LONDON – The new U.S. Preventive Services Task Force draft recommendation for daily low-dose aspirin to reduce the risk of colorectal cancer has been shored up by three large new positive case-control studies presented at the annual congress of the European Society of Cardiology.
The studies weren’t considered by the USPSTF in its deliberations. They’re too new. But the three studies, each with a different methodologic design, collectively included more than 2 million subjects. And each study showed roughly a 30% reduction in the risk of colorectal cancer in daily aspirin users.
©American Heart Association
Dr. Luis A. Garcia Rodriguez presented the three studies, each one an analysis based on data extracted from the Health Improvement Network U.K. primary care database.
The first study included 170,336 new users of low-dose aspirin for primary or secondary prevention of cardiovascular disease and an equal number of individually matched non–aspirin-user controls. This study was designed to simulate enrollment into a placebo-controlled clinical trial of aspirin. During a median 5.1 years of follow-up and after adjustment for numerous potential confounders including smoking, body mass index, and use of nonsteroidal anti-inflammatory drugs, current users of aspirin were found to have a 34% relative risk reduction for colorectal cancer, reported Dr. Garcia Rodriguez, director of the Spanish Center for Pharmacoepidemiologic Research in Madrid.
The second study compared 171,527 new users of low-dose aspirin with 149,597 new users of acetaminophen. Acetaminophen users were selected as a control group to minimize any healthy-user bias arising from differences between aspirin users and nonusers in the first study. In study two, over a median 5.8 years of follow-up, the aspirin users had an adjusted 29% relative risk reduction for colorectal cancer.
Dr. Luis A. Garcia Rodriguez
The third study used a nested case-control methodology. Dr. Garcia Rodriguez and his associates began with a pool of 1,935,801 patients naive to daily low-dose aspirin. They then identified the individuals within that cohort who were diagnosed with colorectal cancer during 7.5 years of follow-up, matched them to 20,000 controls by age and gender, and determined who had initiated daily low-dose aspirin for cardiovascular prevention during the follow-up period. The daily aspirin users proved to be at an adjusted 31% lower risk of colorectal cancer than nonusers.
The fact that a consistent protective effect against colorectal cancer was seen in all three studies argues against the findings being explainable on the basis of selection bias, Dr. Garcia Rodriguez asserted.
In all three studies, the protective effect against colorectal cancer was greater in patients on low-dose aspirin for secondary rather than primary cardiovascular prevention. Patients taking aspirin for secondary prevention in studies one, two, and three had relative risk reductions in colorectal cancer of 40%, 38%, and 39%, respectively, compared with non–aspirin-using controls. Among individuals on aspirin for primary cardiovascular prevention, the relative risk reductions for colorectal cancer were 29%, 22%, and 25% across the three studies.
The studies were funded by Bayer Pharma. Dr. Garcia Rodriguez has served as an advisory board member for the company.
This article was updated 10/14/2015.