Management of lipid-lowering therapy in patients with cardiovascular events in the UK: a retrospective cohort study

Objectives To describe low-density lipoprotein (LDL) cholesterol management and lipid-lowering treatment patterns in patients with a cardiovascular (CV) event. Design Retrospective cohort study using Clinical Practice Research Datalink records linked with Hospital Episode Statistics data. Setting Routine clinical practice in the UK from 2006 to 2012. Participants Individuals ≥18 years were selected at their first CV-related hospitalisation (first event cohort) if they had received ≥2 lipid-lowering therapy prescriptions within 180 days beforehand. Patients were stratified into four mutually exclusive subgroups based on the presence or absence of vascular disease and of diabetes. Those with a second CV hospitalisation within 36 months were included in a separate cohort (second event cohort). Primary and secondary outcome measures LDL levels in the year prior to the CV event and 12 months later as well as measures of adherence to lipid-lowering therapy during the 12 months after the CV hospitalisation. Results There were 24 093 patients in the first event cohort, of whom 5274 were included in the second event cohort. Most received moderate intensity statins at baseline and 12 months. Among the four first event cohort subgroups at baseline, the proportions with an LDL of <1.8 mmol/L was similar between the two diabetic cohorts (36% to 38%) and were higher than those in the two non-diabetic cohorts (17% to 22%) and in the second event cohort (31%). An incremental 5% to 9% had an LDL below 1.8 mmol/L at 12 months, suggesting intensification of therapy. The proportion of adherent patients (medication possession ratio of≥0.8) was highest for statins, ranging from 68% to 72%. For ezetimibe, the range was 65% to 70%, and for fibrates, it was 48% to 62%. Conclusions Despite the existence of effective therapies for lowering cholesterol, patients do not reach achievable LDL targets

Comparison of non-laser and laser transvenous lead extraction: a systematic review and meta-analysis.

BACKGROUND: Transvenous lead extraction (TLE) is performed using non-laser and laser techniques with overall high efficacy and safety. Variation in outcomes between the two approaches does exist with limited comparative evidence in the literature. AIM: We sought to compare non-laser and laser TLE in a meta-analysis. METHODS: We searched Medline, Embase, Scopus, ClinicalTrials.gov and CENTRAL databases for TLE studies published between 1991-2021. From the included 68 studies, safety and efficacy data was carefully evaluated and extracted. Aggregated cases of outcomes were used to calculate odds ratio (OR) and pooled rates were synthesised from eligible studies, to compare non-laser and laser techniques. Subgroup comparison of rotational tool and laser extraction was also performed. RESULTS: Non-laser in comparison to laser had lower procedural mortality (pooled rate 0% vs 0.1%, p < 0.01), major complications (pooled rate 0.7% vs 1.7%, p < 0.01) and superior vena cava (SVC) injury (pooled rate 0% vs 0.5%, p < 0.001), with higher complete success (pooled rate 96.5% vs 93.8%, p < 0.01). Non-laser comparatively to laser was more likely to achieve clinical (OR 2.16 [1.77-2.63], p < 0.01) and complete (OR 1.87 [1.69-2.08], p < 0.01) success, with a lower procedural mortality risk (OR 1.6 [1.02-2.5], p < 0.05). In the subgroup analysis, rotational tool compared to laser achieved greater complete success (pooled rate 97.4% vs 95%, p < 0.01) with lower SVC injury (pooled rate 0% vs 0.7%, p < 0.01). CONCLUSION: Non-laser TLE is associated with a better safety and efficacy profile when compared to laser methods. There is a greater risk of SVC injury associated with laser sheath extraction

The use of a bayesian hierarchy to develop and validate a co-morbidity score to predict mortality for linked primary and secondary care data from the NHS in England

Background: We have assessed whether the linkage between routine primary and secondary care records provided an opportunity to develop an improved population based co-morbidity score with the combined information on co-morbidities from both health care settings. Methods: We extracted all people older than 20 years at the start of 2005 within the linkage between the Hospital Episodes Statistics, Clinical Practice Research Datalink, and Office for National Statistics death register in England. A random 50% sample was used to identify relevant diagnostic codes using a Bayesian hierarchy to share information between similar Read and ICD 10 code groupings. Internal validation of the score was performed in the remaining 50% and discrimination was assessed using Harrell’s C statistic. Comparisons were made over time, age, and consultation rate with the Charlson and Elixhauser indexes. Results: 657,264 people were followed up from the 1st January 2005. 98 groupings of codes were derived from the Bayesian hierarchy, and 37 had an adjusted weighting of greater than zero in the Cox proportional hazards model. 11 of these groupings had a different weighting dependent on whether they were coded from hospital or primary care. The C statistic reduced from 0.88 (95% confidence interval 0.88–0.88) in the first year of follow up, to 0.85 (0.85–0.85) including all 5 years. When we stratified the linked score by consultation rate the association with mortality remained consistent, but there was a significant interaction with age, with improved discrimination and fit in those under 50 years old (C=0.85, 0.83–0.87) compared to the Charlson (C=0.79, 0.77–0.82) or Elixhauser index (C=0.81, 0.79–0.83). Conclusions: The use of linked population based primary and secondary care data developed a co-morbidity score that had improved discrimination, particularly in younger age groups, and had a greater effect when adjusting for co-morbidity than existing scores

Life expectancy associated with different ages at diagnosis of type 2 diabetes in high-income countries: 23 million person-years of observation

Background: The prevalence of type 2 diabetes is increasing rapidly, particularly among younger age groups. Estimates suggest that people with diabetes die, on average, 6 years earlier than people without diabetes. We aimed to provide reliable estimates of the associations between age at diagnosis of diabetes and all-cause mortality, cause-specific mortality, and reductions in life expectancy. Methods: For this observational study, we conducted a combined analysis of individual-participant data from 19 high-income countries using two large-scale data sources: the Emerging Risk Factors Collaboration (96 cohorts, median baseline years 1961–2007, median latest follow-up years 1980–2013) and the UK Biobank (median baseline year 2006, median latest follow-up year 2020). We calculated age-adjusted and sex-adjusted hazard ratios (HRs) for all-cause mortality according to age at diagnosis of diabetes using data from 1 515 718 participants, in whom deaths were recorded during 23·1 million person-years of follow-up. We estimated cumulative survival by applying age-specific HRs to age-specific death rates from 2015 for the USA and the EU. Findings: For participants with diabetes, we observed a linear dose–response association between earlier age at diagnosis and higher risk of all-cause mortality compared with participants without diabetes. HRs were 2·69 (95% CI 2·43–2·97) when diagnosed at 30–39 years, 2·26 (2·08–2·45) at 40–49 years, 1·84 (1·72–1·97) at 50–59 years, 1·57 (1·47–1·67) at 60–69 years, and 1·39 (1·29–1·51) at 70 years and older. HRs per decade of earlier diagnosis were similar for men and women. Using death rates from the USA, a 50-year-old individual with diabetes died on average 14 years earlier when diagnosed aged 30 years, 10 years earlier when diagnosed aged 40 years, or 6 years earlier when diagnosed aged 50 years than an individual without diabetes. Using EU death rates, the corresponding estimates were 13, 9, or 5 years earlier. Interpretation: Every decade of earlier diagnosis of diabetes was associated with about 3–4 years of lower life expectancy, highlighting the need to develop and implement interventions that prevent or delay the onset of diabetes and to intensify the treatment of risk factors among young adults diagnosed with diabetes. Funding: British Heart Foundation, Medical Research Council, National Institute for Health and Care Research, and Health Data Research UK

High prevalence of diabetes and intermediate hyperglycemia – The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Background: The global burden of diabetes mellitus and other chronic diseases is high, and 80% of those with diabetes now live in low and middle income countries. Yet, little information is available regarding prevalence of diabetes and intermediate hyperglycemia in these countries, especially when a full range of diagnostic tests is employed. The purpose of this study is to provide a full accounting of these prevalences in a large, free-living Brazilian population. Methods: We report baseline data (2008-2010) from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a cohort study of 15,105 civil servants aged 35-74 years. Diabetes mellitus was ascertained by self-report of diagnosis, medication use, fasting glucose, an oral glucose tolerance test, and/or glycated hemoglobin. Cut-offs for diabetes and intermediate hyperglycemia followed the recommendations of the World Health Organization and the American Diabetes Association. Adjusted prevalences were estimated through logistic regression. Findings: With this full accounting, 19.7% (19.0%-20.3%) had diabetes mellitus, 50.4% being previously undiagnosed. Frequencies of intermediate hyperglycemia according to various criteria ranged from 16.1% to 52.6%. Diabetes or intermediate hyperglycemia was present in 79.1% of participants when using the most comprehensive definitions. The burden was greatest in the elderly, the obese, non-whites, and those with less formal education (p < 0.001). Interpretation: That four of every five free-living individuals aged 35-74 years working in selected public institutions in six Brazilian state capitals presented either diabetes or intermediate hyperglycemia highlights the advanced stage of the obesity – diabetes epidemic in urban Brazil and indicates the need for urgent action

Safety of intracoronary provocative testing for the diagnosis of coronary artery spasm.

AIMS: Systematic review of literature to evaluate safety of intracoronary (i.c.) pharmacologic testing with acetylcholine (ACh), or ergonovine (ERGO), to induce coronary artery spasm. METHODS AND RESULTS: Review of all relevant publications using MEDLINE and EMBASE databases yielded 10 publications, totalling 9,444 patients. Prevalence of provoked spasm varied from 2.3% to 54.7% of patients tested in the selected studies. The wide variability in prevalence was due to heterogeneity of study populations and provocation protocols. No deaths were reported. Overall occurrence of major (0.8%) and minor (4.7%) complications for i.c. pharmacologic testing was low. Compared to ERGO, ACh showed significantly higher rate of major (1.09% vs 0.15%; p<0.001) and minor complications (5.87% vs 2.36%; p<0.001). CONCLUSION: Provocative testing with i.c. ACh or ERGO are safe and can facilitate the diagnosis of inducible coronary artery spasm during diagnostic coronary angiography. These tests should be part of the routine armamentarium of interventional cardiologists

Investigation of cardiovascular health and risk factors among the diverse and contemporary population in London (the TOGETHER Study): protocol for linking longitudinal medical records

Background: Global trends in cardiovascular disease (CVD) exhibit considerable interregional and interethnic differences, which in turn affect long-term CVD risk across diverse populations. An in-depth understanding of the interplay between ethnicity, socioeconomic status, and CVD risk factors and mortality in a contemporaneous population is crucial to informing health policy and resource allocation aimed at mitigating long-term CVD risk. Generating bespoke large-scale and reliable data with sufficient numbers of events is expensive and time-consuming but can be circumvented through utilization and linkage of data routinely collected in electronic health records (EHR). Objective: We aimed to characterize the burden of CVD risk factors across different ethnicities, age groups, and socioeconomic groups, and study CVD incidence and mortality by EHR linkage in London. Methods: The proposed study will initially be a cross-sectional observational study unfolding into prospective CVD ascertainment through longitudinal follow-up involving linked data. The government-funded National Health System (NHS) Health Check program provides an opportunity for the systematic collation of CVD risk factors on a large scale. NHS Health Check data on approximately 200,000 individuals will be extracted from consenting general practices across London that use the Egton Medical Information Systems (EMIS) EHR software. Data will be analyzed using appropriate statistical techniques to (1) determine the cross-sectional burden of CVD risk factors and their prospective association with CVD outcomes, (2) validate existing prediction tools in diverse populations, and (3) develop bespoke risk prediction tools across diverse ethnic groups. Results: Enrollment began in January 2019 and is ongoing with initial results to be published mid-2021. Conclusions: There is an urgent need for more real-life population health studies based on analyses of routine health data available in EHRs. Findings from our study will help quantify, on a large scale, the contemporaneous burden of CVD risk factors by geography and ethnicity in a large multiethnic urban population. Such detailed understanding (especially interethnic and sociodemographic variations) of the burden of CVD risk and its determinants, including heredity, environment, diet, lifestyle, and socioeconomic factors, in a large population sample, will enable the development of tailored and dynamic (continuously learning from new data) risk prediction tools for diverse ethnic groups, and thereby enable the personalized provision of prevention strategies and care. We anticipate that this systematic approach of linking routinely collected data from EHRs to study CVD can be conducted in other settings as EHRs are being implemented worldwide. International Registered Report Identifier (IRRID): PRR1-10.2196/17548 JMIR Res Protoc 2020;9(10):e1754

Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials

Background: Whether intensive control of glucose reduces macrovascular events and all-cause mortality in individuals with type 2 diabetes mellitus is unclear. We undertook a meta-analysis of randomised controlled trials to determine whether intensive treatment is beneficial. Methods: We selected five prospective randomised controlled trials of 33 040 participants to assess the effect of an intensive glucose-lowering regimen on death and cardiovascular outcomes compared with a standard regimen. We gathered information about events of non-fatal myocardial infarction, coronary heart disease (fatal and non-fatal myocardial infarction), stroke, and all-cause mortality, and did a random-effects meta-analysis to obtain summary effect estimates for the clinical outcomes with use of odds ratios calculated from the raw data of every trial. Statistical heterogeneity across trials was assessed with the χ2 and I2 statistics. Findings: The five trials provided information on 1497 events of non-fatal myocardial infarction, 2318 of coronary heart disease, 1127 of stroke, and 2892 of all-cause mortality during about 163 000 person-years of follow-up. The mean haemoglobin A1c concentration (HbA1c) was 0·9% lower for participants given intensive treatment than for those given standard treatment. Intensive glycaemic control resulted in a 17% reduction in events of non-fatal myocardial infarction (odds ratio 0·83, 95% CI 0·75–0·93), and a 15% reduction in events of coronary heart disease (0·85, 0·77–0·93). Intensive glycaemic control had no significant effect on events of stroke (0·93, 0·81–1·06) or all-cause mortality (1·02, 0·87–1·19). Interpretation: Overall, intensive compared with standard glycaemic control significantly reduces coronary events without an increased risk of death. However, the optimum mechanism, speed, and extent of HbA1c reduction might be different in differing populations

Estimating the economic burden of cardiovascular events in patients receiving lipid-modifying therapy in the UK.

Objectives To characterise the costs to the UK National Health Service of cardiovascular (CV) events among individuals receiving lipid-modifying therapy. Design Retrospective cohort study using Clinical Practice Research Datalink records from 2006 to 2012 to identify individuals with their first and second CVrelated hospitalisations (first event and second event cohorts). Within-person differences were used to estimate CV-related outcomes. Setting Patients in the UK who had their first CV event between January 2006 and March 2012. Participants Patients ≥18 years who had a CV event and received at least 2 lipid-modifying therapy prescriptions within 180 days beforehand. Primary and secondary outcome measures Direct medical costs (2014 £) were estimated in 3 periods: baseline (pre-event), acute (6 months afterwards) and long-term (subsequent 30 months). Primary outcomes included incremental costs, resource usage and total costs per period. Results There were 24 093 patients in the first event cohort of whom 5274 were included in the second event cohort. The mean incremental acute CV event costs for the first event and second event cohorts were: coronary artery bypass graft/percutaneous transluminal coronary angioplasty (CABG/PTCA) £5635 and £5823, myocardial infarction £4275 and £4301, ischaemic stroke £3512 and £4572, heart failure £2444 and £3461, unstable angina £2179 and £2489 and transient ischaemic attack £1537 and £1814. The mean incremental long-term costs were: heart failure £848 and £2829, myocardial infarction £922 and £1385, ischaemic stroke £973 and £682, transient ischaemic attack £705 and £1692, unstable angina £328 and £677, and CABG/PTCA £−368 and £599. Hospitalisation accounted for 95% of acute and 61% of long-term incremental costs. Higher comorbidity was associated with higher long-term costs. Conclusions Revascularisation and myocardial infarction were associated with the highest incremental costs following a CV event. On the basis of real-world data, the economic burden of CV events in the UK is substantial, particularly among those with greater comorbidity burden.</p