Low-dose aspirin taken long term reduced incidence of, mortality from colorectal cancer

Long-term use of aspirin taken at doses of at least 75 mg reduced the incidence of colorectal cancer by about one-quarter and decreased mortality from the disease by more than one-third.

Researchers from the University of Oxford in the United Kingdom conducted a study to examine the long-term effectiveness of lower doses (75 mg to 300 mg daily) of aspirin on colorectal cancer incidence and mortality. They followed five randomized trials for 20 years.

The researchers assessed studies on aspirin, originally conducted to examine prevention of vascular disease, to determine the effects of aspirin on colorectal cancer. Four trials of aspirin vs. placebo had a mean duration of 6 years. There were 14,033 patients.

During a median follow-up of 18.3 years, 2.8% of patients had colorectal cancer. In a pooled analysis of individual patient data, aspirin reduced the 20-year risk for colon cancer by 24% (HR=0.76; 95% CI, 0.60-0.96) and mortality from colon cancer by 35% (HR=0.65; 95% CI, 0.48-0.88).

Results were consistent across trials, and there was no increased benefit for doses of more than 75 mg/day, with an absolute reduction of 1.76% (95% CI, 0.61-2.91) for the 20-year absolute risk for any fatal colorectal cancer after 5 years of treatment with 75 mg to 300 mg of aspirin per day.

Reductions in incidence and death colorectal cancer consisted almost entirely of reductions in risk for proximal colon cancer of about 70%; however, there was no observed effect on distal colon cancer and only a small effect on rectal cancer.

In a study published in The Lancet by Atkin and colleagues in May, findings showed that a one-off sigmoidoscopy decreased colorectal cancer mortality by 43% in those screened and reduced incidence by one-third.

According to the researchers, the findings from this new study may help push the recently finely balanced risk-benefit debate regarding long-term aspirin use back toward favoring benefit.

“The five trials we studied all predated endoscopic screening for adenomas, which also reduces colorectal cancer incidence and mortality, and might therefore reduce the absolute benefit of aspirin. However, the suggestion of a particular effect of aspirin on more aggressive and rapidly growing tumors might allow less frequent screening, and the prevention of proximal colonic cancers by aspirin, which would not be identified by sigmoidoscopy, is clearly important. It is therefore probable that these two approaches to prevention of colorectal cancer will be synergistic,” Peter Rothwell, MD, professor of Clinical Neurology at the University of Oxford, said in a press release.

“Our findings suggest that long-term low-dose aspirin treatment and sigmoidoscopy screening would combine to substantially reduce cancer incidence in all parts of the colon and rectum,” Rothwell added.

He said the UK government recently announced the launch of a nationwide sigmoidoscopy screening program during the 2010 Conservative Party Conference.

“The new findings on the effect of low-dose aspirin should be included in advice given to the public on the screening program and other approaches to preventing colorectal cancer,” Rothwell said.

The findings of this study will incite clinicians to turn to primary prevention of colorectal cancer by aspirin at least in high-risk populations, according to Robert Benamouzig, MD, department of gastroenterology, and Bernard Uzzan, MD, department of pharmacology, at Avicenne Hospital, in Bobigny, France.

“Specific guidelines for aspirin chemoprevention would be the next logical step,” they said in an accompanying editorial.

For more information:

Atkin WS. Lancet. 2010;375:1624-1633.
Benamouzig R. Lancet. 2010;doi:10.1016/S0140-6736(10)61509-7.
Rothwell PM. Lancet. 2010;doi:10.1016/S0140-6736(10)61543-7.

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