Daily aspirin may reduce cancer incidence, prevent metastases

Three related studies bolster the case for daily aspirin for cancer prevention, indicating that it may have a preventive effect after three years, as well as reduce future metastases, while having little impact on increased bleeding risk in the long term.

The studies, on short-term effects,metastases and observational versus randomized trials, appeared March 21 in The Lancet and The Lancet: Oncology.

The first study examined 51 randomized trials of daily aspirin versus no aspirin prescribed to prevent vascular events. All the trials looked at death due to cancer, all non-vascular death, vascular death and all-cause deaths.

Aspirin reduced cancer deaths (odds ratio [OR], 0.85; P=0.008; 34 trials, 69,224 participants), particularly at five years or more (OR, 0.63; P=0.0005), resulting in fewer non-vascular deaths overall (OR, 0.88; P=0.003; 51 trials; 77,549 participants).

Primary prevention trials showed that a 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 three years onward (OR, 0.76; P=0.0003) in women (OR, 0.75; P=0.01) and in men (OR, 0.77; P=0.008).

The reduced risk of major vascular events on aspirin was initially offset by an increased risk of major bleeding, the authors noted. But effects on both outcomes diminished with increasing follow-up, leaving only the reduced risk of cancer (absolute reduction, 3.13 per 1,000 patients per year) from three years onward. Case-fatality from major extracranial bleeds was also lower with aspirin (OR, 0.32; P=0.009).

The authors noted that aspirin reduced cancer deaths by nearly 40% after five years, reduced the risk of all vascular death, reduced the incidence of cancer by 25% after three years, and reduced cancer incidence in women.

“The demonstration of overall benefit from aspirin in the shorter-term, and the finding that the increased risk of major extracranial bleeding does not persist with extended use, add to the case for long-term use of aspirin for cancer prevention in middle age, in addition to appropriate dietary and lifestyle interventions,” the authors concluded.

The second study indicated that, as well as reducing the long-term risk of some cancers, aspirin also prevents distant cancer metastases. It included five large randomized trials of 75 mg or more of daily aspirin for the prevention of vascular events.

Of 17,285 trial participants, 987 had a new solid cancer diagnosed during mean in-trial follow-up of 6.5 years. Aspirin reduced risk of cancer with distant metastasis (all cancers, hazard ratio [HR], 0.64; P=0.001; adenocarcinoma, HR, 0.54; P=0.0007; and other solid cancers, HR, 0.82; P=0.39). The reduction was mainly due to a reduction in proportion of adenocarcinomas that were metastatic versus local (OR, 0.52; P=0.0006).

Aspirin reduced risk of adenocarcinoma with metastasis at initial diagnosis (HR, 0.69; P=0.02) and risk of metastasis on subsequent follow-up in patients without metastasis initially (HR, 0.45; P=0.0009), particularly in patients with colorectal cancer (HR, 0.26; P=0.0008) and in patients who remained on trial treatment up to or after diagnosis (HR, 0.31; P=0.0009). Aspirin reduced death due to cancer in patients who developed adenocarcinoma, particularly in those without metastasis at diagnosis (HR, 0.50; P=0.0006).

Consequently, aspirin reduced the overall risk of fatal adenocarcinoma (HR, 0.65; P=0.0002), but not the risk of other fatal cancers (HR, 1.06; P=0.64; difference, P=0.003).

That aspirin prevents distant metastasis could account for the early reduction in cancer deaths in trials of daily aspirin versus control, the authors wrote.

The third study compared outcomes for observational versus randomized trials. Observational studies suggest that regular use of aspirin is associated with a reduction in the long-term risk of several cancers and the risk of distant metastasis. Colorectal cancer was used as the test case in this study.

In case-control studies, regular use of aspirin was associated with reduced risk of colorectal cancer (pooled OR, 0.62; P<0.0001, 17 studies), with little heterogeneity (P=0.13) in effect between studies, and good agreement with the effect of daily aspirin use on 20-year risk for death due to colorectal cancer from the randomized trials (OR, 0.58; P=0.0002; P=0.45 for heterogeneity). Similarly consistent reductions were seen in risks of esophageal, gastric, biliary and breast cancer.

Overall, estimates of the effect of aspirin on individual cancers in case-control studies were highly correlated with those in randomized trials (r²=0.71; P=0.0006), with largest effects on risk of gastrointestinal cancers (case-control studies, OR, 0.62; P<0.0001, 41 studies; randomized trials, OR, 0.54; P<0.0001).

Estimates of effects in cohort studies were similar when analyses were stratified by frequency and duration of aspirin use, were based on updated assessments of use during follow-up, and were appropriately adjusted for baseline characteristics.

“We now have shown that case-control studies yield estimates of the effect of aspirin on risk of colorectal cancer that are in close agreement with those from the trials,” the authors wrote.

An online commentary pointed out that the studies “show quite convincingly that aspirin seems to reduce cancer incidence and death across different subgroups and cancer sites, with an apparent delayed effect. Additionally, aspirin's known benefits in vascular disease and known toxic effects in causing major bleeding emerged in the short term, but diminished over time. Thus, for most individuals, the risk-benefit calculus of aspirin seems to favour aspirin's long-term anticancer benefit.”