Our analysis included all five large randomised trials of daily aspirin (鈮?5 mg daily) versus control for the prevention of vascular events in the UK. Electronic and paper records were reviewed for all patients with incident cancer. The effect of aspirin on risk of metastases at presentation or on subsequent follow-up (including post-trial follow-up of in-trial cancers) was stratified by tumour histology (adenocarcinoma vs other) and clinical characteristics.
Of 17鈥?85 trial participants, 987 had a new solid cancer diagnosed during mean in-trial follow-up of 6路5 years (SD 2路0). Allocation to aspirin reduced risk of cancer with distant metastasis (all cancers, hazard ratio [HR] 0路64, 95%CI 0路48-0路84, p=0路001; adenocarcinoma, HR 0路54, 95%CI 0路38-0路77, p=0路0007; other solid cancers, HR 0路82, 95%CI 0路53-1路28, p=0路39), due mainly to a reduction in proportion of adenocarcinomas that had metastatic versus local disease (odds ratio 0路52, 95%CI 0路35-0路75, p=0路0006). Aspirin reduced risk of adenocarcinoma with metastasis at initial diagnosis (HR 0路69, 95%CI 0路50-0路95, p=0路02) and risk of metastasis on subsequent follow-up in patients without metastasis initially (HR 0路45, 95%CI 0路28-0路72, p=0路0009), particularly in patients with colorectal cancer (HR 0路26, 95%CI 0路11-0路57, p=0路0008) and in patients who remained on trial treatment up to or after diagnosis (HR 0路31, 95%CI 0路15-0路62, p=0路0009). Allocation to aspirin reduced death due to cancer in patients who developed adenocarcinoma, particularly in those without metastasis at diagnosis (HR 0路50, 95%CI 0路34-0路74, p=0路0006). Consequently, aspirin reduced the overall risk of fatal adenocarcinoma in the trial populations (HR 0路65, 95%CI 0路53-0路82, p=0路0002), but not the risk of other fatal cancers (HR 1路06, 95%CI 0路84-1路32, p=0路64; difference, p=0路003). Effects were independent of age and sex, but absolute benefit was greatest in smokers. A low-dose, slow-release formulation of aspirin designed to inhibit platelets but to have little systemic bioavailability was as effective as higher doses.
That aspirin prevents distant metastasis could account for the early reduction in cancer deaths in trials of daily aspirin versus control. This finding suggests that aspirin might help in treatment of some cancers and provides proof of principle for pharmacological intervention specifically to prevent distant metastasis.
None.