Randomised controlled trial of population screening for atrial fibrillation in people aged 70 years and over to reduce stroke: protocol for the SAFER trial.

INTRODUCTION: There is a lack of evidence that the benefits of screening for atrial fibrillation (AF) outweigh the harms. Following the completion of the Screening for Atrial Fibrillation with ECG to Reduce stroke (SAFER) pilot trial, the aim of the main SAFER trial is to establish whether population screening for AF reduces incidence of stroke risk. METHODS AND ANALYSIS: Approximately 82 000 people aged 70 years and over and not on oral anticoagulation are being recruited from general practices in England. Patients on the palliative care register or residents in a nursing home are excluded. Eligible people are identified using electronic patient records from general practices and sent an invitation and consent form to participate by post. Consenting participants are randomised at a ratio of 2:1 (control:intervention) with clustering by household. Those randomised to the intervention arm are sent an information leaflet inviting them to participate in screening, which involves use of a handheld single-lead ECG four times a day for 3 weeks. ECG traces identified by an algorithm as possible AF are reviewed by cardiologists. Participants with AF are seen by a general practitioner for consideration of anticoagulation. The primary outcome is stroke. Major secondary outcomes are: death, major bleeding and cardiovascular events. Follow-up will be via electronic health records for an average of 4 years. The primary analysis will be by intention-to-treat using time-to-event modelling. Results from this trial will be combined with follow-up data from the cluster-randomised pilot trial by fixed-effects meta-analysis. ETHICS AND DISSEMINATION: The London-Central National Health Service Research Ethics Committee (19/LO/1597) provided ethical approval. Dissemination will include public-friendly summaries, reports and engagement with the UK National Screening Committee. TRIAL REGISTRATION NUMBER: ISRCTN72104369.

Sociodemographic characteristics and longitudinal progression of multimorbidity: A multistate modelling analysis of a large primary care records dataset in England.

BACKGROUND: Multimorbidity, characterised by the coexistence of multiple chronic conditions in an individual, is a rising public health concern. While much of the existing research has focused on cross-sectional patterns of multimorbidity, there remains a need to better understand the longitudinal accumulation of diseases. This includes examining the associations between important sociodemographic characteristics and the rate of progression of chronic conditions. METHODS AND FINDINGS: We utilised electronic primary care records from 13.48 million participants in England, drawn from the Clinical Practice Research Datalink (CPRD Aurum), spanning from 2005 to 2020 with a median follow-up of 4.71 years (IQR: 1.78, 11.28). The study focused on 5 important chronic conditions: cardiovascular disease (CVD), type 2 diabetes (T2D), chronic kidney disease (CKD), heart failure (HF), and mental health (MH) conditions. Key sociodemographic characteristics considered include ethnicity, social and material deprivation, gender, and age. We employed a flexible spline-based parametric multistate model to investigate the associations between these sociodemographic characteristics and the rate of different disease transitions throughout multimorbidity development. Our findings reveal distinct association patterns across different disease transition types. Deprivation, gender, and age generally demonstrated stronger associations with disease diagnosis compared to ethnic group differences. Notably, the impact of these factors tended to attenuate with an increase in the number of preexisting conditions, especially for deprivation, gender, and age. For example, the hazard ratio (HR) (95% CI; p-value) for the association of deprivation with T2D diagnosis (comparing the most deprived quintile to the least deprived) is 1.76 ([1.74, 1.78]; p < 0.001) for those with no preexisting conditions and decreases to 0.95 ([0.75, 1.21]; p = 0.69) with 4 preexisting conditions. Furthermore, the impact of deprivation, gender, and age was typically more pronounced when transitioning from an MH condition. For instance, the HR (95% CI; p-value) for the association of deprivation with T2D diagnosis when transitioning from MH is 2.03 ([1.95, 2.12], p < 0.001), compared to transitions from CVD 1.50 ([1.43, 1.58], p < 0.001), CKD 1.37 ([1.30, 1.44], p < 0.001), and HF 1.55 ([1.34, 1.79], p < 0.001). A primary limitation of our study is that potential diagnostic inaccuracies in primary care records, such as underdiagnosis, overdiagnosis, or ascertainment bias of chronic conditions, could influence our results. CONCLUSIONS: Our results indicate that early phases of multimorbidity development could warrant increased attention. The potential importance of earlier detection and intervention of chronic conditions is underscored, particularly for MH conditions and higher-risk populations. These insights may have important implications for the management of multimorbidity.

Progression of stroke risk in patients aged <65 years diagnosed with atrial fibrillation: a cohort study in general practice.

BACKGROUND: As a result of new technologies, atrial fibrillation (AF) is more likely to be diagnosed in people aged <65 years. AIM: To investigate the risk of someone diagnosed with AF aged <65 years developing an indication for anticoagulation before they reach 65 years. DESIGN AND SETTING: Population-based cohort study of patients from English practices using the Clinical Practice Research Datalink, a primary care database of electronic medical records. METHOD: The study included patients aged <65 years newly diagnosed with AF. The CHA2DS2-VASc score was derived at time of diagnosis based on patients' medical records. Patients not eligible for anticoagulation were followed up until they became eligible or turned 65 years old. The primary outcome of interest was development of a risk factor for stroke in AF. RESULTS: Among 18 178 patients aged <65 years diagnosed with AF, 9188 (50.5%) were eligible for anticoagulation at the time of diagnosis. Among the 8990 patients not eligible for anticoagulation, 1688 (18.8%) developed a risk factor during follow-up before reaching 65 years of age or leaving the cohort for other reasons, at a rate of 6.1 per 100 patient-years. Hypertension and heart failure were the most common risk factors to occur, with rates of 2.65 (95% CI = 2.47 to 2.84) and 1.58 (95% CI = 1.45 to 1.72) per 100 patient-years, respectively. The rate of new diabetes was 0.95 (95% CI = 0.85 to 1.06) per 100 patient-years. CONCLUSION: People aged <65 years with AF are at higher risk of developing hypertension, heart failure, and diabetes than the general population, so may warrant regular review to identify new occurrence of such risk factors.

In simulated data and health records, latent class analysis was the optimum multimorbidity clustering algorithm.

BACKGROUND AND OBJECTIVES: To investigate the reproducibility and validity of latent class analysis (LCA) and hierarchical cluster analysis (HCA), multiple correspondence analysis followed by k-means (MCA-kmeans) and k-means (kmeans) for multimorbidity clustering. METHODS: We first investigated clustering algorithms in simulated datasets with 26 diseases of varying prevalence in predetermined clusters, comparing the derived clusters to known clusters using the adjusted Rand Index (aRI). We then them investigated the medical records of male patients, aged 65 to 84 years from 50 UK general practices, with 49 long-term health conditions. We compared within cluster morbidity profiles using the Pearson correlation coefficient and assessed cluster stability using in 400 bootstrap samples. RESULTS: In the simulated datasets, the closest agreement (largest aRI) to known clusters was with LCA and then MCA-kmeans algorithms. In the medical records dataset, all four algorithms identified one cluster of 20-25% of the dataset with about 82% of the same patients across all four algorithms. LCA and MCA-kmeans both found a second cluster of 7% of the dataset. Other clusters were found by only one algorithm. LCA and MCA-kmeans clustering gave the most similar partitioning (aRI 0.54). CONCLUSION: LCA achieved higher aRI than other clustering algorithms.

Statin use is associated with lower risk of dementia in stroke patients: a community-based cohort study with inverse probability weighted marginal structural model analysis.

Current evidence is inconclusive on cognitive benefits or harms of statins among stroke patients, who have high risk of dementia. This observational cohort study investigated the association between statin use and post-stroke dementia using data from the Clinical Practice Research Datalink. Patients without prior dementia who had an incident stroke but received no statins in the preceding year were followed for up to 10 years. We used inverse probability weighted marginal structural models to estimate observational analogues of intention-to-treat (ITT, statin initiation vs. no initiation) and per-protocol (PP, sustained statin use vs. no use) effects on the risk of dementia. To explore potential impact of unmeasured confounding, we examined the risks of coronary heart disease (CHD, positive control outcome), fracture and peptic ulcer (negative control outcomes). In 18,577 statin initiators and 14,613 non-initiators (mean follow-up of 4.2 years), the adjusted hazard ratio (aHR) for dementia was 0.70 (95% confidence interval [CI] 0.64-0.75) in ITT analysis and 0.55 (95% CI 0.50-0.62) in PP analysis. The corresponding aHRITT and aHRPP were 0.87 (95% CI 0.79-0.95) and 0.70 (95% CI 0.62-0.80) for CHD, 1.03 (95% CI 0.82-1.29) and 1.09 (95% CI 0.77-1.54) for peptic ulcer, and 0.88 (95% CI 0.80-0.96) and 0.86 (95% CI 0.75-0.98) for fracture. Statin initiation after stroke was associated with lower risk of dementia, with a potentially greater benefit in patients who persisted with statins over time. The observed association of statin use with post-stroke dementia may in part be overestimated due to unmeasured confounding shared with the association between statin use and fracture.

Association of major blood lipids with post-stroke dementia: A community-based cohort study.

BACKGROUND AND PURPOSE: The roles of blood low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides in the development of post-stroke dementia remain uncertain. This study was to investigate their potential associations. METHODS: A retrospective cohort study was conducted using the Clinical Practice Research Datalink. Patients with first-ever stroke but no prior dementia were followed up for 10 years. Cox regression was used to examine the association of baseline LDL-C, HDL-C and triglycerides with post-stroke dementia. RESULTS: Amongst 63,959 stroke patients, 15,879 had complete baseline data and were included in our main analysis. 10.8% developed dementia during a median of 4.6 years of follow-up. The adjusted hazard ratio of dementia for LDL-C (per log mmol/l increase) was 1.29 (95% confidence interval [CI] 1.14-1.47), with a linear increasing trend (p trend <0.001). The counterpart for triglycerides was 0.79 (95% CI 0.69-0.89), with a linear decreasing trend (p trend <0.001). For HDL-C, there was no association with dementia (adjusted hazard ratio 0.89, 95% CI 0.74-1.08) or a linear trend (p trend = 0.22). CONCLUSIONS: Blood lipids may affect the risk of post-stroke dementia in different ways, with higher risk associated with LDL-C, lower risk associated with triglycerides, and no association with HDL-C.

Cluster randomised controlled trial of screening for atrial fibrillation in people aged 70 years and over to reduce stroke: protocol for the pilot study for the SAFER trial.

INTRODUCTION: Atrial fibrillation (AF) is a common arrhythmia associated with 30% of strokes, as well as other cardiovascular disease, dementia and death. AF meets many criteria for screening, but there is limited evidence that AF screening reduces stroke. Consequently, no countries recommend national screening programmes for AF. The Screening for Atrial Fibrillation with ECG to Reduce stroke (SAFER) trial aims to determine whether screening for AF is effective at reducing risk of stroke. The aim of the pilot study is to assess feasibility of the main trial and inform implementation of screening and trial procedures. METHODS AND ANALYSIS: SAFER is planned to be a pragmatic randomised controlled trial (RCT) of over 100 000 participants aged 70 years and over, not on long-term anticoagulation therapy at baseline, with an average follow-up of 5 years. Participants are asked to record four traces every day for 3 weeks on a hand-held single-lead ECG device. Cardiologists remotely confirm episodes of AF identified by the device algorithm, and general practitioners follow-up with anticoagulation as appropriate. The pilot study is a cluster RCT in 36 UK general practices, randomised 2:1 control to intervention, recruiting approximately 12 600 participants. Pilot study outcomes include AF detection rate, anticoagulation uptake and other parameters to incorporate into sample size calculations for the main trial. Questionnaires sent to a sample of participants will assess impact of screening on psychological health. Process evaluation and qualitative studies will underpin implementation of screening during the main trial. An economic evaluation using the pilot data will confirm whether it is plausible that screening might be cost-effective. ETHICS AND DISSEMINATION: The London-Central Research Ethics Committee (19/LO/1597) and Confidentiality Advisory Group (19/CAG/0226) provided ethical approval. Dissemination will be via publications, patient-friendly summaries, reports and engagement with the UK National Screening Committee. TRIAL REGISTRATION NUMBER: ISRCTN72104369.

Characteristics of patients with heart failure with preserved ejection fraction in primary care: a cross-sectional analysis.

BACKGROUND: Many patients with heart failure with preserved ejection fraction (HFpEF) are undiagnosed, and UK general practice registers do not typically record heart failure (HF) subtype. Improvements in management of HFpEF is dependent on improved identification and characterisation of patients in primary care. AIM: To describe a cohort of patients recruited from primary care with suspected HFpEF and compare patients in whom HFpEF was confirmed and refuted. DESIGN & SETTING: Baseline data from a longitudinal cohort study of patients with suspected HFpEF recruited from primary care in two areas of England. METHOD: A screening algorithm and review were used to find patients on HF registers without a record of reduced ejection fraction (EF). Baseline evaluation included cardiac, mental and physical function, clinical characteristics, and patient reported outcomes. Confirmation of HFpEF was clinically adjudicated by a cardiologist. RESULTS: In total, 93 (61%) of 152 patients were confirmed HFpEF. The mean age of patients with HFpEF was 79 years, 46% were female, 80% had hypertension, and 37% took ≥10 medications. Patients with HFpEF were more likely to be obese, pre-frail or frail, report more dyspnoea and fatigue, were more functionally impaired, and less active than patients in whom HFpEF was refuted. Few had attended cardiac rehabilitation. CONCLUSION: Patients with confirmed HFpEF had frequent multimorbidity, functional impairment, frailty, and polypharmacy. Although comorbid conditions were similar between people with and without HFpEF, the former had more obesity, symptoms, and worse physical function. These findings highlight the potential to optimise wellbeing through comorbidity management, medication rationalisation, rehabilitation, and supported self-management.

Anticoagulation trends in adults aged 65 years and over with atrial fibrillation: a cohort study.

OBJECTIVE: To describe patterns of anticoagulation prescription and persistence for those aged ≥65 years with atrial fibrillation (AF). METHODS: Descriptive cohort study using electronic general practice records of patients in England, who attended an influenza vaccination aged ≥65 years and were diagnosed with AF between 2008 and 2018. Patients were stratified by 10-year age group and year of diagnosis. Proportion anticoagulated, type of anticoagulation (direct oral anticoagulant (DOAC) or warfarin) initiated at diagnosis and persistence with anticoagulation over time are reported. RESULTS: 42 290 patients (49% female), aged 65-74 (n=11 722), 75-84 (n=19 055) and 85+ (n=11 513) years at AF diagnosis are included. Prescription of anticoagulation at diagnosis increased over the time period from 55% to 86% in people aged 65-74 years, from 54% to 86% in people aged 75-84 years and from 27% to 75% in people aged 85 years and over. By 2018, 92% of patients with newly diagnosed AF were started on a DOAC. Survivor function for 5-year persistence in patients prescribed DOAC was 0.80 (95% CI 0.77 to 0.82) and for warfarin 0.71 (95% CI 0.70 to 0.72). Survivor function for any anticoagulation at 5 years was 0.79 (95% CI 0.78 to 0.81), 0.73 (95% CI 0.72 to 0.75) and 0.58 (95% CI 0.59 to 0.64) for people aged 65-74, 75-84 and 85+ years, respectively. CONCLUSIONS: Rates of anticoagulation in AF in those aged ≥65 years have increased from 2008 to 2018, over which time period there has been a shift from initiating anticoagulation with warfarin to DOAC. Persistence with anticoagulation is higher in people on DOACs than on warfarin and in people aged <85 years.

Use of Primary Care Data in Research and Pharmacovigilance: Eight Scenarios Where Prescription Data are Absent.

The use of primary care databases has been integral in pharmacoepidemiological studies and pharmacovigilance. Primary care databases derive from electronic health records and offer a comprehensive description of aggregate patient data, from demography to medication history, and good sample sizes. Studies using these databases improve our understanding of prescribing characteristics and associated risk factors to facilitate better patient care, but there are limitations. We describe eight key scenarios where study data outcomes can be affected by absent prescriptions in UK primary care databases: (1) out-of-hours, urgent care and acute care prescriptions; (2) specialist-only prescriptions; (3) alternative community prescribing, such as pharmacy, family planning clinic or sexual health clinic medication prescriptions; (4) newly licensed medication prescriptions; (5) medications that do not require prescriptions; (6) hospital inpatient and outpatient prescriptions; (7) handwritten prescriptions; and (8) private pharmacy and private doctor prescriptions. The significance of each scenario is dependent on the type of medication under investigation, nature of the study and expected outcome measures. We recommend that all researchers using primary care databases be aware of the potential for missing prescribing data and be sensitive to how this can vary substantially between items, drug classes, patient groups and over time. Close liaison with practising primary care clinicians in the UK is often essential to ensure awareness of nuances in clinical practice.

Temporal trends in incidence of atrial fibrillation in primary care records: a population-based cohort study.

OBJECTIVES: Atrial fibrillation (AF) is a heart condition associated with a fivefold increased risk of stroke. The condition can be detected in primary care and treatment can greatly reduce the risk of stroke. In recent years, a number of policy initiatives have tried to improve diagnosis and treatment of AF, including local National Health Service schemes and the Quality and Outcomes Framework. We aimed to examine trends in the incidence of recorded AF in primary care records from English practices between 2004 and 2018. DESIGN: Longitudinal cohort study. SETTING: English primary care electronic health records linked to Index of Multiple Deprivation data. PARTICIPANTS: Cohort of 3.5 million patients over 40 years old registered in general practices in England, contributing 22 million person-years of observation between 2004 and 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: Incident AF was identified through newly recorded AF codes in the patients' records. Yearly incidence rates were stratified by gender, age group and a measure of deprivation. RESULTS: Incidence rates were stable before 2010 and then rose and peaked in 2015 at 5.07 (95% CI 4.94 to 5.20) cases per 1000 person-years. Incidence was higher in males (4.95 (95% CI 4.91 to 4.99) cases per 1000 person-years vs 4.12 (95% CI 4.08 to 4.16) in females) and rises markedly with age (0.58 (95% CI 0.56 to 0.59) cases per 1000 person-years in 40-54 years old vs 21.7 (95% CI 21.4 to 22.0) cases in over 85s). The increase in incidence over time was observed mainly in people over the age of 75, particularly men. There was no evidence that temporal trends in incidence were associated with deprivation. CONCLUSIONS: Changes in clinical practice and policy initiatives since 2004 have been associated with increased rates of diagnosis of AF up until 2015, but rates declined from 2015 to 2018.

Association of Prior Atherosclerotic Cardiovascular Disease with Dementia After Stroke: A Retrospective Cohort Study.

BACKGROUND: Prior atherosclerotic cardiovascular disease (ASCVD), including coronary heart disease (CHD) and peripheral artery disease (PAD), are common among patients with stroke, a known risk factor for dementia. However, whether these conditions further increase the risk of post-stroke dementia remains uncertain. OBJECTIVE: To examine whether prior ASCVD is associated with increased risk of dementia among stroke patients. METHODS: A retrospective cohort study was conducted using the Clinical Practice Research Datalink with linkage to hospital data. Patients with first-ever stroke between 2006 and 2017 were followed up to 10 years. We used multi-variable Cox regression models to examine the associations of prior ASCVD with dementia and the impact of prior ASCVD onset and duration. RESULTS: Among 63,959 patients, 7,265 cases (11.4%) developed post-stroke dementia during a median of 3.6-year follow-up. The hazard ratio (HR) of dementia adjusted for demographics and lifestyle was 1.18 (95% CI: 1.12-1.25) for ASCVD, 1.16 (1.10-1.23) for CHD, and 1.25 (1.13-1.37) for PAD. The HRs additionally adjusted for multimorbidity and medications were 1.07 (1.00-1.13), 1.04 (0.98-1.11), and 1.11 (1.00-1.22), respectively. Based on the fully adjusted estimates, there was no linear relationship between the age of ASCVD onset and post-stroke dementia (all p-trend >0.05). The adjusted risk of dementia was not increased with the duration of pre-stroke ASCVD (all p-trend >0.05). CONCLUSION: Stroke patients with prior ASCVD are more likely to develop subsequent dementia. After full adjustment for confounding, however, the risk of post-stroke dementia is attenuated, with only a slight increase with prior ASCVD.

Characteristics, service use and mortality of clusters of multimorbid patients in England: a population-based study.

BACKGROUND: Multimorbidity is associated with mortality and service use, with specific types of multimorbidity having differential effects. Additionally, multimorbidity is often negatively associated with participation in research cohorts. Therefore, we set out to identify clusters of multimorbidity patients and how they are differentially associated with mortality and service use across age groups in a population-representative sample. METHODS: Linked primary and secondary care electronic health records contributed by 382 general practices in England to the Clinical Practice Research Datalink (CPRD) were used. The study included a representative set of multimorbid adults (18 years old or more, N = 113,211) with two or more long-term conditions (a total of 38 conditions were included). A random set of 80% of the multimorbid patients (N = 90,571) were stratified by age groups and clustered using latent class analysis. Consistency between obtained multimorbidity phenotypes, classification quality and associations with demographic characteristics and primary outcomes (GP consultations, hospitalisations, regular medications and mortality) was validated in the remaining 20% of multimorbid patients (N = 22,640). RESULTS: We identified 20 patient clusters across four age strata. The clusters with the highest mortality comprised psychoactive substance and alcohol misuse (aged 18-64); coronary heart disease, depression and pain (aged 65-84); and coronary heart disease, heart failure and atrial fibrillation (aged 85+). The clusters with the highest service use coincided with those with the highest mortality for people aged over 65. For people aged 18-64, the cluster with the highest service use comprised depression, anxiety and pain. The majority of 85+-year-old multimorbid patients belonged to the cluster with the lowest service use and mortality for that age range. Pain featured in 13 clusters. CONCLUSIONS: This work has highlighted patterns of multimorbidity that have implications for health services. These include the importance of psychoactive substance and alcohol misuse in people under the age of 65, of co-morbid depression and coronary heart disease in people aged 65-84 and of cardiovascular disease in people aged 85+.

Development and validation of the Cambridge Multimorbidity Score.

BACKGROUND: Health services have failed to respond to the pressures of multimorbidity. Improved measures of multimorbidity are needed for conducting research, planning services and allocating resources. METHODS: We modelled the association between 37 morbidities and 3 key outcomes (primary care consultations, unplanned hospital admission, death) at 1 and 5 years. We extracted development (n = 300 000) and validation (n = 150 000) samples from the UK Clinical Practice Research Datalink. We constructed a general-outcome multimorbidity score by averaging the standardized weights of the separate outcome scores. We compared performance with the Charlson Comorbidity Index. RESULTS: Models that included all 37 conditions were acceptable predictors of general practitioner consultations (C-index 0.732, 95% confidence interval [CI] 0.731-0.734), unplanned hospital admission (C-index 0.742, 95% CI 0.737-0.747) and death at 1 year (C-index 0.912, 95% CI 0.905-0.918). Models reduced to the 20 conditions with the greatest combined prevalence/weight showed similar predictive ability (C-indices 0.727, 95% CI 0.725-0.728; 0.738, 95% CI 0.732-0.743; and 0.910, 95% CI 0.904-0.917, respectively). They also predicted 5-year outcomes similarly for consultations and death (C-indices 0.735, 95% CI 0.734-0.736, and 0.889, 95% CI 0.885-0.892, respectively) but performed less well for admissions (C-index 0.708, 95% CI 0.705-0.712). The performance of the general-outcome score was similar to that of the outcome-specific models. These models performed significantly better than those based on the Charlson Comorbidity Index for consultations (C-index 0.691, 95% CI 0.690-0.693) and admissions (C-index 0.703, 95% CI 0.697-0.709) and similarly for mortality (C-index 0.907, 95% CI 0.900-0.914). INTERPRETATION: The Cambridge Multimorbidity Score is robust and can be either tailored or not tailored to specific health outcomes. It will be valuable to those planning clinical services, policymakers allocating resources and researchers seeking to account for the effect of multimorbidity.

Association of blood lipids, atherosclerosis and statin use with dementia and cognitive impairment after stroke: A systematic review and meta-analysis.

BACKGROUND: Trial and observational evidence is conflicting in terms of the association of blood lipids, atherosclerosis and statin use with dementia and cognitive impairment in the general population. It is uncertain whether the associations occur in stroke patients, who are at known higher risk of cognitive decline. This systematic review was to synthesize the evidence for these associations among stroke patients. METHODS: MEDLINE, EMBASE, the Cochrane Library and trial registries were searched. We included randomized controlled trials (RCTs) or observational cohort studies conducted among patients with stroke and reported on the association of blood lipids, atherosclerosis or statin use with dementia or cognitive impairment. Meta-analysis was conducted separately for crude and maximally adjusted odds ratios (ORs) and hazard ratios (HRs). RESULTS: Of 18,026 records retrieved, 56 studies (one RCT and 55 cohort studies) comprising 38,423 stroke patients were included. For coronary heart disease, the pooled OR of dementia and cognitive impairment was 1.32 (95%CI 1.10-1.58, n = 15 studies, I2 = 0%) and 1.23 (95%CI 0.99-1.54, n = 14, I2 = 26.9%), respectively. Peripheral artery disease was associated with dementia (OR 3.59, 95%CI 1.47-8.76, n = 2, I2 = 0%) and cognitive impairment (OR 2.70, 95%CI 1.09-6.69, n = 1). For carotid stenosis, the pooled OR of dementia and cognitive impairment was 2.67 (95%CI 0.83-8.62, n = 3, I2 = 77.9%) and 3.34 (95%CI 0.79-14.1, n = 4, I2 = 96.6%), respectively. For post-stroke statin use, the pooled OR of dementia and cognitive impairment was 0.89 (95%CI 0.65-1.21, n = 1) and 0.56 (95%CI 0.46-0.69, n = 3, I2 = 0%), respectively. No association was observed for hypercholesterolemia. These results were mostly consistent with adjusted ORs or HRs, which were reported from limited evidence. CONCLUSION: Atherosclerosis was associated with an increased risk of post-stroke dementia. Post-stroke statin use was associated with decreased risk of cognitive impairment. To confirm whether or not statins confer advantages in the post-stroke population in terms of preventing cognitive decline over and above their known effectiveness in reducing risk of further vascular events, further stroke trials including cognitive assessment and observational analyses adjusted for key confounders, focusing on key subgroups or statin use patterns are required.

Optimising Management of Patients with Heart Failure with Preserved Ejection Fraction in Primary Care (OPTIMISE-HFpEF): rationale and protocol for a multi-method study.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is less well understood than heart failure with reduced ejection fraction (HFrEF), with greater diagnostic difficulty and management uncertainty. AIM: The primary aim is to develop an optimised programme that is informed by the needs and experiences of people with HFpEF and healthcare providers. This article presents the rationale and protocol for the Optimising Management of Patients with Heart Failure with Preserved Ejection Fraction in Primary Care (OPTIMISE-HFpEF) research programme. DESIGN & SETTING: This is a multi-method programme of research conducted in the UK. METHOD: OPTIMISE-HFpEF is a multi-site programme of research with three distinct work packages (WPs). WP1 is a systematic review of heart failure disease management programmes (HF-DMPs) tested in patients with HFpEF. WP2 has three components (a, b, c) that enable the characteristics, needs, and experiences of people with HFpEF, their carers, and healthcare providers to be understood. Qualitative enquiry (WP2a) with patients and providers will be conducted in three UK sites exploring patient and provider perspectives, with an additional qualitative component (WP2c) in one site to focus on transitions in care and carer perspectives. A longitudinal cohort study (WP2b), recruiting from four UK sites, will allow patients to be characterised and their illness trajectory observed across 1 year of follow-up. Finally, WP3 will synthesise the findings and conduct work to gain consensus on how best to identify and manage this patient group. RESULTS: Results from the four work packages will be synthesised to produce a summary of key learning points and possible solutions (optimised programme) which will be presented to a broad spectrum of stakeholders to gain consensus on a way forward. CONCLUSION: HFpEF is often described as the greatest unmet need in cardiology. The OPTIMISE-HFpEF programme aims to address this need in primary care, which is arguably the most appropriate setting for managing HFpEF.

Statin use and high-dose statin use after ischemic stroke in the UK: a retrospective cohort study.

Background: Trial evidence supports statin use after ischemic stroke and recent American, European and British guidelines recommend high-intensity statins for this indication. Limited data are available describing current statin use among these patients in unselected settings. We conducted a cohort study to examine secular trends and factors associated with statin use and dose following ischemic stroke. Methods: A retrospective cohort study of patients with first ischemic stroke between 2000 and 2014 was conducted using the Clinical Practice Research Datalink (CPRD). Proportions of statin users and high-intensity statin users within 2 years after stroke were estimated for each calendar year. We used Cox regression models to explore potential factors associated with statin use and Poisson regression models to calculate risk ratios for the use of a high-intensity statin. Results: A total of 80,442 patients with first stroke were analyzed. The proportion using statins within 2 years after stroke increased from 25% in 2000 to 70% in 2006 and remained at about 75% through 2014. Among post-stroke statin users, high-intensity use accounted for approximately 15% between 2004 and 2011 and then increased to almost 35% in 2014. Older patients (aged ≥75 years), younger patients (<45 years), patients with no prior statin treatment, dementia, underweight, or absence of cardiovascular factors (coronary heart disease, smoking, obesity, diabetes, hypertension, or transient ischemic attack) were less likely to use statins and less likely to receive a high-intensity statin. Conclusion: There has been an increase over time in both statin use and dose, but many patients with ischemic stroke continue to be under-treated. Clinical trials and policy interventions to improve appropriate post-stroke statin use should focus on younger and older patients, patients with no pre-stroke statin treatment, and patients without additional cardiovascular risk factors.

The role of the GP in managing suspected transient ischaemic attack: a qualitative study.

BACKGROUND: National guidelines recommend patients with suspected transient ischaemic attack (TIA) should be seen by a specialist within 24 h. However, people with suspected TIA often present to non-specialised services, particularly primary care. Therefore, general practitioners (GPs) have a crucial role in recognition and urgent referral of people with suspected TIA. This study aims to explore the role of GPs in the initial management of suspected TIA in the United Kingdom (UK). METHODS: One-to-one, semi-structured interviews with GPs, TIA clinic staff and patients with suspected TIA from two sites in the UK: Cambridge and Birmingham. Thematic analysis was undertaken to explore views on the role of the GP in managing suspected TIA. Thirty semi-structured interviews were conducted with stroke patients (n = 12), GPs (n = 9) and TIA clinic hospital staff (n = 9) from two hospitals and nine GP practices in surrounding areas. RESULTS: Three overarching themes were identified: (1) multiple management pathways for suspected TIA; (2) uncertainty regarding suspected TIA as an emergency or routine situation; and (3) influences on the urgency of GP management. CONCLUSIONS: Guidelines on the primary care management of TIA describe only a small proportion of the factors which influence GP management and referral of suspected TIA. Efforts to improve treatment, appropriate referral and patient experience should use a real rather than idealised model of the GP role in managing suspected TIA.

The tip of the iceberg: finding patients with heart failure with preserved ejection fraction in primary care. An observational study.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is under-identified in primary care. AIM: The aim of this study was to determine what information is available in patients' primary care practice records that would identify patients with HFpEF. DESIGN & SETTING: Record review in two practices in east of England. METHOD: Practices completed a case report form on each patient on the heart failure register and sent anonymised echocardiography reports on patients with an ejection fraction (EF) >50%. Reports were reviewed and data analysed using SPSS (version 25). RESULTS: One hundred and forty-eight patients on the heart failure registers with mean age 77 +12 years were reviewed. Fifty-three patients (36%) had possible HFpEF based on available information. These patients were older and multimorbid, with a high prevalence of overweight and obesity. Confirmation of diagnosis was not possible as recommended HFpEF diagnostic information (natriuretic peptides, echocardiogram parameters of structural heart disease and diastolic function) was widely inconsistent or absent in these patients. CONCLUSION: Without correct identification of HFpEF, patient management may be suboptimal or inappropriate, and lack the needed focus on comorbidities and lifestyle that can improve patient outcomes. This study describes in detail the characteristics of many of the patients who probably have HFpEF in a real-world sample, and the improvements and diagnostic information required to better identify them. Identifying more than the tip of the iceberg that is the HFpEF population will allow the improvement of the quality of their management, the prevention of ineffective health care, and the recruitment of patients into research.

The epidemiology of multimorbidity in primary care: a retrospective cohort study.

BACKGROUND: Multimorbidity places a substantial burden on patients and the healthcare system, but few contemporary epidemiological data are available. AIM: To describe the epidemiology of multimorbidity in adults in England, and quantify associations between multimorbidity and health service utilisation. DESIGN AND SETTING: Retrospective cohort study, undertaken in England. METHOD: The study used a random sample of 403 985 adult patients (aged ≥18 years), who were registered with a general practice on 1 January 2012 and included in the Clinical Practice Research Datalink. Multimorbidity was defined as having two or more of 36 long-term conditions recorded in patients' medical records, and associations between multimorbidity and health service utilisation (GP consultations, prescriptions, and hospitalisations) over 4 years were quantified. RESULTS: In total, 27.2% of the patients involved in the study had multimorbidity. The most prevalent conditions were hypertension (18.2%), depression or anxiety (10.3%), and chronic pain (10.1%). The prevalence of multimorbidity was higher in females than males (30.0% versus 24.4% respectively) and among those with lower socioeconomic status (30.0% in the quintile with the greatest levels of deprivation versus 25.8% in that with the lowest). Physical-mental comorbidity constituted a much greater proportion of overall morbidity in both younger patients (18-44 years) and those patients with a lower socioeconomic status. Multimorbidity was strongly associated with health service utilisation. Patients with multimorbidity accounted for 52.9% of GP consultations, 78.7% of prescriptions, and 56.1% of hospital admissions. CONCLUSION: Multimorbidity is common, socially patterned, and associated with increased health service utilisation. These findings support the need to improve the quality and efficiency of health services providing care to patients with multimorbidity at both practice and national level.