While the threat of GI bleeding from aspirin is real, the bleeds are rarely fatal
The increased rate of upper gastrointestinal bleeding from aspirin when used as prevention for heart disease and cancer may have been overemphasised, researchers argue.
While concerns about gastrointestinal bleeding have been a major barrier to the widespread use of aspirin for disease prevention, cost-benefit analyses have seldom acknowledged that bleeding was very unlikely to be fatal, the authors of a meta-analysis said.
In their study of 11 trials, the researchers found no evidence that aspirin increased the frequency of fatal GI bleeds.
To the contrary, the risk of death from a bleed was lower in patients taking aspirin, with 3.7 deaths per 10,000 in people receiving aspirin compared with 4.7 per 10,000 who did not take the drug.
Major GI bleeding increased 55% in patients taking aspirin but this declined over time.
“After about three to five years of aspirin taking there appears to be no excess in GI bleeds,” the authors wrote.
Deaths from aspirin mostly occurred within the first month of treatment, which suggested that these patients had an underlying, untreated gastric pathology, they said.
“The distinction between GI bleeding and fatal bleeding is not trivial,” the authors of the article said.
Low-dose aspirin is currently recommended as an antiplatelet agent for patients with pre-existing cardiovascular disease, and has been investigated for primary prevention of CVD and primary and secondary prevention of cancer, particularly colorectal cancer.
These diseases were often disabling or terminal, whereas GI bleeding caused by aspirin was usually followed by complete recovery.
“We propose therefore that a more appropriate evaluation of the risk-benefit balance would be based on fatal adverse events, rather than on the incidence of bleeding,” the authors said.
However, Dr Mark Nelson, professor and chair of general practice at the University of Tasmania, said the findings might not apply to the elderly.
Studies on aspirin, including this one, tended to exclude the elderly due to comorbidities, Professor Nelson said, but older people were much more likely to die from GI bleeding than the middle-aged.
“As you get older you are physiologically compromised,” he said.
However, a large clinical trial is currently looking at this question. The ASPREE study is a randomised, double-blind placebo-controlled trial involving 19,000 healthy individuals, aged 70 and older.
Participants in Australia and the US will be randomly assigned 100mg aspirin or placebo for an average of five years.
The primary endpoint of the study is a composite of all-cause mortality, incident dementia and persistent physical disability. Secondary outcomes include cardiovascular events, cancer, dementia, mild cognitive impairment, physical disability, depression and major haemorrhagic events.
“We have to await the results of ASPREE study to ascertain the true adverse bleeding risk and fatality rate [of aspirin],” said Professor Nelson.
While the ASPREE study is examining primary prevention in healthy adults, high-risk groups may not receive the same benefit from taking aspirin. According to the Heart Foundation, aspirin results in a non-significant 8% to 12% reduction in risk of major cardiovascular events in people with diabetes.
Thus, the Heart Foundation’s current guidelines recommended a conservative approach to the use of aspirin therapy in prevention of CVD in people with diabetes, he said.
“[People with diabetes] are very likely to be on other disease modifying drugs, such as blood pressure and cholesterol-lowering drugs, and therefore that leaves less effect to be demonstrated by the addition of using aspirin,” Professor Nelson said.
Aspirin also increases the risk of cerebral bleeds, which have a 30% to 50% mortality rate.
However, cerebral bleeds are rare, only affecting one or two patients per year for every 10,000 people on aspirin, the study authors said.
PLOS ONE 2016, online November
