title: 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.
abstract: 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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  None.
authors.affiliation: Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience, University of Oxford, UK. peter.rothwell@clneuro.ox.ac.uk
authors.forename: Peter M
authors.initials: PM
authors.lastname: Rothwell
authors.forename: Jacqueline F
authors.initials: JF
authors.lastname: Price
authors.forename: F Gerald R
authors.initials: FG
authors.lastname: Fowkes
authors.forename: Alberto
authors.initials: A
authors.lastname: Zanchetti
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Roncaglioni
authors.forename: Gianni
authors.initials: G
authors.lastname: Tognoni
authors.forename: Robert
authors.initials: R
authors.lastname: Lee
authors.forename: Jill F F
authors.initials: JF
authors.lastname: Belch
authors.forename: Michelle
authors.initials: M
authors.lastname: Wilson
authors.forename: Ziyah
authors.initials: Z
authors.lastname: Mehta
authors.forename: Tom W
authors.initials: TW
authors.lastname: Meade
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D009369:Neoplasms / Q000453:epidemiology* / Q000401:mortality / Q000517:prevention & control*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment
chemical_list: D000970:Antineoplastic Agents; D010975:Platelet Aggregation Inhibitors; D001241:Aspirin