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OBJECTIVE: To develop and externally validate the STRAtifying Treatments In the multi-morbid Frail elderlY (STRATIFY)-Falls clinical prediction model to identify the risk of hospital admission or death from a fall in patients with an indication for antihypertensive treatment. DESIGN: Retrospective cohort study. SETTING: Primary care data from electronic health records contained within the UK Clinical Practice Research Datalink (CPRD). PARTICIPANTS: Patients aged 40 years or older with at least one blood pressure measurement between 130 mm Hg and 179 mm Hg. MAIN OUTCOME MEASURE: First serious fall, defined as hospital admission or death with a primary diagnosis of a fall within 10 years of the index date (12 months after cohort entry). Model development was conducted using a Fine-Gray approach in data from CPRD GOLD, accounting for the competing risk of death from other causes, with subsequent recalibration at one, five, and 10 years using pseudo values. External validation was conducted using data from CPRD Aurum, with performance assessed through calibration curves and the observed to expected ratio, C statistic, and D statistic, pooled across general practices, and clinical utility using decision curve analysis at thresholds around 10%. RESULTS: Analysis included 1 772 600 patients (experiencing 62 691 serious falls) from CPRD GOLD used in model development, and 3 805 366 (experiencing 206 956 serious falls) from CPRD Aurum in the external validation. The final model consisted of 24 predictors, including age, sex, ethnicity, alcohol consumption, living in an area of high social deprivation, a history of falls, multiple sclerosis, and prescriptions of antihypertensives, antidepressants, hypnotics, and anxiolytics. Upon external validation, the recalibrated model showed good discrimination, with pooled C statistics of 0.833 (95% confidence interval 0.831 to 0.835) and 0.843 (0.841 to 0.844) at five and 10 years, respectively. Original model calibration was poor on visual inspection and although this was improved with recalibration, under-prediction of risk remained (observed to expected ratio at 10 years 1.839, 95% confidence interval 1.811 to 1.865). Nevertheless, decision curve analysis suggests potential clinical utility, with net benefit larger than other strategies. CONCLUSIONS: This prediction model uses commonly recorded clinical characteristics and distinguishes well between patients at high and low risk of falls in the next 1-10 years. Although miscalibration was evident on external validation, the model still had potential clinical utility around risk thresholds of 10% and so could be useful in routine clinical practice to help identify those at high risk of falls who might benefit from closer monitoring or early intervention to prevent future falls. Further studies are needed to explore the appropriate thresholds that maximise the model's clinical utility and cost effectiveness.

BACKGROUND: Deprescribing of antihypertensive medications for older patients with normal blood pressure is recommended by some clinical guidelines, where the potential harms of treatment may outweigh the benefits. This study aimed to assess the cost-effectiveness of this approach. METHODS: A Markov patient-level simulation was undertaken to model the effect of withdrawing one antihypertensive compared with usual care, over a life-time horizon. Model population characteristics were estimated using data from the OPTiMISE antihypertensive deprescribing trial, and the effects of blood pressure changes on outcomes were derived from the literature. Health-related quality of life was modeled in Quality-Adjusted Life Years (QALYs) and presented as costs per QALY gained. RESULTS: In the base-case analysis, medication reduction resulted in lower costs than usual care (mean difference £185), but also lower QALYs (mean difference 0.062) per patient over a life-time horizon. Usual care was cost-effective at £2975 per QALY gained (more costly, but more effective). Medication reduction resulted more heart failure and stroke/TIA events but fewer adverse events. Medication reduction may be the preferred strategy at a willingness-to-pay of £20 000/QALY, where the baseline absolute risk of serious drug-related adverse events was ≥7.7% a year (compared with 1.7% in the base-case). CONCLUSIONS: Although there was uncertainty around many of the assumptions underpinning this model, these findings suggest that antihypertensive medication reduction should not be attempted in many older patients with controlled systolic blood pressure. For populations at high risk of adverse effects, deprescribing may be beneficial, but a targeted approach would be required in routine practice.

BackgroundAntihypertensives reduce the risk of cardiovascular disease but are also associated with harms including acute kidney injury (AKI). Few data exist to guide clinical decision making regarding these risks.AimTo develop a prediction model estimating the risk of AKI in people potentially indicated for antihypertensive treatment.Design and settingObservational cohort study using routine primary care data from the Clinical Practice Research Datalink (CPRD) in England.MethodPeople aged ≥40 years, with at least one blood pressure measurement between 130 mmHg and 179 mmHg were included. Outcomes were admission to hospital or death with AKI within 1, 5, and 10 years. The model was derived with data from CPRD GOLD (n= 1 772 618), using a Fine–Gray competing risks approach, with subsequent recalibration using pseudo-values. External validation used data from CPRD Aurum (n= 3 805 322).ResultsThe mean age of participants was 59.4 years and 52% were female. The final model consisted of 27 predictors and showed good discrimination at 1, 5, and 10 years (C-statistic for 10-year risk 0.821, 95% confidence interval [CI] = 0.818 to 0.823). There was some overprediction at the highest predicted probabilities (ratio of observed to expected event probability for 10-year risk 0.633, 95% CI = 0.621 to 0.645), affecting patients with the highest risk. Most patients (>95%) had a low 1- to 5-year risk of AKI, and at 10 years only 0.1% of the population had a high AKI and low CVD risk.ConclusionThis clinical prediction model enables GPs to accurately identify patients at high risk of AKI, which will aid treatment decisions. As the vast majority of patients were at low risk, such a model may provide useful reassurance that most antihypertensive treatment is safe and appropriate while flagging the few for whom this is not the case.

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.

IntroductionRecent evidence suggests that larger blood pressure reductions and multiple antihypertensive drugs may be harmful in older people, particularly frail individuals with polypharmacy and multimorbidity. However, there is a lack of evidence to support deprescribing of antihypertensives, which limits the practice of medication reduction in routine clinical care. The aim of this trial is to examine whether antihypertensive medication reduction is possible in older patients without significant changes in blood pressure control at follow-up.Methods and analysisThis trial will use a primary care-based, open-label, randomised controlled trial design. A total of 540 participants will be recruited, aged ≥80 years, with systolic blood pressure Ethics and disseminationThe protocol, informed consent form, participant information sheet and all other participant facing material have been approved by the Research Ethics Committee (South Central—Oxford A; ref 16/SC/0628), Medicines and Healthcare products Regulatory Agency (ref 21584/0371/001–0001), host institution(s) and Health Research Authority. All research outputs will be published in peer-reviewed journals and presented at national and international conferences.Trial registration numberEudraCT 2016-004236-38;ISRCTN97503221; Pre-results.

OBJECTIVES: Evidence to support initiation of pharmacological treatment in patients with uncomplicated (low risk) mild hypertension is inconclusive. As such, clinical guidelines are contradictory and healthcare policy has changed regularly. The aim of this study was to determine the incidence of lifestyle advice and drug therapy in this population and whether secular trends were associated with policy changes. DESIGN: Longitudinal cohort study. SETTING: Primary care practices contributing to the Clinical Practice Research Datalink in England. PARTICIPANTS: Data were extracted from the linked electronic health records of patients aged 18-74 years, with stage 1 hypertension (blood pressure between 140/90 and 159/99 mm Hg), no cardiovascular disease (CVD) risk factors and no treatment, from 1998 to 2015. Patients exited if follow-up records became unavailable, they progressed to stage 2 hypertension, developed a CVD risk factor or received lifestyle advice/treatment. PRIMARY OUTCOME MEASURES: The association between policy changes and incidence of lifestyle advice or treatment, examined using an interrupted time-series analysis. RESULTS: A total of 108 843 patients were defined as having uncomplicated mild hypertension (mean age 51.9±12.9 years, 60.0% female). Patientsspent a median 2.6 years (IQR 0.9-5.5) in the study, after which 12.2% (95% CI 12.0% to 12.4%) were given lifestyle advice, 29.9% (95% CI 29.7% to 30.2%) were prescribed medication and 19.4% (95% CI 19.2% to 19.6%) were given both. The introduction of the quality outcomes framework (QOF) and subsequent changes to QOF indicators were followed by significant increases in the incidence of lifestyle advice. Treatment prescriptions decreased slightly over time, but were not associated with policy changes. CONCLUSIONS: Despite secular trends that accord with UK guidance, many patients are still prescribed treatment for mild hypertension. Adequately powered studies are needed to determine if this is appropriate.

OBJECTIVES: The aim of this study was to examine the impact of transient ischaemic attack (TIA) service modification in two hospitals on costs and clinical outcomes. DESIGN: Discrete event simulation model using data from routine electronic health records from 2011. PARTICIPANTS: Patients with suspected TIA were followed from symptom onset to presentation, referral to specialist clinics, treatment and subsequent stroke. INTERVENTIONS: Included existing versus previous (less same day clinics) and hypothetical service reconfiguration (7-day service with less availability of clinics per day). OUTCOME MEASURES: The primary outcome of the model was the prevalence of major stroke after TIA. Secondary outcomes included service costs (including those of treating subsequent stroke) and time to treatment and attainment of national targets for service provision (proportion of high-risk patients (according to ABCD2 score) seen within 24 hours). RESULTS: The estimated costs of previous service provision for 490 patients (aged 74±12 years, 48.9% female and 23.6% high risk) per year at each site were £340 000 and £368 000, respectively. This resulted in 31% of high-risk patients seen within 24 hours of referral (47/150) with a median time from referral to clinic attendance/treatment of 1.15 days (IQR 0.93-2.88). The costs associated with the existing and hypothetical services decreased by £5000 at one site and increased £21 000 at the other site. Target attainment was improved to 79% (118/150). However, the median time to clinic attendance was only reduced to 0.85 days (IQR 0.17-0.99) and thus no appreciable impact on the modelled incidence of major stroke was observed (10.7 per year, 99% CI 10.5 to 10.9 (previous service) vs 10.6 per year, 99% CI 10.4 to 10.8 (existing service)). CONCLUSIONS: Reconfiguration of services for TIA is effective at increasing target attainment, but in services which are already working efficiently (treating patients within 1-2 days), it has little estimated impact on clinical outcomes and increased investment may not be worthwhile.

Background Self-monitoring of blood pressure (BP) appears to reduce BP in hypertension but important questions remain regarding effective implementation and which groups may benefit most. This individual patient data (IPD) meta-analysis was performed to better understand the effectiveness of BP self-monitoring to lower BP and control hypertension. Methods and findings Medline, Embase, and the Cochrane Library were searched for randomised trials comparing self-monitoring to no self-monitoring in hypertensive patients (9June 2016). Two reviewers independently assessed articles for eligibility and the authors of eligible trials were approached requesting IPD. Of 2,846 articles in the initial search, 36 were eligible. IPD were provided from 25 trials, including 1 unpublished study. Data for the primary outcomes-change in mean clinic or ambulatory BP and proportion controlled below target at 12 months-were available from 15/19 possible studies (97,138/8,292 [86%] of randomised participants). Overall, self-monitoring was associated with reduced clinic systolic blood pressure (9sBP) compared to usual care at 12 months (-3.2 mmHg, [95% CI -4.9, -1.6 mmHg]). However, this effect was strongly influenced by the intensity of co-intervention ranging from no effect with self-monitoring alone (-1.0 mmHg [-3.3, 1.2]), to a 6.1 mmHg (-9.0, -3.2) reduction when monitoring was combined with intensive support. Self-monitoring was most effective in those with fewer antihypertensive medications and higher baseline sBP up to 170 mmHg. No differences in efficacy were seen by sex or by most comorbidities. Ambulatory BP data at 12 months were available from 4 trials (91,478 patients), which assessed selfmonitoring with little or no co-intervention. There was no association between self-monitoring and either lower clinic or ambulatory sBP in this group (9clinic -0.2 mmHg [-2.2, 1.8]; ambulatory 1.1 mmHg [-0.3, 2.5]). Results for diastolic blood pressure (9dBP) were similar. The main limitation of this work was that significant heterogeneity remained. This was at least in part due to different inclusion criteria, self-monitoring regimes, and target BPs in included studies. Conclusions Self-monitoring alone is not associated with lower BP or better control, but in conjunction with co-interventions (9including systematic medication titration by doctors, pharmacists, or patients; education; or lifestyle counselling) leads to clinically significant BP reduction which persists for at least 12 months. The implementation of self-monitoring in hypertension should be accompanied by such co-interventions., This research was funded by the Institute for Health Research School for Primary Care Research (NIHR SPCR number 112) and via an NIHR Professorship for RM (NIHR-RP-02-12-015). JS holds a Medical Research Council (MRC) Strategic Skills Postdoctoral Fellowship (MR/K022032/1). FDRH is part funded as Director of the National Institute for Health Research (NIHR) School for Primary Care Research (SPCR), Theme Leader of the NIHR Oxford Biomedical Research Centre (BRC), and Director of the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) Oxford. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.