68–0.92, p = 0.003). On analysis of individual patient data, which were available from 7 trials (23 535 patients, 657 cancer-related deaths), the benefit was apparent only after 5 years’ follow-up (all cancers, hazard ratio [HR] 0.66, 95% CI 0.50–0.87; GI cancers, 0.46, 95% CI 0.27–0.77; both p = 0.003). The 20-year risk of cancer death (deaths in 12 659 patients in 3 trials) remained lower in the ASA groups than in the control groups (all solid organ cancers, HR 0.80, 95% CI 0.72–0.88, p < 0.001; GI cancers, HR 0.65, 95% CI 0.54–0.78, p < 0.001), and benefit increased (interaction p = 0.01) with scheduled duration of trial treatment (≥ 7.5 years: all solid cancers, HR 0.69, 95% CI 0.54–0.88, p = 0.003; GI cancers, HR 0.41, 95% CI 0.26–0.66, p < 0.001). The latent period before an effect on deaths could be observed was about 5 years for esophageal, pancreatic, brain and lung cancer, but was longer for stomach, colorectal and prostate cancer. For lung or esophageal cancer, the benefit was confined to adenocarcinomas, and the overall effect on 20-year risk of cancer-related death was greatest for adneocarcinomas (HR 0.66, 95% CI 0.56–0.77, p < 0.001). The benefit was unrelated to ASA dose (75 mg or higher), sex or smoking, but was increased with age; the absolute reduction in 20-year risk of cancer-related death reached 7.08% at age 65 years and older. Conclusion: Daily ASA reduced deaths due to several common cancers during and after the trials. The benefit increased with duration of treatment and was consistent across the different study populations. These findings have implications for guidelines on use of ASA and for understanding carcinogenesis and its susceptibility to drug intervention.