Mortality, Outcomes, Costs, and Use of Medicines Following a First Heart Failure Hospitalization: EVOLUTION HF.

BACKGROUND: There are few contemporary data on outcomes, costs, and treatment following a hospitalization for heart failure (hHF) in epidemiologically representative cohorts. OBJECTIVES: This study sought to describe rehospitalizations, hospitalization costs, use of guideline-directed medical therapy (GDMT) (renin-angiotensin system inhibitors, sacubitril/valsartan, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors), and mortality after hHF. METHODS: EVOLUTION HF (Utilization of Dapagliflozin and Other Guideline Directed Medical Therapies in Heart Failure Patients: A Multinational Observational Study Based on Secondary Data) is an observational, longitudinal cohort study using data from electronic health records or claims data sources in Japan, Sweden, the United Kingdom, and the United States. Adults with a first hHF discharge between 2018 and 2022 were included. The 1-year event rates per 100 patient-years (ERs) for death and rehospitalizations (with a primary diagnosis of heart failure (HF), chronic kidney disease [CKD], myocardial infarction, stroke, or peripheral artery disease) were calculated. Hospital health care costs were cumulatively summarized. Cumulative GDMT use was assessed using Kaplan-Meier estimates. RESULTS: Of 263,525 patients, 28% died within the first year post-hHF (ER: 28.4 [95% CI: 27.0-29.9]). Rehospitalizations were mainly driven by HF (ER: 13.6 [95% CI: 9.8-17.4]) and CKD (ER: 4.5 [95% CI: 3.6-5.3]), whereas the ERs for myocardial infarction, stroke, and peripheral artery disease were lower. Health care costs were predominantly driven by HF and CKD. Between 2020 and 2022, use of renin-angiotensin system inhibitors, sacubitril/valsartan, beta-blockers, and mineralocorticoid receptor antagonists changed little, whereas uptake of sodium-glucose cotransporter-2 inhibitors increased 2- to 7-fold. CONCLUSIONS: Incident post-hHF rehospitalization risks and costs were high, and GDMT use changed little in the year following discharge, highlighting the need to consider earlier and greater implementation of GDMT to manage risks and reduce costs.

Benefit Versus Risk Assessment of Melflufen and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Analyses From Longer Follow-up of the OCEAN and HORIZON Studies.

INTRODUCTION: Melphalan flufenamide (melflufen), a first-in-class alkylating peptide-drug conjugate, plus dexamethasone demonstrated superior progression-free survival (PFS) but directionally different overall survival (OS) favoring pomalidomide (hazard ratio [HR], 1.10) in OCEAN. METHODS: These analyses further investigated prognostic subgroups impacting survival in updated data from the randomized, phase 3 OCEAN study (NCT03151811; date: February 3, 2022) and the phase 2 HORIZON study (NCT02963493; date: February 2, 2022). RESULTS: In OCEAN, subgroups prognostic for OS were age (P = .011; <65 years favored pomalidomide) and no previous autologous stem cell transplant (ASCT) or progression >36 months after ASCT (P = .001; favored melflufen). Overall, 245 of 495 (49%) patients randomized had received a previous ASCT, of which 202 (82%) had progressed within 36 months following their ASCT. When excluding patients who had progressed <36 months post-ASCT (melflufen group, n = 145; pomalidomide group, n = 148), median OS was 23.6 months with melflufen and 19.8 months with pomalidomide (HR, 0.83 [95% CI, 0.62-1.12]; P = .22). Among patients with triple-class refractory disease in HORIZON, patients who had progressed <36 months post-ASCT (n = 58) had a lower response rate and shorter duration of response and PFS than the remaining patients (n = 52). Safety was consistent with previous reports. CONCLUSION: These analyses demonstrate a consistent benefit for melflufen and dexamethasone in patients with relapsed/refractory multiple myeloma who have not received an ASCT or progressed >36 months after receiving an ASCT (ClinicalTrials.gov identifier: NCT03151811).

Prevalence, outcomes and costs of a contemporary, multinational population with heart failure.

OBJECTIVE: Digital healthcare systems could provide insights into the global prevalence of heart failure (HF). We designed the CardioRenal and Metabolic disease (CaReMe) HF study to estimate the prevalence, key clinical adverse outcomes and costs of HF across 11 countries. METHODS: Individual level data from a contemporary cohort of 6 29 624 patients with diagnosed HF was obtained from digital healthcare systems in participating countries using a prespecified, common study plan, and summarised using a random effects meta-analysis. A broad definition of HF (any registered HF diagnosis) and a strict definition (history of hospitalisation for HF) were used. Event rates were reported per 100 patient years. Cumulative hospital care costs per patient were calculated for a period of up to 5 years. RESULTS: The prevalence of HF was 2.01% (95% CI 1.65 to 2.36) and 1.05% (0.85 to 1.25) according to the broad and strict definitions, respectively. In patients with HF (broad definition), mean age was 75.2 years (95% CI 74.0 to 76.4), 48.8% (40.9-56.8%) had ischaemic heart disease and 34.5% (29.4-39.6%) had diabetes. In 51 442 patients with a recorded ejection fraction (EF), 39.1% (30.3-47.8%) had a reduced, 18.8% (13.5-24.0%) had a mildly reduced and 42.1% (31.5-52.8%) had a preserved left ventricular EF. In 1 69 518 patients with recorded estimated glomerular filtration rate, 49% had chronic kidney disease (CKD) stages III-V. Event rates were highest for cardiorenal disease (HF or CKD) and all cause mortality (19.3 (95% CI 11.3 to 27.1) and 13.1 (11.1 to 15.1), respectively), and lower for myocardial infarction, stroke and peripheral artery disease. Hospital care costs were highest for cardiorenal diseases. CONCLUSIONS: We estimate that 1-2% of the contemporary adult population has HF. These individuals are at significant risk of adverse outcomes and associated costs, predominantly driven by hospitalisations for HF or CKD. There is considerable public health potential in understanding the contemporary burden of HF and the importance of optimising its management.

Prevalence, outcomes, and cost of chronic kidney disease in a contemporary population of 2·4 million patients from 11 countries: The CaReMe CKD study.

Background: Digital healthcare systems data could provide insights into the global prevalence of chronic kidney disease (CKD). We designed the CaReMe CKD study to estimate the prevalence, key clinical adverse outcomes and costs of CKD across 11 countries. Methods: Individual-level data of a cohort of 2·4 million contemporaneous CKD patients was obtained from digital healthcare systems in participating countries using a pre-specified common protocol; summarized using random effects meta-analysis. CKD and its stages were defined in accordance with current Kidney Disease: Improving Global Outcomes (KDIGO) criteria. CKD was defined by laboratory values or by a diagnosis code. Findings: The pooled prevalence of possible CKD was 10·0% (95% confidence interval 8.5‒11.4; mean pooled age 75, 53% women, 38% diabetes, 60% using renin-angiotensin-aldosterone system inhibitors). Two out of three CKD patients identified by laboratory criteria did not have a corresponding CKD-specific diagnostic code. Among CKD patients identified by laboratory values, the majority (42%) were in KDIGO stage 3A; and this fraction was fairly consistent across countries. The share with CKD based on urine albumin-creatinine ratio (UACR) alone (KDIGO stages one and two) was 29%, with a substantial heterogeneity between countries. Adverse events were common; 6·5% were hospitalized for CKD or heart failure, and 6·2% died, annually. Costs for renal events and heart failure were consistently higher than costs for atherosclerotic events in CKD patients across all countries. Interpretation: We estimate that CKD is present in one out of ten adults. These individuals experience significant adverse outcomes with associated costs. The prevalence of CKD is underestimated when using diagnostic codes alone. There is considerable public health potential in diagnosing CKD and providing treatments to those currently undiagnosed. Funding: The study was sponsored by AstraZeneca.

Cost of healthcare utilization associated with incident cardiovascular and renal disease in individuals with type 2 diabetes: A multinational, observational study across 12 countries.

AIM: To examine how the development of cardiovascular and renal disease (CVRD) translates to hospital healthcare costs in individuals with type 2 diabetes (T2D) initially free from CVRD. METHODS: Data were obtained from the digital healthcare systems of 12 nations using a prespecified protocol. A fixed country-specific index date of 1 January was chosen to secure sufficient cohort disease history and maximal follow-up, varying between each nation from 2006 to 2017. At index, all individuals were free from any diagnoses of CVRD (including heart failure [HF], chronic kidney disease [CKD], coronary ischaemic disease, stroke, myocardial infarction [MI], or peripheral artery disease [PAD]). Outcomes during follow-up were hospital visits for CKD, HF, MI, stroke, and PAD. Hospital healthcare costs obtained from six countries, representing 68% of the total study population, were cumulatively summarized for CVRD events occurring during follow-up. RESULTS: In total, 1.2 million CVRD-free individuals with T2D were identified and followed for 4.5 years (mean), that is, 4.9 million patient-years. The proportion of individuals indexed before 2010 was 18% (n = 207 137); 2010-2015, 31% (361 175); and after 2015, 52% (609 095). Overall, 184 420 (15.7%) developed CVRD, of which cardiorenal disease was most frequently the first disease to develop (59.7%), consisting of 23.0% HF and 36.7% CKD, and more common than stroke (16.9%), MI (13.7%), and PAD (9.7%). The total cumulative cost for CVRD was US$1 billion, of which 59.0% was attributed to cardiorenal disease, 3-, 5-, and 6-fold times greater than the costs for stroke, MI, and PAD, respectively. CONCLUSION: Across all nations, HF or CKD was the most frequent CVRD manifestation to develop in a low-risk population with T2D, accounting for the highest proportion of hospital healthcare costs. These novel findings highlight the importance of cardiorenal awareness when planning healthcare.

Cardiovascular and Renal Disease Burden in Type 1 Compared With Type 2 Diabetes: A Two-Country Nationwide Observational Study.

OBJECTIVE: Type 1 diabetes (T1D) and type 2 diabetes (T2D) increase risks of cardiovascular (CV) and renal disease (CVRD) compared with diabetes-free populations. Direct comparisons between T1D and T2D are scarce. We examined this by pooling full-population cohorts in Sweden and Norway. RESEARCH DESIGN AND METHODS: A total of 59,331 patients with T1D and 484,241 patients with T2D, aged 18-84 years, were followed over a mean period of 2.6 years from 31 December 2013. Patients were identified in nationwide prescribed drug and hospital registries in Norway and Sweden. Prevalence and event rates of myocardial infarction (MI), heart failure (HF), stroke, chronic kidney disease (CKD), all-cause death, and CV death were assessed following age stratification in 5-year intervals. Cox regression analyses were used to estimate risk. RESULTS: The prevalence of CV disease was similar in T1D and T2D across age strata, whereas CKD was more common in T1D. Age-adjusted event rates comparing T1D versus T2D showed that HF risk was increased between ages 65 and 79 years, MI between 55 and 79 years, and stroke between 40 and 54 years (1.3-1.4-fold, 1.3-1.8-fold, and 1.4-1.7-fold, respectively). CKD risk was 1.4-3.0-fold higher in T1D at all ages. The all-cause death risk was 1.2-1.5-fold higher in T1D at age >50 years, with a similar trend for CV death. CONCLUSIONS: Adult patients with T1D compared with those with T2D had an overall greater risk of cardiorenal disease (HF and CKD) across ages, MI and all-cause death at middle-older ages, and stroke at younger ages. The total age-adjusted CVRD burden and risks were greater among patients with T1D compared with those with T2D, highlighting their need for improved prevention strategies.

Assessing the cost-effectiveness of sodium-glucose cotransporter-2 inhibitors in type 2 diabetes mellitus: A comprehensive economic evaluation using clinical trial and real-world evidence.

AIMS: The economic burden of diabetes is driven by the management of vascular complications. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated reductions in cardiovascular and renal complications, including hospitalization for heart failure (HHF) and renal disease progression, in randomized clinical trials. The objective of this study was to evaluate the cost-effectiveness of the SGLT2i class versus standard of care in type 2 diabetes mellitus (T2DM), using evidence from both clinical trial and real-world studies. METHODS: An established T2DM model was adapted to use contemporary outcomes evidence from real-world studies and randomized controlled trial evaluations of SGLT2i, and extrapolated over a lifetime for HHF, myocardial infarction, stroke, end-stage renal disease and all-cause mortality. The economic analysis considered adults with T2DM, with and without established cardiovascular disease, and was conducted over a lifetime from the perspective of the health care payer in the United Kingdom, United States and China, discounted at country-specific rates. RESULTS: SGLT2i were consistently associated with increased treatment costs, reduced complication costs and gains in quality-adjusted life years driven by differences in projected life expectancy, cardiovascular and microvascular morbidity and weight loss. SGLT2i were estimated to be cost-saving or cost-effective at relevant thresholds for the overall population in the United Kingdom, United States and China, with cost-effectiveness being the greatest in higher risk subgroups. CONCLUSIONS: The findings highlight the need to take into account cost savings from reducing common, morbid and preventable T2DM complications when considering the cost of diabetes medications.

Dapagliflozin vs non-SGLT-2i treatment is associated with lower healthcare costs in type 2 diabetes patients similar to participants in the DECLARE-TIMI 58 trial: A nationwide observational study.

AIMS: To investigate how the cardiovascular (CV) risk benefits of dapagliflozin translate into healthcare costs compared with other non-sodium-glucose cotransporter-2 inhibitor glucose-lowering drugs (oGLDs) in a real-world population with type 2 diabetes (T2D) that is similar to the population of the DECLARE-TIMI 58 trial. METHODS: Patients initiating dapagliflozin or oGLDs between 2013 and 2016 in Swedish nationwide healthcare registries were included if they fulfilled inclusion and exclusion criteria of the DECLARE-TIMI 58 trial (DECLARE-like population). Propensity scores for the likelihood of dapagliflozin initiation were calculated, followed by 1:3 matching with initiators of oGLDs. Per-patient cumulative costs for hospital healthcare (in- and outpatient) and for drugs were calculated from new initiation until end of follow-up. RESULTS: A total of 24 828 patients initiated a new GLD; 6207 initiated dapagliflozin and 18 621 initiated an oGLD. After matching based on 96 clinical and healthcare cost variables, groups were balanced at baseline. Mean cumulative 30-month healthcare cost per patient was similar in the dapagliflozin and oGLD groups ($11 807 and $11 906, respectively; difference, -$99; 95% CI, -$629, $483; P = 0.644). Initiation of dapagliflozin rather than an oGLD was associated with significantly lower hospital costs (-$658; 95% CI, -$1169, -$108; P = 0.024) and significantly higher drug costs ($559; 95% CI, $471, $648; P < 0.001). Hospital cost difference was related mainly to fewer CV- and T2D-associated complications with use of dapagliflozin compared with use of an oGLD (-$363; 95% CI, -$665, -$61; P = 0.008). CONCLUSION: In a nationwide, real-world, DECLARE-like population, dapagliflozin was associated with lower hospital costs compared with an oGLD, mainly as a result of reduced rates of CV- and T2D-associated complications.

Health care resource utilization and cost for asthma patients regularly treated with oral corticosteroids - a Swedish observational cohort study (PACEHR).

BACKGROUND: Patients with severe uncontrolled asthma may receive oral corticosteroid (OCS) treatment regularly. The present study investigated the health care resource utilization and cost in regularly OCS treated Swedish asthma patients. METHODS: Primary care medical records data were linked to data from Swedish national health registries. Patients ≥18 years with a drug claim for obstructive pulmonary diseases during 2007-2009 (index date) and a prior asthma diagnosis, were classified by their OCS claims during the 12-months' post index period: regular OCS equals ≥5 mg per day; periodic OCS less than 5 mg per day; or non-OCS users. Cost of asthma- and OCS-morbidity-related health care resource utilization were calculated. RESULTS: A total of 15,437 asthma patients (mean age 47.8, female 62.6%), whereof 223 (1.44%) were regular OCS users, 3054 (19.7%) were periodic, and 12,160 (78.7%) were non-OCS users. Regular OCS users were older and more often females, had lower lung function, greater eosinophil count and more co-morbidities at baseline compared with the other groups. Age-adjusted annual total health care cost was three-times greater in the regular OCS group (€5615) compared with the non-OCS users (€1980) and twice as high as in the periodic OCS group (€2948). The major cost driver in the non-OCS and periodic OCS groups were primary care consultations, whereas inpatient costs were the major cost driver in the regular OCS group. The asthma related costs represented 10-12% of the total cost in all three groups. CONCLUSION: In this real-life asthma study in Sweden, the total yearly cost of health care resource utilization for a regular OCS user was three times greater than for a patient with no OCS use, indicating substantial economic and health care burden for asthma patients on regular oral steroid treatment.

Prevalence, characteristics and management of frequently exacerbating asthma patients: an observational study in Sweden (PACEHR).

The aim of the study was to investigate the prevalence, management and characteristics of asthma patients with frequent exacerbations.Data from asthma patients (aged ≥18 years) identified in primary care medical records were linked to Swedish national health registries. Exacerbations were defined as hospitalisations, emergency visits and/or collection of oral steroids. Frequent exacerbations were defined as two or more exacerbations per year during the 3-year observation period.Of 18 724 asthma patients, 81.49% had no exacerbations and 6.3% had frequent exacerbations in the year prior to the index date. Frequent exacerbations were observed yearly for 1.8% of the patients. Frequent exacerbators were older, more often females, and had increased eosinophil and neutrophil counts, lower lung function, and more comorbidities than patients without exacerbations. There was a slight increase in asthma medication claims and a slight decrease in physician visits compared with baseline, both in the group with and the group without frequent exacerbations.Patients with frequent exacerbations were characterised by greater age, female predominance, high eosinophil and neutrophil counts, and high prevalence of comorbidities. This study indicates that the Swedish healthcare system lacks efficiency to adjust treatment and management for this patient group. With new treatment options targeting severe asthma available, identification of these patients should be in focus to ensure reduction of exacerbations.

Rates of myocardial infarction and stroke in patients initiating treatment with SGLT2-inhibitors versus other glucose-lowering agents in real-world clinical practice: Results from the CVD-REAL study.

The multinational, observational CVD-REAL study recently showed that initiation of sodium-glucose co-transporter-2 inhibitors (SGLT-2i) was associated with significantly lower rates of death and heart failure vs other glucose-lowering drugs (oGLDs). This sub-analysis of the CVD-REAL study sought to determine the association between initiation of SGLT-2i vs oGLDs and rates of myocardial infarction (MI) and stroke. Medical records, claims and national registers from the USA, Sweden, Norway and Denmark were used to identify patients with T2D who newly initiated treatment with SGLT-2i (canagliflozin, dapagliflozin or empagliflozin) or oGLDs. A non-parsimonious propensity score was developed within each country to predict initiation of SGLT-2i, and patients were matched 1:1 in the treatment groups. Pooled hazard ratios (HRs) and 95% CIs were generated using Cox regression models. Overall, 205 160 patients were included. In the intent-to-treat analysis, over 188 551 and 188 678 person-years of follow-up (MI and stroke, respectively), there were 1077 MI and 968 stroke events. Initiation of SGLT-2i vs oGLD was associated with a modestly lower risk of MI and stroke (MI: HR, 0.85; 95%CI, 0.72-1.00; P = .05; Stroke: HR, 0.83; 95% CI, 0.71-0.97; P = .02). These findings complement the results of the cardiovascular outcomes trials, and offer additional reassurance with regard to the cardiovascular effects of SGLT-2i, specifically as it relates to ischaemic events.

Prevalence and management of severe asthma in primary care: an observational cohort study in Sweden (PACEHR).

BACKGROUND: Severe and uncontrolled asthma is associated with increased risk of exacerbations and death. A substantial proportion of asthma patients have poor asthma control, and a concurrent COPD diagnosis often increases disease burden. The objective of the study was to describe the prevalence and managemant of severe asthma in a Swedish asthma popuöation. METHODS: In this observational cohort study, primary care medical records data (2006-2013) from 36 primary health care centers were linked to data from national mandatory Swedish health registries. The studied population (>18 years) had a record of drug collection for obstructive pulmonary disease (ATC code R03) during 2011-2012, and a physician diagnosed asthma (ICD-10 code J45-J46) prior to drug collection. Severe asthma was classified as collection of high dose inhaled steroid (> 800 budesonide or equivalent per day) and leukotriene receptor antagonist and/or long-acting beta-agonist. Poor asthma control was defined as either collection of ≥600 doses of short-acting beta-agonists, and/or ≥1 exacerbation(s) during the year post index date. RESULTS: A total of 18,724 asthma patients (mean 49 years, 62.8% women) were included, of whom 17,934 (95.8%) had mild to moderate and 790 (4.2%) had severe asthma. Exacerbations were more prevalent in severe asthma (2.59 [2.41-2.79], Relative Risk [95% confidence interval]; p < 0.001). Poor asthma control was observed for 28.2% of the patients with mild to moderate asthma and for more than half (53.6%) of the patients with severe asthma (<0.001). Prior to index, one in five severe asthma patients had had a contact with secondary care and one third with primary care. A concurrent COPD diagnosis increased disease burden. CONCLUSION: Severe asthma was found in 4.2% of asthma patients in Sweden, more than half of them had poor asthma control, and most patients had no regular health care contacts.

Long-term cardiovascular outcome, use of resources, and healthcare costs in patients with peripheral artery disease: results from a nationwide Swedish study.

Aims: Data on long-term healthcare costs of patients with peripheral artery disease (PAD) is limited, and the aim of this study was to investigate healthcare costs for PAD patients at a nationwide level. Methods and results: A cohort study including all incident patients diagnosed with PAD in the Swedish National Patient Register between 2006-2014, and linked to cause of death- and prescribed drug registers. Mean per-patient annual healthcare costs (2015 Euros [€]) (hospitalisations and out-patient visits) were divided into cardiovascular (CV), lower limb and non-CV related cost. Results were stratified by high and low CV risk. The study included 66,189 patients, with 221,953 observation-years. Mean total healthcare costs were €6,577, of which 26% was CV-related (€1,710), during the year prior to the PAD diagnosis. First year after PAD diagnosis, healthcare costs were €12,549, of which €3,824 (30%) was CV-related and €3,201 (26%) lower limb related. High-risk CV patients had a higher annual total healthcare and CV related costs compared to low risk CV patients during follow-up (€7,439 and €1,442 versus €4,063 and €838). Annual lower limb procedure costs were €728 in the PAD population, with lower limb revascularisations as key cost driver (€474). Conclusion: Non-CV related hospitalizations and outpatient visits were the largest cost contributors for PAD patients. There is a substantial increase in healthcare costs in the first year after being diagnosed with PAD, driven by PAD follow-up and lower limb related procedures. Among the CV-related costs, hospitalisations and outpatient visits related to PAD represented the largest costs.

Long-term resource use patterns and healthcare costs after myocardial infarction in a clinical practice setting: results from a contemporary nationwide registry study.

Aims: Long-term contemporary nationwide data on resource use and healthcare costs after myocardial infarction (MI) in a clinical practice setting are not widely studied, and the aim of this study was to investigate resource use patterns and healthcare costs in patients with MI in a nationwide clinical practice setting. Methods and results: This retrospective cohort study included all patients identified in the compulsory Swedish nationwide patient register with a diagnosis of MI between 1 July 2006 and 30 June 2011. Cardiovascular hospitalization and outpatient visits data from the patient register were combined with data from the cause of death register and the drug utilization register. For a subset of patients, data were also available from a primary care register. Healthcare resource use patterns and annual costs [reported in 2014 euros (€) converted from Swedish kronor (SEK) using the exchange rate €1 = SEK 9.33)] were estimated for the year prior to the occurrence of MI as well as for a maximum follow-up period of 6 years post-MI. The study included 97 252 patients with a diagnosis of MI with a total number of 285 351 observation years. The majority of healthcare consumption occurred within the first year of MI where patients were on average hospitalized 1.55 times, made 1.08 outpatient care visits, and 3.80 primary care visits. In the long term, for the majority of resource use categories, average consumption was higher in the years after MI compared with the year prior to MI. Healthcare costs at 6 years of follow-up were approximately €20 000 of which €12 460 occurred in the first year, and the major part was attributed to hospitalizations. Conclusion: For patients with 6 years of follow-up after MI, healthcare costs were approximately €20 000. The major part of costs occurred in the first year after MI and was driven by hospitalizations. ClinicalTrials.gov identifier: NCT01984307.