Long-term daily aspirin use is linked to a higher than expected risk of “disabling or fatal” bleeding in adults aged 75 or over, according to researchers in Oxford.
As a result, they suggest that proton-pump inhibitors (PPIs) should be co-prescribed with aspirin in this age group to reduce the risk of bleeds.
“Our findings raise questions about the balance of risk and benefit of long-term daily aspirin use”
Roughly 40-60% of adults aged 75 or older in Europe take daily aspirin or other antiplatelet drugs to prevent heart attacks or strokes, as it is recommended for secondary prevention.
However, the advice for lifelong treatment as secondary prevention is based on trials mostly done in patients younger than 75, with a follow up of approximately two to four years.
Meanwhile, other studies have shown a causal link between antiplatelet treatment and upper gastrointestinal bleeding, but estimates on the size of the risk vary widely.
The Oxford Vascular Study, published in The Lancet, followed 3,166 patients who had previously had a cardiovascular event and were prescribed antiplatelets – mostly aspirin.
Half were aged 75 or over at the start of the 10-year study. During the study, a total of 314 patients were admitted to hospital for bleeding, with the risk increasing with age.
For patients under 65 taking daily aspirin, the annual rate of bleeds requiring admission was around 1.5%. For patients aged 75-84, it rose to around 3.5% and to 5% for those over 85.
“It will continue to be necessary to make decisions of a case by case basis”
Similarly, the risk of disabling or fatal bleeding increased with age. For patients aged under 65, the annual rate of life-threatening or fatal bleeds was less than 0.5%. But for patients aged 75-84, the rate rose to around 1.5%, and to nearly 2.5% for patients aged 85 or over.
The outcome of non-fatal bleeds was also worse at older ages, found the study, which was partly funded by the British Heart Foundation and the National Institute of Health Research.
The proportion of survivors for whom a bleed resulted in a new, or sustained increase in disability rose from 3% for people aged under 75, to 25% for people aged over 75.
Overall, the risk of disabling or fatal bleeding over 10 years was 10 times higher at ages 75 years or older, compared to younger patients.
Although heart attack or stroke risk also increases with age, the researchers said that in the overs 75s major upper gastrointestinal bleeding caused by antiplatelet therapy was at least as likely to be disabling or fatal as recurrent stroke – if a PPI was not co-prescribed.
While there are some risks from long-term PPI use, they concluded that their benefits at older ages outweighed them and guidelines should recommend the co-prescription of PPIs.
Call to co-prescribe PPIs with daily aspirin for older patients
Lead study author Professor Peter Rothwell, from Oxford University, said: “We have known for some time that aspirin increases the risk of bleeding for elderly patients. But our new study gives us a much clearer understanding of the size of the increased risk and of the severity and consequences of bleeds.
“Previous studies have shown there is a clear benefit of short term antiplatelet treatment following a heart attack or stroke,” he said. “But our findings raise questions about the balance of risk and benefit of long-term daily aspirin use in people aged 75 or over if a proton-pump inhibitor is not co-prescribed.
He added: “While there is some evidence that long-term PPI use might have some small risks, this study shows that the risk of bleeding without them at older ages is high, and the consequences significant. In other words, these new data should provide reassurance that the benefits of PPI use at older ages will outweigh the risks.”
The authors noted that the majority of patients in the study were taking aspirin (75mg enteric coat) with only a few patients taking clopidogrel, meaning that the findings may not apply to other antiplatelet drugs.
helen stokes lampard blog image
Professor Helen Stokes-Lampard, chair of the Royal College of GPs, said: “The study does reassure us that in most cases, aspirin is still the most appropriate course of treatment for patients, but highlights the importance of managing its use carefully and effectively and that some patients may require additional medication to protect them.
“It’s helpful that the researchers suggest action to mitigate this risk – the prescription of a PPI as a secondary drug – but this does raise a number of health implications,” she said. “It will continue to be necessary to make decisions of a case by case basis.”