Taking at least 75 mg of aspirin daily for several years reduces significantly the long-term risks of developing colorectal cancer and of dying from the disease, according to an analysis of five randomized trials involving more than 14,000 patients.
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Patients allocated to take at least 75 mg aspirin for 5 years or more had a highly significant reduction of about 70% in the risk of proximal colon cancer. They also had a significantly reduced incidence of rectal cancer, researchers reported.
The 20-year incidence of colon cancer was reduced by 24% (hazard ratio 0.76) and 20-year mortality by 35% (HR 0.65) in patients who took aspirin and were compared with a control group in pooled data from four of the trials, reported Dr. Peter M. Rothwell, a professor of clinical neurology and founder of the stroke prevention research unit at the University of Oxford, U.K., and his colleagues.
Allocation to aspirin in those trials did not, however, reduce the overall risk of developing rectal cancer (HR 0.90), according to findings published online in the Oct. 22 issue of The Lancet.
All of the trials were designed to look at prevention of vascular events, not colorectal cancer specifically. The four pooled trials compared aspirin with either placebo or no treatment. The new analysis shows that 391 of 14,033 patients (2.8%) developed colon cancer after a median of 6 years of scheduled treatment and at a median follow-up of 18.3 years.
Of note was a finding that in studies for which data were available, patients allocated to receive aspirin had a significantly reduced risk of cancer of the proximal colon (HR 0.45), but not the distal colon (HR 1.10). Similarly, patients on aspirin had a significantly reduced risk of fatal proximal colon cancers (HR 0.34), but not fatal distal colon cancers (HR 1.21), the investigators said (Lancet 2010 Oct. 22 [doi:10.1016/S0140-6736(10)61543-7]).
The risk reduction increased with scheduled duration of treatment; patients allocated to take aspirin for at least 5 years had a highly significant reduction of about 70% in the risk of proximal colon cancer (HR 0.35). They also had a significantly reduced incidence of rectal cancer but not distal colon cancer.
Furthermore, no increase in benefit was seen with doses above 75 mg daily, according to an analysis of data from the fifth study and one of the four controlled studies, both of which compared various doses of aspirin. An absolute reduction of 1.76% in 20-year risk of any fatal colorectal cancer was seen with doses ranging from 75 mg daily to 300 mg daily; it persisted when the analysis was limited to patients allocated to 75 mg daily. In one study, which compared a 30 mg and 283 mg daily dose, however, mortality was significantly higher with the 30 mg dose (odds ratio 2.02).
In a previous report of data from two of the trials in the current analysis, the investigators showed that the 20-year incidence of colorectal cancer was reduced by 30% in patients who used high-dose aspirin for 5 years. The current findings are important in that they show a similar effect with doses as low as 75 mg daily, they said.
The study has some potential limitations, including the possibility that trial participants had more investigations because adverse treatment effects, and therefore may have had an earlier diagnosis of colorectal adenoma or cancer than they would have had otherwise. Also, the number of cancers in the study that compared 30-mg and 283-mg doses was small, which limits the certainty of the effect.
Nonetheless, the finding of an approximately 1.5% reduction in absolute long-term risk of colorectal cancer does have implications for clinical practice, the investigators said. “In patients with an established indication for long-term antiplatelet treatment, such as in secondary prevention of vascular disease, this additional benefit will favor treatment with aspirin over other antiplatelet drugs, assuming that other drugs do not afford similar benefit,” they wrote.
Also, in light of the recently “finely balanced” risk-benefit debate over long-term benefits vs. major bleeding risk with aspirin therapy to reduce the risk of ischemic vascular events, the current findings might “tip the balance” back to favoring treatment, they argued.
“The five trials we studied all predated endoscopic screening for adenomas, which also reduced 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 cancer by aspirin, which would not be identified by sigmoidoscopy screening and for which colonoscopy screening is only partly effective, is clearly important,” they wrote.