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
The Lancet, 05/14/2012
Rothwell PM et al. – 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.Methods
- Authors 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, authors 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.
- 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 offset 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).