Title: Understanding hypotensive burden: use & safety of medications with blood pressure lowering effects in older people
Funder: Dunhill Medical Trust

Abstract: Background: Polypharmacy is rising: 44–57% of older adults are on ≥5 drugs and approximately 10% on ≥10 drugs [1,2]. Prescribing is predominantly carried out in primary care, where 90% of all NHS contact takes place [3]. Problematic polypharmacy resulting in harmful drug interactions and adverse drug reactions (ADRs) is most prevalent in older people [4]; 35% of community-dwelling older adults experience an ADR annually [5] implicated in 6.5% of admissions [6]. More than 50 commonly prescribed drugs cite “hypotension” as an adverse effect [7] including: anti-depressants (prevalent in 11% of older people, rising, with mixed evidence on benefit) [2,8], analgesics (prevalent in 21% aged 75+) [2], and newer drugs such as Direct-Acting Oral Anticoagulants [9]. These medications have the potential to cause postural hypotension [10-12]; affecting 20-65% of older people and an independent cause of falls [12,13]. Many studies have explored the relationship between antihypertensives, postural hypotension and falls [14] but few investigate drugs with hypotension as an unintended side-effect. As clinical trials advocate tighter hypertension targets in older people [15], understanding safety of drugs with hypotensive properties is important to optimise medications, so maximum benefit is gained with least harm. One study found hypotension was the second commonest ADR overall and the second commonest classed as a “Serious Harm” causing hospitalisation, permanent harm or death [16]. Concomitant use of medications with hypotensive potential has a cumulative effect [11] and withdrawal of certain drugs can reduce falls [17]. To date, no studies explore drug combinations or describe hypotensive burden. Anticholinergic burden is far better understood [18]. Standard animal toxicity studies for drug-related hypotension do not extrapolate ADRs to practice, highlighting the value of epidemiological evidence [19]. Hypotheses: 1) Drugs with hypotensive effects are commonly prescribed and most prevalent in those with higher overall prescriptions (advancing age, females)[4]. 2) Particular combinations of drugs may be associated with increased postural hypotension, adverse BP lowering and falls in older people, particularly sub-groups at higher risk at baseline: dementia [20], Parkinson’s, recurrent fallers, frailty [20-22]. Aim: To examine cumulative risk of medications with hypotensive side-effects and characterise “hypotensive burden” in older people with polypharmacy (≥5 drugs) [23] Methods: Cohort study using The Health Improvement Network (THIN) including >900,000 older people [24] and the Delirium and Population Health Informatics Cohort (DELPHIC) [25]. Potential impact: Support safer prescribing and appropriate polypharmacy in older people and inform development of a Hypotensive Burden Scale to guide clinical practice.

Lay abstract: “We dislike polypharmacy as much as it is possible, and we would never exhibit a remedy of any kind unless we had a scientific reason for so doing and unless we were prepared to defend our method of treatment”. W Newnham, Provincial Medical and Surgical Journal, 1848. These days many healthy older people aged over 65 take at least 5 medications a day, and those with many illnesses are likely to take even more. This is because over the years, we have made enormous strides in the prevention and treatment of common medical conditions such as heart attacks and depression. But better treatment can also come with its problems, as the numbers of pills we take rise and rise. All pills have side effects and we do not know enough about how different medications interact with each other. We need to know more about the safety of taking many different pills, particularly for older frailer people who are living longer. One worrying side effect of many medications prescribed today is the lowering of blood pressure. We know that an older person with low blood pressure is more likely to fall. Falls can lead to breaking bones, being admitted to hospital, loss of physical and social confidence, poorer quality of life and even premature deaths. Falls are very common amongst older people in the United Kingdom, about a third fall each year. Since these medications can increase the likelihood of falling (especially when taking more than one with this side effect), we want to investigate how they may interact to cause harm in older people. This project could help prevent falls. It could help doctors, nurses and pharmacists to make better choices and reduce the numbers of pills older people are taking. So they can stay well for longer, getting the most from their medication without any harm. Cutting down the numbers of unnecessary pills older people are taking could improve wellbeing and quality of life. It could also reduce costs for the NHS. Medications cost the NHS around £8.3 billion a year. These savings could be ploughed back into developing and improving other services for older people. This project could also pave a way for much more research looking into other types of medications and will encourage safer ways of prescribing medication for older people in future.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CARDIOVASCULAR