Publishing in The Lancet researchers report that long-term daily aspirin use is linked to a higher than expected risk of bleeding in adults aged 75 or over. The scientists claim that proton-pump inhibitors should be co-prescribed in this age group to reduce the risk of bleeds.
These comments accompanied a briefing.
Prof. Alan Boyd, President, Faculty of Pharmaceutical Medicine, said:
“Taking an aspirin a day after people have suffered from a heart attack or a stroke to prevent further problems is recommended for patients and has clear benefits. Also it is known that long term use of aspirin and other antiplatelet drugs does cause some bleeding problems, but it has been considered that the benefits of treating patients with aspirin after a heart attack or stroke outweighed the risks of bleeding in all patients. For patients younger than 75, this is still the case. However, this paper provides evidence that for patients aged 75 years and over, the risks of having a major bleed particularly from ulcers in the gastrointestinal tract are significant and for some older patients the risk of bleeds may be larger than the benefit of preventing a further heart attack. However, there is a way of still having the benefit of the aspirin while significantly minimising the risk. As described in the paper, there is fortunately a treatment available that can be given along with the aspirin to reduce the risk of bleeding, and these are medicines known as proton-pump-inhibitors (PPI) which help prevent the ulcers occurring which cause the bleeding.
“This is an important finding for two reasons; first it has highlighted a serious problem that does occur in the over-75 population treated with long-term aspirin that needs to be recognised; and secondly it provides a solution to the problem in the recommendation of taking a PPI medicine along with the aspirin to prevent the bleeding.
“Also when major bleeding does occur in this older patient group it is more likely to be severe leading to increased hospitalisation and can be fatal. There are therefore economic factors that need to be considered as well, since treating patients with a major bleed incurs a significant cost to the Health Service, whilst treating a patient with aspirin and a PPI is very small in comparison.
“This study was a prospective study involving just under 3200 patients, that were recruited over a 10 year period, who had suffered a first heart attack or stroke and who were subsequently treated with aspirin or other antiplatelet drugs to prevent similar events occurring. The main focus of the study was to determine how many patients were admitted to hospital for bleeding. The results were then compared for bleeding events for patients under the age of 75 years with those over 75. The study appears to have been well conducted and involved an appropriate number of patients to allow the study conclusions to be made.
“It is now important that the combined use of aspirin and other antiplatelet drugs with a PPI is now included in the appropriate treatment guidelines for patients over 75 years who have had a stroke or heart attack.”
Dr Amitava Banerjee, Senior Clinical Lecturer in Clinical Data Science and Honorary Consultant Cardiologist, UCL, said:
“This is a high quality analysis within the well-established Oxford Vascular Study. Aspirin is proven to significantly reduce risk of heart attacks and strokes, particularly in people who have already had these conditions (‘secondary prevention’). However, aspirin does carry a bleeding risk, particularly gastrointestinal bleeding. The authors here answer two questions. First, how much more risk is there of bleeding with aspirin in older individuals (≥75 years)? Second, what is the impact of proton pump inhibitors (PPIs), such as omeprazole, on the risk of bleeding in these older individuals? The analyses used hazard ratios which give an instantaneous risk at a specific time (in this case at the time of the bleeding event), whereas relative risks or odds ratios give an estimate of risk over a whole study period. The study looked at patients who had previously had a transient ischaemic attack (‘mini-stroke’), stroke or heart attack.
“Major bleeding (requiring medical attention) was 3 times more likely and fatal bleeding was 5 times more likely in older people, compared with those individuals less than 75 years old. Importantly, gastrointestinal bleeding accounted for half of the major bleeds in older people and were significantly more common than intra-cerebral bleeding. The authors estimate that routine use of proton pump inhibitors (PPI) in individuals aged 85 years or older could prevent one disabling or fatal upper gastrointestinal bleed over 5 years if 25 people are treated with them. By comparison, we would need to treat 338 individuals younger than 65 years to achieve the same effect, because bleeding was much less common in these younger people so the risk is much lower.
“In older individuals (over 75 years old), where aspirin is necessary there is a strong argument for clinicians to prescribe a proton pump inhibitor as well. The study highlights that both patients and health professionals must weigh up the risks and the benefits of all drugs, including aspirin, and this should be revisited every 3-5 years, if not more. Trial data do not provide all the relevant information to the individual patient, whether in terms of age or full range of risk and benefit – previous trials looking at aspirin have not included many people over the age of 75. Observational data, such as this study, can help address these questions and observe the older age-groups that had been missed by the trials. Therefore, a combination of observational data and trial data have to be used in more sophisticated ways to make informed decisions for individual patients.”
Prof. Tony Fox, Pharmaceutical Medicine Group, King’s College London, said:
“This study has a prospective, long-term cohort design, which is among the most rigorous types of pharmacoepidemiological research. Because the results have been presented as hazard ratios (which are difficult to interpret) rather than absolute values, we need to be careful not to over-interpret the size of the problem – it would not be correct, for example, to say that the risk of a serious bleed is ten times higher in the over-75s than in younger people. However, it is clear from the data presented that in the over-75s, taking proton pump inhibitors (PPI) along with aspirin was associated with a reduced likelihood of bleeding. If elderly patients need to be prescribed aspirin, for example after having a heart attack or stroke, then doctors should also think about prescribing proton pump inhibitors along with the aspirin (paying close attention to the patient’s tolerability of both drugs) in order to reduce the probability of bleeding in this age group.”
Dr Tim Chico, Reader in Cardiovascular Medicine / consultant cardiologist, University of Sheffield, said:
“This is a well conducted study that follows a group of patients who were prescribed aspirin or other blood thinning medication after a heart attack or stroke to monitor how frequently they suffered bleeding. Although bleeding is a well-recognised side effect of aspirin, this drug is still seen by many people as harmless, perhaps because of how easily it can be bought over the counter. In this group of patients taking aspirin, as expected there were a number of patients who suffered bleeds, and the rate of this increased with age; over the age of 85, 1 in 20 people in this study suffered a bleed over 10 years. Some of these bleeds were disabling or even fatal, so it is important to try to find ways to reduce this bleeding risk.
“Prescription of any drug is a balance between the benefits of the medication against its risks, and aspirin is no different. Certainly, people should not stop their aspirin if it has been prescribed by a doctor after a stroke or heart attack, since stopping it can cause another heart attack or stroke. However, I would strongly recommend that people who are considering taking aspirin to prevent potential future problems such as cancer or heart attack (i.e. not for secondary prevention) should discuss this with their doctor.
“It is important to review the need for all prescribed medications from time to time, and if someone is taking aspirin it is possible that acid-suppressing tablets called PPIs might reduce the risk of bleeding, as the authors of this study suggest.”
* ‘Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular events: a population-based cohort study’ by Linxin Li et al. published in The Lancet on Tuesday 13 June 2017.
Dr Amitava Banerjee: “Dr Banerjee completed his DPhil under the supervision of Professor Peter Rothwell but had no involvement in the current study.”
Prof. Tony Fox: “No interests to declare.”
Dr Tim Chico: “I am a committee member and Treasurer of the British Atherosclerosis Society, a charity established in 1999 to promote UK atherosclerosis research.”