Abstract Objective To examine the association between antihypertensive treatment and specific adverse events. Design Systematic review and meta-analysis. Eligibility criteria Randomised controlled trials of adults receiving antihypertensives compared with placebo or no treatment, more antihypertensive drugs compared with fewer antihypertensive drugs, or higher blood pressure targets compared with lower targets. To avoid small early phase trials, studies were required to have at least 650 patient years of follow-up. Information sources Searches were conducted in Embase, Medline, CENTRAL, and the Science Citation Index databases from inception until 14 April 2020. Main outcome measures The primary outcome was falls during trial follow-up. Secondary outcomes were acute kidney injury, fractures, gout, hyperkalaemia, hypokalaemia, hypotension, and syncope. Additional outcomes related to death and major cardiovascular events were extracted. Risk of bias was assessed using the Cochrane risk of bias tool, and random effects meta-analysis was used to pool rate ratios, odds ratios, and hazard ratios across studies, allowing for between study heterogeneity (τ 2 ). Results Of 15 023 articles screened for inclusion, 58 randomised controlled trials were identified, including 280 638 participants followed up for a median of 3 (interquartile range 2-4) years. Most of the trials (n=40, 69%) had a low risk of bias. Among seven trials reporting data for falls, no evidence was found of an association with antihypertensive treatment (summary risk ratio 1.05, 95% confidence interval 0.89 to 1.24, τ 2 =0.009). Antihypertensives were associated with an increased risk of acute kidney injury (1.18, 95% confidence interval 1.01 to 1.39, τ 2 =0.037, n=15), hyperkalaemia (1.89, 1.56 to 2.30, τ 2 =0.122, n=26), hypotension (1.97, 1.67 to 2.32, τ 2 =0.132, n=35), and syncope (1.28, 1.03 to 1.59, τ 2 =0.050, n=16). The heterogeneity between studies assessing acute kidney injury and hyperkalaemia events was reduced when focusing on drugs that affect the renin angiotensin-aldosterone system. Results were robust to sensitivity analyses focusing on adverse events leading to withdrawal from each trial. Antihypertensive treatment was associated with a reduced risk of all cause mortality, cardiovascular death, and stroke, but not of myocardial infarction. Conclusions This meta-analysis found no evidence to suggest that antihypertensive treatment is associated with falls but found evidence of an association with mild (hyperkalaemia, hypotension) and severe adverse events (acute kidney injury, syncope). These data could be used to inform shared decision making between doctors and patients about initiation and continuation of antihypertensive treatment, especially in patients at high risk of harm because of previous adverse events or poor renal function. Registration PROSPERO CRD42018116860.
Background The burden of hypertension in primary care is high, and alternative models of care, such as pharmacist management, have shown promise. However, data describing outcomes from routine consultations between pharmacists and patients with hypertension are lacking. Aim To identify factors associated with referral of patients from pharmacies to general practice within the first 2 weeks of starting a new antihypertensive medication. Design and setting Multivariate logistic regression conducted on data from community pharmacies in England. Method Data were obtained from the New Medicine Service between 2011 and 2012. Analyses were conducted on 131 419 patients. In all, 15 predictors were included in the model, grouped into three categories: patient-reported factors, demographic factors, and medication-related factors. Results Mean patient age was 65 years (±13 years), and 85% of patients were of white ethnicity. A total of 5895 (4.5%) patients were referred by a pharmacist to a GP within the first 2 weeks of starting a new antihypertensive medication. Patients reporting side effects (adjusted odds ratio [OR] 11.60, 95% confidence interval [CI] = 10.85 to 12.41) were most likely to be referred. Prescriptions for alpha-blockers were associated with referral (adjusted OR 1.28, 95% CI = 1.12 to 1.47), whereas patients receiving angiotensin-II receptor blockers were less likely to be referred (adjusted OR 0.89, 95% CI = 0.80 to 0.99). Conclusion Most patients were followed up by pharmacists without the need for referral. Patient-reported side effects, medication-related concerns, and the medication class prescribed influenced referral. These data are reassuring, in that additional pharmacist involvement does not increase medical workload appreciably, and support further development of pharmacist-led hypertension interventions.
Background: Smoking is attributed to both micro- and macrovascular complications at any stage of metabolic deregulation including prediabetes, particularly those who develop the disease at a young age. Current global diabetes prevention programmes appear to be glucocentric, and do not fully acknowledge the ramifications of cardiorenal risk factors in smokers. A more holistic approach is needed to prevent vascular complications in people with prediabetes and diabetes. Considering albuminuria as a surrogate marker for both micro- and macrovascular complications, we investigated the relationship between smoking status and albuminuria in people with prediabetes and diabetes, and explored how this relationship is affected by age, antihypertensive, and cholesterol-lowering medications.Methods: A logistic regression model was fitted on UK Biobank dataset with 502,490 participants. A subgroup analysis investigated the effect of age, smoking status, antihypertensive and cholesterol-lowering medications on this relationship in people with prediabetes and diabetes.Findings: Compared with non-smokers, the odds of albuminuria in smokers with prediabetes and diabetes were 1.43 (95% CI 1.16 - 1.77), and 1.29 (95% CI 1.02 – 1.64), respectively. People younger than 50 with prediabetes, and diabetes were at increased risk of albuminuria, compared with those over 50 years old, with OR 1.62 and 1.34, respectively. The odds of albuminuria remained statistically significantly high, in prediabetes and diabetes groups, despite being on anti-hypertensive, and cholesterol-lowering medications. The odds of albuminuria were not attenuated in ex-smokers either with prediabetes or diabetes.Interpretation: Smokers with prediabetes are at a higher risk of albuminuria than those with diabetes. The risk in ex-smokers did not decline to a statistically significant level, presumably due to insufficient lag period since quitting. Current strategies for cholesterol and hypertension management may not be sufficient to reduce the risk of albuminuria in people both with prediabetes and diabetes. Smoking cessation and continued abstinence in people with prediabetes and diabetes should be promoted in order to prevent future vascular complications. Screening for albuminuria should be incorporated in the NHS health check.Funding Information: No external funding was received for this study. Declaration of Interests: DK declares no duality of interest. This publication is undertaken using UK Biobank data under application no – 61894 and is a part of MD thesis. JPS receives funding from the Wellcome Trust/Royal Society via a Sir Henry Dale Fellowship (ref: 211182/Z/18/Z) and an NIHR Oxford Biomedical Research Centre (BRC) Senior Fellowship. For open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. JRA is supported by a NIHR Clinician Scientist Award (CS 2018-18-ST2-007) SdeL reports that through his university, he has had grants not directly relating to this work, from AstraZeneca, GSK, Sanofi, Seqirus, and Takeda for vaccine research and membership of advisory boards for AstraZeneca, Sanofi and Seqirus. KK is supported by the National Institute for Health Research (NIHR) Applied Research Collaboration East Midlands (ARC EM) and the NIHR Leicester Biomedical Research Centre (BRC). Prof Khunti has acted as a consultant and speaker for Amgen, AstraZeneca, Bayer, Novartis, Novo Nordisk, Roche, Sanofi-Aventis, Lilly, Servier and Merck Sharp & Dohme. He has received grants in support of investigator and investigator-initiated trials from AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Pfizer, Boehringer Ingelheim and Merck Sharp & Dohme. KK has received funds for research, honoraria for speaking at meetings and has served on advisory boards for AstraZeneca, Lilly, Sanofi-cool=Aventis, Merck Sharp & Dohme and Novo Nordisk. MJD reports personal fees from Novo Nordisk, Sanofi-Aventis, Lilly, Merch Sharp & Dohme, Boehringer Ingelheim, Astra Zeneca, Janssen, Servier, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceuticals International Inc. She has also received grants from Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim, Janssen outside the submitted work 24 KK and MJD are members of the National Institute for Health and Clinical Excellence public health guidance on preventing type 2 diabetes and both are advisers to the UK epartment of Health for the NHS health checks programme. All other authors have nothing to confirm. Ethics Approval Statement: This is a retrospective cross-sectional study using the UK Biobank (UKB) data. UK Biobank received ethics approval from the Northwest Multi-centre Research Ethics Committee (MREC). It has also received approval from the National Information Governance Board for Health & Social Care (NIGB). For this study, ethics approval was also granted by the Research Ethics Committee, Sheffield School of Health and Related Research, University of Sheffield Application No 038586, 09/03/2021).
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Background Hospital prealerting in acute stroke improves the timeliness of subsequent treatment, but little is known about the impact of prehospital assessments on in-hospital care. Objective Examine the association between prehospital assessments and notification by emergency medical service staff on the subsequent acute stroke care pathway. Methods This was a cohort study of linked patient medical records. Consenting patients with a diagnosis of stroke were recruited from two urban hospitals. Data from patient medical records were extracted and entered into a Cox regression analysis to investigate the association between time to CT request and recording of onset time, stroke recognition (using the Face Arm Speech Test (FAST)) and sending of a prealert message. Results 151 patients (aged 71±15 years) travelled to hospital via ambulance and were eligible for this analysis. Time of symptom onset was recorded in 61 (40%) cases, the FAST test was positive in 114 (75%) and a prealert message was sent in 65 (44%). Following adjustment for confounding, patients who had time of onset recorded (HR 0.73, 95% CI 0.52 to 1.03), were FAST-positive (HR 0.54, 95% CI 0.37 to 0.80) or were prealerted (HR 0.26, 95% CI 0.18 to 0.38), were more likely to receive a timely CT request in hospital. Conclusions This study highlights the importance of hospital prealerting, accurate stroke recognition, and recording of onset time. Those not recognised with stroke in a prehospital setting appear to be excluded from the possibility of rapid treatment in hospital, even before they have been seen by a specialist.
Background: The balance of benefits and risks associated with lowering blood pressure levels in individuals with dementia remains controversial with a lack of evidence for possible harms associated with antihypertensive treatment (AHT). Objectives: We examined the association between AHT and serious adverse events (SAEs) in individuals with dementia compared to those without. Methods: This was a retrospective analysis using nationally representative, UK general practice population between 1998 and 2018, using data from electronic health records (Clinical Practice Research Datalink, GOLD). Individuals included were age ≥40 years and not previously prescribed AHT. Diagnosis of dementia was based on standardised clinical codes. The primary outcome was the first hospitalisation or death from a fall within 10 years of the follow-up period. Secondary outcomes were first hospitalisation or death from hypotension, syncope, and fracture. Cox regression analyses, adjusted for propensity score were used to assess the risk of SAEs. Results: In a population of 1,219,732 individuals, 23,510 had dementia. Antihypertensive medications were newly prescribed in 4,062/23,510 (17.3%) individuals with dementia and 142,385/1,196,222 (11.9%) individuals without dementia in the 12 months exposure period. In individuals with dementia, AHTs were associated with an increased risk of hospitalisation or death from falls (adjusted hazard ratio [aHR] 1.15, 95% confidence interval [CI] 1.08, 1.22), hypotension (aHR 1.51, 95%CI 1.29, 1.78), syncope (aHR 1.34, 95%CI 1.11, 1.61), but not fracture (aHR 1.05, 95%CI 0.96, 1.15). In individuals without dementia, the association between AHT and SAEs was similar, with an increased risk of hospitalisation or death from falls (aHR 1.07, 95%CI 1.05, 1.10). However, absolute risk of falls with AHT per 10,000 individuals per year was significantly higher in individuals with dementia (47, 95%CI 26, 70) compared to those without (14, 95%CI 10, 18). The absolute risks of hypotension and syncope with AHT were also higher in the individuals with dementia compared to those without. Conclusions: AHT was associated with increased risk of SAEs in individuals with and without dementia, however, the absolute risk of harm from falls was more than double in individuals with dementia. Clinicians, patients, and their carers should consider these risks before starting new antihypertensive medications, particularly in the context of dementia, although they remain small.
The diagnosis and management of hypertension depends on accurate measurement of blood pressure (BP) in order to target antihypertensive treatment appropriately. Most BP measurements take place in a clinic setting, but it has long been recognised that readings taken out-of-office (via home or ambulatory monitoring) estimate true underlying BP more accurately. Recent studies have shown that the change in clinic BP over multiple readings is a significant predictor of the difference between clinic and out-of-office BP. Used in combination with patient characteristics, this change has been shown to accurately predict a patient's out-of-office BP level. The present study proposes to collect real-life BP data to prospectively validate this new prediction tool in routine clinical practice.A prospective, multicentre observational cohort design will be used, recruiting patients from primary and secondary care. All patients attending participating centres for ambulatory BP monitoring will be eligible to participate. Anonymised clinical data will be collected from all eligible patients, who will be invited to give informed consent to permit identifiable data to be collected for data linkage to external outcome registries. Descriptive statistics will be used to calculate the sensitivity, specificity, positive and negative predictive values of the out-of-office BP prediction tool. Area under the receiver operator characteristic curve statistics will be used to examine model performance.Ethical approval for this study has been obtained from the National Research. Ethics Service Committee South Central-Oxford A (reference; 15/SC/0184), and site-specific R&D approval has been acquired from the relevant NHS trusts. All findings will be presented at relevant conferences and published in peer-reviewed journals, on the study website and disseminated in lay and social media where appropriate.
Recent research and guidelines recommend the routine use of ambulatory blood pressure monitoring for the diagnosis of hypertension, so accuracy of such monitors is more important than ever.: To systematically review the literature regarding the accuracy of ambulatory monitors currently in use.Medline, Embase, Cinahl, the Cochrane database, Medion and the dabl Educational Trust website were searched until February 2011. No language or publication date limits were applied. Data were extracted separately by two independent reviewers. Methodological quality was assessed by whether a validation protocol had been used and followed correctly.From 5420 journal articles identified, 108 met the inclusion criteria. Excluding studies assessing monitors no longer in use, 40 relevant studies were found using 21 different monitors. Thirty-eight (95%) studies used a validation protocol of which 28 studies assessed a monitor in the general population. Of these, protocols were passed in 24 of 28 studies, but 12 of 24 (50%) found a difference of at least 5 mmHg systolic between the test device and the reference standard for 30% or more of the readings. Of the 10 studies conducted in special population groups (e.g. pregnancy, elderly people), only four devices passed the protocols. Only six (16%) studies correctly adhered to the protocols.Published validation studies assessed most ambulatory monitors as accurate, but many failed to adhere to the underlying protocols, undermining this conclusion and peer review standards. Furthermore, most monitors which 'passed' validation showed significant variation in blood pressure from the reference standard, highlighting inadequacies in older validation protocols. Future validation studies should use protocols with simpler methodologies but more rigorous accuracy criteria.
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