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 - Early Online Publication, 03/29/2012
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
- Individual patient data from randomised trials of daily aspirin versus no aspirin in prevention of vascular events were reviewed.
- 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, the time course of effects on incident cancer, major vascular events, and major extracranial bleeds, with stratification by age, sex, and smoking status were established.
- 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).