Abstract
SummaryBackgroundLifelong antiplatelet treatment is recommended after ischaemic vascular events, on the basis of trials done mainly in patients younger than 75 years. Upper gastrointestinal bleeding is a serious complication, but had low case fatality in trials of aspirin and is not generally thought to cause long-term disability. Consequently, although co-prescription of proton-pump inhibitors (PPIs) reduces upper gastrointestinal bleeds by 70–90%, uptake is low and guidelines are conflicting. We aimed to assess the risk, time course, and outcomes of bleeding on antiplatelet treatment for secondary prevention in patients of all ages.MethodsWe did a prospective population-based cohort study in patients with a first transient ischaemic attack, ischaemic stroke, or myocardial infarction treated with antiplatelet drugs (mainly aspirin based, without routine PPI use) after the event in the Oxford Vascular Study from 2002 to 2012, with follow-up until 2013. We determined type, severity, outcome (disability or death), and time course of bleeding requiring medical attention by face-to-face follow-up for 10 years. We estimated age-specific numbers needed to treat (NNT) to prevent upper gastrointestinal bleeding with routine PPI co-prescription on the basis of Kaplan–Meier risk estimates and relative risk reduction estimates from previous trials.Findings3166 patients (1582 [50%] aged ≥75 years) had 405 first bleeding events (n=218 gastrointestinal, n=45 intracranial, and n=142 other) during 13 509 patient-years of follow-up. Of the 314 patients (78%) with bleeds admitted to hospital, 117 (37%) were missed by administrative coding. Risk of non-major bleeding was unrelated to age, but major bleeding increased steeply with age (≥75 years hazard ratio [HR] 3·10, 95% CI 2·27–4·24; p<0·0001), particularly for fatal bleeds (5·53, 2·65–11·54; p<0·0001), and was sustained during long-term follow-up. The same was true of major upper gastrointestinal bleeds (≥75 years HR 4·13, 2·60–6·57; p<0·0001), particularly if disabling or fatal (10·26, 4·37–24·13; p<0·0001). At age 75 years or older, major upper gastrointestinal bleeds were mostly disabling or fatal (45 [62%] of 73 patients vs 101 [47%] of 213 patients with recurrent ischaemic stroke), and outnumbered disabling or fatal intracerebral haemorrhage (n=45 vs n=18), with an absolute risk of 9·15 (95% CI 6·67–12·24) per 1000 patient-years. The estimated NNT for routine PPI use to prevent one disabling or fatal upper gastrointestinal bleed over 5 years fell from 338 for individuals younger than 65 years, to 25 for individuals aged 85 years or older.InterpretationIn patients receiving aspirin-based antiplatelet treatment without routine PPI use, the long-term risk of major bleeding is higher and more sustained in older patients in practice than in the younger patients in previous trials, with a substantial risk of disabling or fatal upper gastrointestinal bleeding. Given that half of the major bleeds in patients aged 75 years or older were upper gastrointestinal, the estimated NNT for routine PPI use to prevent such bleeds is low, and co-prescription should be encouraged.FundingWellcome Trust, Wolfson Foundation, British Heart Foundation, Dunhill Medical Trust, National Institute of Health Research (NIHR), and the NIHR Oxford Biomedical Research Centre.
Highlights
Antiplatelet drugs increase the risk of major bleeding, upper gastrointestinal bleeds,[5] but this risk is reduced by 70–90% by proton-pump inhibitors (PPIs; trials are summarised in the appendix [p 2]).[6]
Clinical guidelines on secondary prevention of vascular events make no recommendations on PPI use[3,4] and, some consensus statements advocate use of these drugs in high-risk patients,[12] www.thelancet.com Vol 390 July 29, 2017
Evidence before this study Lifelong antiplatelet treatment is recommended after ischaemic vascular events on the basis of trials done at younger ages
Summary
40–66% of adults aged 75 years or older in the USA and Europe take daily aspirin or other antiplatelet drugs,[1,2] about half for secondary prevention of vascular disease, consistent with guideline recommendations for lifelong treatment.[3,4] Antiplatelet drugs increase the risk of major bleeding, upper gastrointestinal bleeds,[5] but this risk is reduced by 70–90% by proton-pump inhibitors (PPIs; trials are summarised in the appendix [p 2]).[6] coprescription of PPIs is not routine because of concerns about adverse effects,[7,8,9,10] and perhaps because upper gastrointestinal bleeds had a low case fatality in trials of aspirin[11] and are not generally thought to cause permanent disability. The risk of upper gastrointestinal bleeding on antiplatelet treatment increases with age, it is uncertain whether older age alone is a sufficient indicator of high risk and routine co-prescription of PPIs
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