Low-dose Aspirin and Cancer Mortality: A Meta-analysis of Randomized Trials

OBJECTIVE: Low-dose aspirin is a common strategy for preventing cardiovascular disease and associated mortality. A recent individual patient data meta-analysis of 8 trials of low- and high-dose aspirin, with long-term follow-up, found important reductions in cancer mortality. We aimed to determine whether cancer mortality also is reduced by low-dose aspirin in the shorter term. METHODS: We conducted a comprehensive search of 10 electronic databases up to December 2011. We conducted a meta-analysis using data from all randomized clinical trials evaluating low-dose (75-325 mg) daily aspirin. We extracted data on non-cardiovascular disease mortality and cancer mortality. We pooled studies using a random-effects model and conducted a meta-regression. We supplemented this with a cumulative meta-analysis and trial sequential monitoring analysis. RESULTS: Twenty-three randomized studies reported on nonvascular death. There were 944 nonvascular deaths of 41,398 (2.28%) patients receiving low-dose aspirin and 1074 nonvascular deaths of 41,470 (2.58%) patients not receiving aspirin therapy. The relative risk of nonvascular death was 0.88 (95% confidence interval [CI], 0.81-0.96, I(2) = 0%). Eleven trials included data evaluating cancer mortality involving 16,066 patients. There were 162 of 7998 (2.02%) and 210 of 8068 (2.60%) cancer deaths among low-dose aspirin users versus non-aspirin users, respectively, reported over an average follow-up of 2.8 years. The relative risk of cancer mortality was 0.77 (95% CI, 0.63-0.95, I(2) = 0%). Studies demonstrated a significant treatment effect after approximately 4 years of follow-up. The optimal information size analysis showed that a sufficient number of patients had been randomized to provide convincing evidence of a preventive role of low-dose aspirin in nonvascular deaths. CONCLUSION: Nonvascular deaths, including cancer deaths, are reduced with low-dose aspirin.