Identification and Mapping Real-World Data Sources for Heart Failure, Acute Coronary Syndrome, and Atrial Fibrillation.

BACKGROUND: Transparent and robust real-world evidence sources are increasingly important for global health, including cardiovascular (CV) diseases. We aimed to identify global real-world data (RWD) sources for heart failure (HF), acute coronary syndrome (ACS), and atrial fibrillation (AF). METHODS: We conducted a systematic review of publications with RWD pertaining to HF, ACS, and AF (2010-2018), generating a list of unique data sources. Metadata were extracted based on the source type (e.g., electronic health records, genomics, and clinical data), study design, population size, clinical characteristics, follow-up duration, outcomes, and assessment of data availability for future studies and linkage. RESULTS: Overall, 11,889 publications were retrieved for HF, 10,729 for ACS, and 6,262 for AF. From these, 322 (HF), 287 (ACS), and 220 (AF) data sources were selected for detailed review. The majority of data sources had near complete data on demographic variables (HF: 94%, ACS: 99%, and AF: 100%) and considerable data on comorbidities (HF: 77%, ACS: 93%, and AF: 97%). The least reported data categories were drug codes (HF, ACS, and AF: 10%) and caregiver involvement (HF: 6%, ACS: 1%, and AF: 1%). Only a minority of data sources provided information on access to data for other researchers (11%) or whether data could be linked to other data sources to maximize clinical impact (20%). The list and metadata for the RWD sources are publicly available at www.escardio.org/bigdata. CONCLUSIONS: This review has created a comprehensive resource of CV data sources, providing new avenues to improve future real-world research and to achieve better patient outcomes.

Real-world treatment patterns of sacubitril/valsartan: a longitudinal cohort study in Germany.

AIMS: To analyse real-world treatment patterns of sacubitril/valsartan (sac/val) using data from a pharmacy database in Germany. METHODS AND RESULTS: A retrospective cohort study of 26 191 adult patients (aged ≥ 18 years) in the IMS® longitudinal prescriptions database in Germany who were dispensed sac/val from January 2016 to June 2017 was conducted. The analysis included sac/val dose titration assessed in the 6 months from first sac/val prescription; prescriptions of concomitant cardiovascular medications in the 6 months pre- and post-index and compliance and persistence during 12 months post-index. Two-thirds of patients were prescribed the lowest sac/val dose of 50 mg twice daily (b.i.d.) at index and up-titration during the first 6 months was attempted in 41% of these patients. Ten percent of patients prescribed 200 mg b.i.d. at index had to be stably down-titrated; among patients prescribed 50 or 100 mg b.i.d. at index that were up-titrated, > 80% remained on the higher dose. Overall, the mean daily diuretic dose decreased by 25% after initiation of sac/val. High compliance and persistence rates were observed across sac/val doses, increasing with higher sac/val dose at index. Prior dose of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker had only minor impact on first sac/val dose, compliance and persistence. CONCLUSIONS: Most patients prescribed sac/val are not initiated on the recommended dose nor up-titrated as recommended by the EU Summary of Product Characteristics. Initiation of sac/val was associated with high persistence and compliance and a dose reduction of diuretics. Barriers to up-titration must be explored.

Heart failure in Finland: clinical characteristics, mortality, and healthcare resource use.

AIMS: The aims of this study were to describe patient characteristics of the adult chronic heart failure (HF) population and to estimate the prevalence, incidence, healthcare resource utilization (HCRU), and mortality associated with HF in Southwest Finland. METHODS AND RESULTS: This was a retrospective biobank and clinical registry study. Adult patients with an HF diagnosis (International Statistical Classification of Diseases and Related Health Problems (ICD) code I50) during 2004-2013 in secondary care were included in the study and compared with age-matched and gender-matched control patients without an I50 diagnosis. HF patients were stratified in groups by left ventricular ejection fraction (LVEF) as follows: LVEF < 40% [HF with reduced ejection fraction (HFrEF)]; LVEF ≥ 40% [HF with preserved ejection fraction (HFpEF)]; or unknown (LVEF unknown). HCRU was stratified by inpatient, outpatient, and emergency room visits. In 2013, the incidence of HF was 3.2/1000, and the prevalence was 13.9/1000 inhabitants (n = 15 594). In the stratified analysis of HF patients (n = 8833, average ± SD age 77.1 ± 11.2), 1115 (12.6%) patients had HFrEF (female 31.3%), 1449 (16.4%) had HFpEF (female 50.9%), and 6269 (71%) had unknown LVEF (female 52.1%). The most common co-morbidities were essential hypertension (58%), chronic elevated serum creatinine (57.3%), atrial fibrillation and flutter (55.1%), and chronic ischaemic heart disease (46.4%). Patients with HF diagnosis had higher HCRU compared with that of age-matched and gender-matched controls (3.7 more days per year at the hospital for HF patients compared with the controls). The total 5 year mortality was 62.6% for HF patients and 28.3% for controls, with higher age being the strongest predictor of mortality. Moreover, multivariable Cox regression analysis showed that patients with HFrEF had a 13% (95% confidence interval 2.7-25%) increased risk of mortality compared with HFpEF patients. CONCLUSIONS: The high mortality rate and HCRU among the studied HF patients highlight the severity of the disease and the economic and social burden on both patients and society. This calls for improved methods of care for this large patient population.

Perceptions of heart failure symptoms, disease severity, treatment decision-making, and side effects by patients and cardiologists: a multinational survey in a cardiology setting.

PURPOSE: Explore the extent to which heart failure (HF) symptoms and side effects of HF treatment experienced by patients are recognized by cardiologists, and concordance between patient-cardiologist perceptions of HF severity and patients' contributions to treatment decision-making. METHODS: A multinational, cross-sectional survey of cardiologists and patients with HF was conducted. Patient-record forms (PRFs) were completed by cardiologists for consecutive consulting patients with HF, who completed a patient self-completion questionnaire (PSC). Responses from PRFs with an associated PSC were analyzed to compare patient- and cardiologist-reported occurrences of HF symptoms and treatment side effects, patient-perceived severity of HF and cardiologists' perceived risk of death within 12 months, and patient input into treatment decisions. Concordance was calculated as the number of response agreements between PSCs and PRFs for total number of matched pairs. Over- or underreporting of symptoms and side effects by cardiologists relative to patient-reported occurrences were calculated. RESULTS: Overall, 2,454 patient-cardiologist pairs were identified. High levels of concordance between matched pairs were observed for the occurrence of reported HF symptoms (93%), side effects (77%-98%) and degree of patient input into treatment decisions (74%); for perceived HF severity, concordance was 54%. Most symptoms (except dyspnea when active and fatigue/weakness, experienced by >50% of patients) were underreported by cardiologists. Of patients reporting to have been informed by their cardiologist that their HF was mild, 28% were perceived by their cardiologist to have a moderate-high/very high risk of death within 12 months. Treatment choice was not discussed with almost a third of patients. When discussed, 94% of patients (n=1,540) reported the cardiologist made the final decision. Cardiologists more often under- than overreported the occurrence of side effects reported by patients. CONCLUSION: Improved patient-cardiologist dialogue and shared decision-making is required for optimizing patient care and outcomes in HF.

Glucagon-like Peptide-1 receptor agonist treatment patterns among type 2 diabetes patients in six European countries.

INTRODUCTION: The objective of this study was to evaluate real-world treatment patterns of type 2 diabetes (T2D) patients initiating glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in Germany (GE), the United Kingdom (UK), France (FR), the Netherlands (NE), Belgium (BE), and Sweden (SE). METHODS: Adult T2D patients initiating exenatide twice daily (exBID), liraglutide once daily (LIRA) or exenatide once weekly (exQW) were identified using the IMS LifeLink™ (IMS Health, Danbury, CT, USA): Electronic Medical Records (EMR; GE/UK/FR) and IMS LifeLink™: longitudinal prescriptions (LRx; NE/BE/GE/UK) databases, and national health register data (SE), between 2010 and 2012. Therapy initiation date was termed 'index date'. Eligible patients had ≥180-day pre- and variable follow-up (minimum ≥360-day post-index exBID and LIRA, ≥180-day post-index exQW). Treatment modification and persistence were evaluated over 180 days. Kaplan-Meier (KM) survival curves and Cox proportional hazards models (PHMs; EMR databases only) evaluated stopping of the index therapy (measured as first of discontinuation or switch). RESULTS: 30,206 exBID, 5,401 exQW, and 52,155 LIRA patients were included in the analysis (46.0-66.9% male; mean age range 55.4-59.3 years). Mean follow-up was 20.3-27.4 months for exBID and LIRA, and 7.6-13.9 months for exQW. Across the databases, the proportion experiencing a treatment modification at 180 days was highest among exBID (37.6-81.7%) compared to LIRA (36.8-56.6%) and exQW (32.3-47.7%). The proportion persistent at 180 days was lowest among exBID patients (46.8-73.5%) compared to LIRA (50.6-80.1%) or exQW (57.5-74.6%). In the KM analyses, LIRA patients had a lower proportion stopping therapy at all time points compared to exBID patients, across the databases. In the Cox PHMs, LIRA was associated with a significantly lower risk of stopping compared to exBID; in GE, exQW was associated with a lower risk compared to exBID and LIRA. CONCLUSION: Treatment patterns varied among GLP-1 RA patients, with persistence highest among either LIRA or exQW across countries, and lowest among exBID. Longer-term data would be useful, particularly given limited exQW follow-up due to more recent launch.

Altered Methylation of IGF2 Locus 20 Years after Preterm Birth at Very Low Birth Weight.

INTRODUCTION: People born preterm at very low birth weight (VLBW, ≤1500g) have higher rates of risk factors for adult-onset diseases, including cardiovascular diseases and type 2 diabetes. These risks may be mediated through epigenetic modification of genes that are critical to normal growth and development. METHODS: We measured the methylation level of an imprinted insulin-like-growth-factor 2 (IGF2) locus (IGF2/H19) in young adults born preterm at VLBW and in their peers born at term. We studied 158 VLBW and 161 control subjects aged 18 to 27 years from the Helsinki Study of Very Low Birth Weight Adults. Methylation fraction at two IGF2 differentially methylated regions (DMRs) - IGF2 antisense transcript (IGF2AS, also known as IGF2 DMR0) and last exon of IGF2 (IGF2_05, also known as IGF2 DMR2) - were measured with Sequenom Epityper. We used linear regression and adjustment for covariates to compare methylation fractions at these DMRs between VLBW and control subjects. RESULTS: At one IGF2AS CpG site, methylation was significantly lower in VLBW than in control subjects, mean difference -0.017 (95% CI; -0.028, -0.005), P = 0.004. Methylation at IGF2_05 was not different between the groups. CONCLUSIONS: Methylation of IGF2AS is altered 20 years after preterm birth at VLBW. Altered methylation may be a mechanism of later increased disease risk but more data are needed to indicate causality.