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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
Summary
Background
Daily
aspirin reduces the long-term risk of death due to cancer. However, the
short-term effect is less certain, especially in women, effects on
cancer incidence are largely unknown, and the time course of risk and
benefit in primary prevention is unclear. We studied cancer deaths in
all trials of daily aspirin versus control and the time course of
effects of low-dose aspirin on cancer incidence and other outcomes in
trials in primary prevention.
Interpretation
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
We
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, we 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.
Results
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).
Interpretation
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.
Funding
None.
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