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Proton pump inhibitors

Aspirin and PPIs should be co-prescribed in older patients because of bleeding risk, say researchers

Patients aged over 75 years who take aspirin-based antiplatelet therapy should be co-prescribed proton-pump inhibitors (PPIs) because of a previously under-recognised risk of serious and disabling upper gastrointestinal bleeding, say the authors of a Lancet study[1].

The research involved 3,166 patients, half of whom were aged 75 years and over, who took part in a 10-year prospective study that followed up patients with a first myocardial infarction, transient ischemic attack or stroke. The participants were treated with predominantly aspirin-based antiplatelet drugs without routine gastroprotection.

The researchers found that while the risk of non-major bleeding was unrelated to age, the risk of major bleeds, and particularly fatal bleeds, increased steeply with age. Compared with those under 75 years, older participants had a 2.6-fold increased risk of major non-fatal bleeding and a 5.5-fold increased risk of fatal bleeding.

They also found a four-fold increased risk of major gastrointestinal bleeds in older patients and that the majority of major gastrointestinal bleeds in those aged over 75 years were disabling or fatal (45 [62%) of 73). The team says that this finding goes contrary to conventional wisdom that most upper gastrointestinal bleeds are not serious in nature.

PPIs are not widely prescribed for prevention of gastrointestinal bleeds in patients taking antiplatelet therapy, which the researchers say is probably because of concerns about adverse effects and the perception that upper gastrointestinal bleeds aren’t generally serious.

“Previous studies have shown there is a clear benefit of short-term antiplatelet treatment following a heart attack or stroke,” says lead author Peter Rothwell from the University of Oxford. “But our findings raise questions about the balance of risk and benefit of long-term daily aspirin use in people aged 75 years or over if a proton-pump inhibitor is not co-prescribed.”

Based on their findings, they say that co-prescription of PPIs should be encouraged for all patients aged over 75 years receiving aspirin-based antiplatelet therapy and considered for routine recommendation in future secondary prevention guidelines.

Professor Helen Stokes-Lampard, chair of the Royal College of General Practitioners, says: “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 proton pump inhibitor as a secondary drug — but this does raise a number of health implications. It will continue to be necessary to make decisions on a case-by-case basis, considering the patient’s unique circumstances and medical history, as well as the medications they are already taking and how these will interact with each other.”

Citation: The Pharmaceutical Journal DOI: 10.1211/PJ.2017.20202958

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