Benefits Add Up for Regular Aspirin Use
Published: Aug 5, 2014 | Updated: Aug 6, 2014
Discussant: Joseph Chao, MD.
Average-risk adults in the general population who used aspirin regularly for at least 5 years had a lower risk of cancer, myocardial infarction (MI), stroke, and premature death, according to a comprehensive review of potential benefits and harms.
The relative risk reduction was between 7% for women and 9% for men for all cancer and cardiovascular events combined over a 10-year period. Long-term regular aspirin use was associated with a 4% reduction in the risk of premature death over 20 years.
The benefits appeared to increase with the duration of aspirin use but not with the dose, Jack Cuzick, PhD[1], of Queen Mary University of London, and colleagues concluded in an article published online in Annals of Oncology[2].
Jack Cuzick, PhD, FMedSci, FRCP(hon) Director, Wolfson Institute of Preventive Medicine and Head, Centre for Cancer Prevention
“It has long been known that aspirin — one of the cheapest and most common drugs on the market — can protect against certain types of cancer, but until our study, where we analysed all the available evidence, it was unclear whether the pros of taking aspirin outweighed the cons,” Cuzick said in a statement.
“Whilst there are some serious side effects that can’t be ignored, taking aspirin daily looks to be the most important thing we can do to reduce cancer after stopping smoking and reducing obesity, and will probably be much easier to implement.”
The most prominent harms of regular aspirin use relate to bleeding, which is associated with several recognized risk factors, he added. As a result, “it would be advisable to consult with a doctor before embarking on daily medication.”
Multiple cohort, case control, and randomized studies have shown that regular aspirin use can reduce the risk of cardiovascular events by 12% in the general population and in high-risk subgroups. A favorable effect on cardiovascular mortality has been more difficult to demonstrate, given the emergence of effective therapies for high-risk patients. More recently, convincing evidence has accumulated to support chemopreventive effects of aspirin on various types of cancer, particularly colon cancer, the authors noted.
Aspirin use also confers a recognized risk of bleeding, which increases with age. Obtaining optimal effects of aspirin requires a balance between risks and benefits, Cuzick and colleagues stated.
In general, previous studies focused on aspirin’s effect on specific outcomes, such as cancer or MI. Organizations that recommend risk-reducing therapies, such as the U.S. Preventive Services Task Force[3], have not investigated the sum total of risks and benefits for all major diseases.
An earlier study[4] by Cuzick and colleagues showed strong evidence that regular aspirin use afforded protection against colorectal and other types of cancer. However, they concluded that recommending routine use in the general population would be premature at that point.
The investigators revisited the aspirin issue and added new data to the information they had already reviewed. The updated analysis included case-control and cohort studies, as well as randomized trials. They investigated the effects of aspirin on colorectal, esophageal, stomach, pancreatic, lung, prostate, and breast cancer. They also examined aspirin’s effects on the risk of MI and stroke, and they calculated the risk of gastrointestinal bleeding, peptic ulcer, and major extracranial bleeding.
The largest and most consistent benefits were seen in colorectal cancer. The authors reported risk-ratio best estimates for incidence and mortality for the following cancers:
Colorectal: 0.65 (incidence), 0.60 (mortality)
Esophageal: 0.70, 0.50
Gastric: 0.70, 0.65
Lung: 0.95, 0.85
Prostate: 0.90, 0.85
Breast: 0.90, 0.95
The best estimates for MI were 0.82 for incidence and 0.95 for mortality, and for stroke the estimates were 0.95 and 1.21.
The estimated risk of major extracranial bleeding was 1.54 for regular aspirin use. Estimated mortality of gastrointestinal bleeding and peptic ulcer were 1.60 for both outcomes.
Overall, the authors found 10 years of regular aspirin use associated with a 7% reduction in the relative risk of cancer, MI, and stroke among women after 15 years and a 9% reduction in the risk of all events among men. The 20-year mortality benefit was 4%.
In general, clinicians and researchers contacted by MedPage Today gave the study favorable reviews, but none said they were ready to start routine prescribing for average-risk patients.
“What’s clear from this compilation of studies … is there is a very consistent finding, that regular use of aspirin over a period of years will reduce the risk of various types of cancer, including colorectal cancer, perhaps the most prominent to benefit,” said Neal Meropol, MD[5], of University Hospitals Case Medical Center in Cleveland.
Less clear is the risk associated with regular aspirin use across different types of patients, he added.
The study is a “fascinating” summary of the available data, said Marc Itskowitz, MD[6], of Allegheny Health Network in Pittsburgh.
“For a high-risk population for bowel and colon cancer, I would strongly consider using aspirin,” Itskowitz said. “However, in general I don’t recommend aspirin for primary prevention. … because we’re concerned that routine use of aspirin might cause gastrointestinal problems, including GI bleeding and maybe even intracranial bleeding.”
Estimates of benefits and harms of prophylactic use of aspirin in the general population
J. Cuzick
Abstract
Background Accumulating evidence supports an effect of aspirin in reducing overall cancer incidence and mortality in the general population. We reviewed current data and assessed the benefits and harms of prophylactic use of aspirin in the general population.
Methods The effect of aspirin for site-specific cancer incidence and mortality, cardiovascular events was collated from the most recent systematic reviews. Studies identified through systematic Medline search provided data regarding harmful effects of aspirin and baseline rates of harms like gastrointestinal bleeding and peptic ulcer.
Results The effects of aspirin on cancer are not apparent until at least 3 years after the start of use, and some benefits are sustained for several years after cessation in long-term users. No differences between low and standard doses of aspirin are observed, but there were no direct comparisons. Higher doses do not appear to confer additional benefit but increase toxicities. Excess bleeding is the most important harm associated with aspirin use, and its risk and fatality rate increases with age. For average-risk individuals aged 50–65 years taking aspirin for 10 years, there would be a relative reduction of between 7% (women) and 9% (men) in the number of cancer, myocardial infarction or stroke events over a 15-year period and an overall 4% relative reduction in all deaths over a 20-year period.
Conclusions Prophylactic aspirin use for a minimum of 5 years at doses between 75 and 325 mg/day appears to have favourable benefit–harm profile; longer use is likely to have greater benefits. Further research is needed to determine the optimum dose and duration of use, to identify individuals at increased risk of bleeding, and to test effectiveness of Helicobacter pylori screening–eradication before starting aspirin prophylaxis.