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Long-term daily aspirin use linked to higher than expected risk of bleeding in over-75 year-olds

Roughly 40-to-60 per cent of adults aged 75 or older in the US or Europe take daily aspirin or other antiplatelet drugs to prevent heart attacks or strokes. Life-long treatment with antiplatelet drugs is recommended for patients who have previously had a heart attack or stroke.

The advice for life-long treatment is based on trials mostly done in patients younger than 75, with a follow-up of approximately two-to-four years. Previous studies have shown there is a causal link between antiplatelet treatment and upper gastrointestinal bleeding, and although the risk is known to increase with age, estimates on the size of the risk vary widely and there is little data on whether severity of bleeding also increases with age.

Prof Peter Rothwell, lead author from the University of Oxford, UK, 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. 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 PPI is not co-prescribed. However, suddenly stopping medication is definitely not advised, so patients should always talk to their doctors.”

The Oxford Vascular Study followed 3,166 patients who had previously had a stroke or heart attack and were prescribed antiplatelet drugs (mostly aspirin). Half the patients were aged 75 or over at the start of the study. Over 10 years of the study, a total of 314 patients were admitted to hospital for bleeding. The risk of bleeding, in particular the risk of fatal or disabling bleeding, increased with age.

 For patients under 65 taking daily aspirin, the annual rate of bleeds requiring hospital admission was approximately 1.5 per cent. For patients aged 75-to-84, the annual rate rose to approximately 3.5 per cent and to 5 per cent for patients aged over 85.

 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 per cent. For patients aged 75-to-84, the rate rose to approximately 1.5 per cent, and to nearly 2.5 per cent for patients aged 85 or over.

 The outcome of non-fatal bleeds was also worse at older ages. The proportion of survivors for whom a bleed resulted in a new or sustained increase in disability rose from 3 per cent (4/157) for people aged under 75, to 25 per cent (46/183) 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 the risk of heart attacks and strokes also increases with age, the authors conclude that for patients aged 75 or older, major upper gastrointestinal bleeding as a result of antiplatelet therapy was at least as likely to be disabling or fatal as recurrent ischaemic stroke, if a PPI is not co-prescribed.

PPIs could reduce upper gastrointestinal bleeding by 70-to-90 per cent in patients receiving long-term antiplatelet treatment. However, prescription is not routine and only about a third of patients in the study were taking them. While there are some known risks associated with long-term PPI use, the authors conclude that the benefits of PPI use at older ages outweigh the risks, and guidelines should recommend the co-prescription of PPIs in this age group.

Prof Rothwell 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 research was an observational study, rather than a randomised trial, therefore it was not possible for it to show that the increased risk is entirely caused by aspirin. However, previous randomised trials have shown that at least half of bleeds occurring on aspirin are due to the medication. The authors note 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. Additionally, the findings did not take into account the potential impact of any adverse effects linked to long-term PPI use.

Writing in a linked Comment, Prof Hans-Christoph Diener, University Duisburg-Essen, Germany, said: “…The first consequence of [this] study is that the benefit-risk association in long-term antiplatelet therapy should be evaluated every three-to-five years in patients older than 75 years… The second consequence of [the] study is its support for the need to use PPIs in patients on antiplatelet therapy aged 75 years or older or in patients with a history of gastrointestinal bleeds. PPIs are under-used in patients on antiplatelet therapy, perhaps because the consequences of upper gastrointestinal bleeds were underestimated in elderly patients who were treated with aspirin.”

RCSI study identifies an effective rule for melanoma diagnosis in primary care

 study by the RCSI Department of General Practice and the HRB (Health Research Board) Centre for Primary Care Research has identified the most effective clinical prediction rules (CPRs) that aim to assist health professionals in the diagnosis of malignant melanoma. This study has been published in the BMJ Open.

This systematic review of 24 unique CPRs (identified from 51 individual studies), used to assist in distinguishing malignant melanoma from benign pigmented skin lesions, aimed to quantify the diagnostic accuracy of CPRs in primary care and specialist outpatient settings.

CPRs may be for use in clinical (ie, naked eye) examinations, or in conjunction with dermoscopy. The research showed that the ‘ABCD’ rule for dermoscopy was the best-performing CPR in a primary care setting to assist GPs in differentiating patients with clinically-significant lesions requiring referral to specialist care from those who can be treated and monitored in primary care. The ABCD rule reaches 85 per cent sensitivity and 72 per cent specificity, which is reasonably effective at ruling out melanoma. This CPR involves a GP checking a pigmented skin lesion for Asymmetry, irregular Borders, more than one or an uneven distribution of Colour, or a large (greater than 6mm) Diameter.

Melanoma is the most serious form of skin cancer and one of the most common cancers in Ireland. Its incidence is increasing rapidly amongst the Irish population, with 984 cases diagnosed in 2013 alone.

The methodology of the study involved a literature search on a range of scientific databases, including PubMed, EMBASE, SCOPUS, PROSPERO and the Cochrane Library.

Speaking on the findings from the systematic review, Prof Tom Fahey, Principal Investigator of the study and Professor and Head of the Department of General Practice at the RCSI, said: “Early detection of malignant melanoma improves prognosis for patients. As the rates of melanoma rise internationally, GPs are increasingly required to assess pigmented skin lesions. Differentiating between a benign and malignant lesion can be a difficult task, particularly at an early stage of presentation in primary care settings. Being able to categorise patients with a skin lesion into the probability of having melanoma is helpful in ensuring only those patients who require further investigation and specialist care receive it. The results of our research show that using CPRs such as the ABCD rule enhances diagnostic accuracy and improves appropriate referral to specialist dermatology care.”

The article is available online at http://dx.doi.org/10.1136/bmjopen-2016-014096.

 

Trinity Academic Gastroenterology Group experts host ‘Supper Club’

he Trinity Academic Gastroenterology Group (TAGG) recently held a gastrointestinal (GI) knowledge-sharing event for specialists in the field. The ‘Supper Club’ event took place at the RCPI in Dublin and included international expert Prof Alex Ford from St James’s University Hospital, Leeds, UK, as guest speaker.

Attended by approximately 50 healthcare professionals from across the country, the event aimed to advance GI expertise in Ireland through discussions on best practice, as well as latest scientific developments. It was organised by TAGG, an active research and clinical team working collaboratively at Tallaght Hospital, Dublin, St James’s Hospital, Dublin, Naas General Hospital and Trinity College Dublin.

The event was sponsored by healthcare company MSD.

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Pictured at the ‘Supper Club’ event L to R: Associate Professor Barry McMahon, co-founder of TAGG and Medical Physicist, Tallaght Hospital, Dublin; Associate Professor Deirdre McNamara, Director, TAGG Research Centre, Trinity College Dublin and Tallaght Hospital; Prof Alex Ford, Honorary Consultant, St James’s University Hospital, Leeds, UK; and Dr Sean Ennis, Lecturer, UCD School of Medicine Health Science Centre and founder of Genomics Medicine Ireland 

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