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There are few contemporary data on outcomes, costs, and treatment following a hospitalization for heart failure (hHF) in epidemiologically representative cohorts.

ObjectiveDigital 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.MethodsIndividual 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.ResultsThe 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.ConclusionsWe 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.

Guidelines recommend early initiation of multiple guideline-directed medical therapies (GDMTs) to reduce mortality/rehospitalization in patients with heart failure and reduced ejection fraction. Understanding GDMT use is critical to improving clinical practice.

Cardiovascular outcome trials have shown cardiovascular benefit with sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors have not shown an effect. We aimed to address knowledge gaps regarding the comparative effectiveness of SGLT2 inhibitor use in clinical practice (with DPP-4 inhibitor use as an active comparator) across a range of cardiovascular risks and in diverse geographical settings.

Cardiovascular and kidney outcome trials have shown that sodium-glucose co-transporter-2 (SGLT2) inhibitors slow progression of chronic kidney disease in patients with type 2 diabetes with or without chronic kidney disease. The aim of this study was to assess whether these benefits extend to patients with type 2 diabetes treated in routine clinical practice.

Background/Introduction:Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases resulting in rapid release of alkylating agents inside tumor cells. Based on the phase 2 HORIZON study and supported by the phase 3, randomized, controlled OCEAN study, melflufen was approved in Europe for use in patients (pts) with triple-class refractory RRMM with ≥3 prior lines of therapy (LoTs) and without prior autologous stem cell transplantation (ASCT) or with a time to progression (TTP) >36 mo after prior ASCT. In the OCEAN study (NCT03151811), melflufen + dex showed superior progression-free survival (PFS) compared with pom + dex (6.8 vs 4.9 mo; hazard ratio [HR]: 0.79; P=0.032); PFS benefit in the melflufen + dex group was mainly driven by pts who had not received prior ASCT. Overall survival (OS) trended in favor of melflufen + dex in pts without prior ASCT and favored pom + dex in pts with prior ASCT (Schjesvold et al. Lancet Haematol. 2022;9:e98). Post-hoc analyses of OCEAN and HORIZON demonstrated that a TTP <36 mo after prior ASCT was a negative prognostic factor for OS with melflufen + dex (Sonneveld et al. Clin Lymphoma Myeloma Leuk. 2023;S2152). Here, we present long-term OS and safety data from the final analysis of the OCEAN study.

Background:In patients with relapsed/refractory multiple myeloma (RRMM), 29%-59% have high-risk (HR) cytogenetic abnormalities that are associated with poor treatment outcomes (Kumar et al. Leukemia.2017;31:2443; Gandhi et al. Leukemia.2019;33:2266). Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate (PDC) that targets aminopeptidases and rapidly releases alkylating agents into tumor cells. Melflufen plus dexamethasone (dex) showed clinically meaningful efficacy and a manageable safety profile in patients with heavily pretreated and poor-risk RRMM in the phase 2 HORIZON study (OP-106; NCT02963493; Richardson et al. EHA 2020. Abs. EP945). The overall response rate (ORR) was 29%, median progression-free survival (PFS) was 4.2 months, and median overall survival (OS) was 11.6 months. The most common nonhematologic grade 3/4 adverse event (AE) was pneumonia (10%). This is an analysis of the cytogenetic profile and a comparison of the efficacy for patients with and without HR cytogenetic abnormalities in the HORIZON study.

Background:EMD is characterized by a subclone of aggressive MM cells that thrive and grow independent of the bone marrow microenvironment and is often associated with poor-risk features including high-risk cytogenetics, increased proliferation, evasion of apoptosis, and resistance to therapies in MM (Bladé et al. J Clin Oncol. 2011;29:3805; Deng et al. Clin Lymphoma Myeloma Leuk.2015;15:286). Prognosis for pts with EMD is poor, particularly in the RRMM setting. Additionally, prognosis is usually poorer for pts with hematogenous-spread soft-tissue plasmacytomas than for those with bone-related plasmacytomas (Gagelmann et al. Haematologica.2018;103:890; Mangiacavalli et al. Ann Hematol. 2017;96:73). No standard therapy has been established for this high-unmet need population (Usmani et al. Blood.2016;128:37; Jimenez-Segura et al. Eur J Haematol.2019;102:389), and outcomes are considerably worse than those for pts without EMD; for example, a recent analysis of isatuximab + pomalidomide + dex showed a median progression free survival (PFS) of 4.6 mo vs 11.5 mo in the total population (Beksac et al. EHA 2020. Abs. EP978).

Background:Patients with RRMM receive multiple lines of therapy in their disease course and often become refractory to or are intolerant of newer approved therapies (eg, IMiDs, anti-CD38 monoclonal antibody [mAb] therapy, proteasome inhibitors [PIs]), limiting effective treatment options (Kumar et al. Leukemia.2017; 31:2443). Efficacy outcomes decrease with each line of therapy, showing a need for agents with novel mechanisms of action to improve treatment responses and survival outcomes (Gandhi et al. Leukemia.2019;33:2266).

Background:Advances in therapy have improved outcomes in multiple myeloma (MM), but enhancement in overall survival (OS) has resulted in patients living with the burden of symptoms and complications of relapsed/refractory MM (RRMM) and prior lines of therapy (Vogl et al. Leuk Lymphoma.2018;59:398; Kumar et al. Leukemia. 2017;31:2443). Elderly patients represent a particularly difficult-to-treat population with RRMM due to the additional presence of comorbidities, reduced fitness level, and treatment with concomitant medications (Larocca et al. Leukemia.2018;32:1697). There is an unmet need for efficacious and convenient treatment options with manageable side effects to optimize tolerability for elderly patients with RRMM. Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate (PDC) that targets aminopeptidases and rapidly releases alkylating agents into tumor cells. In the phase 2 HORIZON study (OP-106; NCT02963493), melflufen plus dexamethasone (dex) demonstrated encouraging efficacy and a clinically manageable safety profile in patients with heavily pretreated RRMM (Richardson et al. EHA 2020. Abs. EP945). This analysis examines the efficacy and safety of melflufen plus dex in the subset of patients aged ≥75 years in the HORIZON study.

Background:With advances in therapy, outcomes have generally improved for pts with MM; however, pts with late-stage RRMM have limited treatment options and poor outcomes (Kumar et al. Leukemia.2017;31:2443; Gandhi et al. Leukemia. 2019;33:2266). Pts with late-stage RRMM, often older and having comorbidities, require efficacious and tolerable therapies to maintain HRQoL (Richardson et al. Blood.2019;134[suppl 1]:3487).

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.

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In patients with type 2 diabetes and a high cardiovascular risk profile, the sodium-glucose co-transporter-2 (SGLT2) inhibitors empagliflozin and canagliflozin have been shown to lower cardiovascular morbidity and mortality. Using real-world data from clinical practice, we aimed to compare cardiovascular mortality and morbidity in new users of SGLT2 inhibitors versus new users of other glucose-lowering drugs, in a population with a broad cardiovascular risk profile.

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Introduction:In the period after hospitalization for heart failure (hHF), patients are at high risk of cardiovascular death and rehospitalization. Guidelines for heart failure with reduced ejection fraction (HFrEF) emphasize early initiation of four guideline-directed medical therapies (GDMTs: beta-blocker, renin-angiotensin system inhibitors [RASis] or angiotensin receptor neprilysin inhibitor, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter-2 inhibitors [SGLT2is]). However, real-world data on the concurrent use of these four GDMTs are scarce, particularly after hHF.Methods:EVOLUTION HF is an observational, longitudinal cohort study using claims and electronic health record databases to assess the use of GDMTs in patients with a recorded hHF. We report KM estimates of initiation of GDMTs in the 3 months following an incident hHF (index date) with no prior HF diagnosis. Use of GDMTs in the month before the index hHF (e.g. RASis for hypertension) was counted as use at index. The study period started after approval of the first SGLT2i (dapagliflozin) for HFrEF in each country.Results:Overall, 49 807 patients were included. Ejection fraction was not recorded for most patients. Mean KM estimates for use of four GDMTs at 1 and 3 months post hHF discharge were 6.5% and 7.8% (Japan), 8.0% and 11.7% (Sweden), and 0.9% and 1.7% (USA), increasing with each consecutive calendar quarter (Figure). This trend was largely explained by an increase in SGLT2i use. In the first and last quarter of each study period, KM estimates of SGLT2i use at 3 months were 15.3% and 21.2% (Japan), 7.2% and 32.6% (Sweden), and 2.3% and 4.8% (USA).Conclusions:Uptake of four GDMTs remains low, highlighting an urgent need for earlier and increased GDMT initiation to manage severe risks, especially in the vulnerable post-hHF period. Data on SGLT2i benefits have led to a slow yet steady increase in SGLT2i early use post hHF as part of a four-GDMT approach to treating HF.

Objectives:The objective of this work was to study characteristics and clinical treatment patterns of bipolar disorder (BD) patients admitted to hospital and treated with quetiapine (immediate-release [IR] or extended-release [XR] formulations).Methods:BD patients admitted to hospital and prescribed quetiapine IR were followed by linking two Swedish nationwide registries; the hospitalization and drug dispense registries [ClinicalTrials.gov identifier: NCT01455961]. The study period was from 1 January 2008, to end of 31 December 2011. Data was primarily analysed using descriptive methods.Results:Quetiapine IR was used in 1761 patients of whom 1303 subsequently switched to XR (switch XR) and 458 remained on IR (continuous IR). At baseline, Switch XR patients were younger (−3.3 years), more frequently employed (+7.1%), had higher prevalence of single depressive episodes (+6.7%) and anxiety disorders (+5.8%), lower mean daily IR dose (−19.3%) and fewer medications for somatic disorders (−7.5%) than continuous IR patients. During follow up, the number of concomitant psychiatric medications was lower in switch XR patients (−6%) and higher in continuous IR patients (+6%). Mean daily quetiapine dose was 21% higher in switch XR versus continuous IR patients. Prescriptions of lower quetiapine dosages calculated below 50 mg per day in the XR switch and IR continuous groups were seen in 8% versus 10% of the patients, respectively.Conclusions:Differential use of quetiapine XR and IR in bipolar disorder patients with different and important characteristics was demonstrated. Patients who were switched to quetiapine XR had a higher psychiatric disease burden, were younger and had a higher degree of employment. These differences demonstrate the heterogeneity among bipolar disorder patients and indicate the need in clinical practice for individualized treatment to reduce the risk for both patient and society related losses.

In this 24-month follow-up of a phase II study in patients with castration-resistant prostate cancer (CRPC) and bone metastases, radium-223 (4 injections of 50 kBq/kg every 4 weeks [n = 33]) improved median overall survival vs. matching placebo (n = 31) (65.3 vs. 46.4 weeks, respectively; log-rank P= .056), with no long-term safety concerns. Data suggest that treatment of bone disease with radium-223 has survival benefits.

The article focuses on the approach of most sports to change their rules and scoring systems in an effort to improve the quality of their sport in Europe. The authors lay out an argument in defense of the two points for a win system, as opposed to the old three points in the European soccer leagues. They reveal that the old system would have resulted in fairly qualifying better regional teams for the European cup competition.

Melphalan flufenamide (melflufen), an alkylating peptide-drug conjugate, plus dexamethasone showed clinical activity and manageable safety in the phase 2 HORIZON study. We aimed to determine whether melflufen plus dexamethasone would provide a progression-free survival benefit compared with pomalidomide plus dexamethasone in patients with previously treated multiple myeloma.

Background:Current treatments for MM consist of multidrug regimens combining a variety of drug classes including IMiDs, proteasome inhibitors (PIs), monoclonal antibodies (mAbs), alkylators, XP01 inhibitors, histone deacetylase inhibitors, and corticosteroids. Despite advances in therapy, outcomes remain poor for pts with RRMM. Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate (PDC) that targets aminopeptidases and rapidly releases alkylating agents into tumor cells. In the pivotal, phase 2 HORIZON study (NCT02963493), melflufen plus dex showed meaningful efficacy and a safety profile characterized primarily by clinically manageable hematologic adverse events (AEs) in heavily pretreated and poor-risk pts with RRMM (Richardson et al. EHA 2020. Abs. EP945). Preclinical data show that melflufen is 50-fold more potent than melphalan against MM cells due to an increased intracellular alkylator concentration (Wickstrom et al. Oncotarget.2017;8:666641). Melflufen has a mechanism of action distinct from alkylators, with cytotoxicity independent of p53 activity (Slipicevic et al. AACR 2020. Abs. 1843). In this analysis, the clinical activity of melflufen is examined in a subset of pts exposed to prior alkylator therapy.

Background:Older patients (pts) with relapsed/refractory multiple myeloma (RRMM) represent a particularly difficult-to-treat population due to comorbidities, frailty or reduced fitness level, and treatment with concomitant medications (Larocca et al. Leukemia.2018;32:1697); further, pts may have limited therapeutic options due to ineligibility to receive more intensive treatments (eg, autologous stem cell transplant [ASCT]). Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases and thereby rapidly releases alkylating agents into tumor cells. Melflufen + dexamethasone (dex) showed clinically meaningful efficacy and a manageable safety profile in pts with heavily pretreated RRMM in the phase 2 HORIZON study (OP-106; NCT02963493; Richardson et al. J Clin Oncol.2021;39:757), which led to its accelerated approval in the United States. In the phase 3 OCEAN study (OP-103; NCT03151811; Oncopeptides. Press release. July 8, 2021), a head-to-head comparison of melflufen + dex and pomalidomide (pom) + dex showed superiority of melflufen (vs pom) with a 39% longer median progression-free survival (PFS) (HR, 0.79 [95% CI, 0.64-0.98], P=0.0311), but no clear overall survival (OS) benefit. This analysis compares the efficacy between pts in the melflufen arm vs pom arm based on age and prior ASCT in the OCEAN study.

Background:Most pts with MM are older (median age at diagnosis: 69 y), have comorbidities (Engelhardt, et al. Haematologica.2017;102:910), and often relapse. Thus, there is a high unmet need for novel, tolerable agents to treat RRMM. Melphalan flufenamide (melflufen)-a first-in-class alkylating peptide-drug conjugate targeting aminopeptidases-and dex received accelerated approval for use in RRMM in the United States based on the phase 2 HORIZON study results (Richardson, et al. J Clin Oncol. 2021;39:757). Melflufen + dex was superior to pom + dex in pts with RRMM based on the primary endpoint of progression-free survival (hazard ratio [HR], 0.79 [95% CI, 0.64-0.98]; P=.0311), but showed no overall survival benefit (HR, 1.10 [95% CI, 0.85-1.44]) in the phase 3 randomized OCEAN study (NCT03151811; Oncopeptides. Press release. Jul 8, 2021). This abstract reports the first high-level safety and tolerability data from OCEAN.

Background:Despite the expansion of effective treatment options for multiple myeloma (MM), the disease regularly relapses and the majority still die from the disease (Kumar et al. Leukemia.2017;31:2443). RI is a common comorbidity in patients (pts) with MM, occurring in up to 50% of pts, and is associated with poor survival outcomes (Dimopoulos, et al. J Clin Oncol. 2016;34:1544).

Background:Most pts with MM will be exposed to alkylators throughout their disease course as part of a multidrug regimen or as high-dose melphalan (HDM) conditioning prior to undergoing an autologous stem cell transplant (SCT). MM invariably relapses and can become refractory to prior treatments. Outcomes are poor for pts with RRMM, highlighting the need for effective agents with novel mechanisms of action (Kumar et al. Leukemia.2017;31:2443).

Background:With new standard-of-care and novel treatment options available in MM, outcomes have improved; however, patients (pts) eventually become refractory to multiple drug classes (Gandhi et al. Leukemia.2019;33:2266). Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate (PDC) that targets aminopeptidases and thereby rapidly releases alkylating agents inside tumor cells. In the United States, melflufen + dex received accelerated approval in RRMM based on results from the phase 2 HORIZON study (Richardson et al. J Clin Oncol. 2021;39:757). In the phase 3, randomized, OCEAN study (NCT03151811), melflufen + dex significantly reduced the risk of disease progression vs pom + dex (progression-free survival [PFS]: hazard ratio [HR], 0.79 [95% CI, 0.64-0.98; P=0.031]) in RRMM (Oncopeptides. Press release. July 8, 2021). This subgroup analysis of OCEAN investigates the impact of prior treatments on efficacy outcomes.

Introduction: Melphalan flufenamide (melflufen) is a peptide-drug conjugate with unique PK properties that rapidly penetrates cells, where it is metabolized to melphalan either directly or through an intermediate metabolite, desethyl-melflufen. Melflufen has only been administered via central venous catheter (CVC); however, peripheral venous catheter (PVC) administration may be preferred by patients if safety and tolerability are acceptable. The ongoing PORT study (NCT04412707) aims to compare the PK of melphalan after central and peripheral administration of melflufen, and to assess the local tolerability of peripheral administration of melflufen. The overall efficacy and safety of melflufen in patients with RRMM will also be evaluated.

The understanding of second‐line use of glucose‐lowering drugs (GLDs) in the general population with type 2 diabetes (T2D) treatment is important as recent results have shown cardiovascular benefits with sodium‐glucose cotransporter‐2 inhibitors (SGLT‐2i) and glucagon‐like peptide‐1 receptor agonists (GLP‐1RA). Our aim was to describe second‐line GLDtreatment patterns in four Nordic countries. All T2D patients treated with GLDbetween 2006 and 2015 were identified in prescribed drug registries in Denmark, Finland, Norway and Sweden, and linked with National Patient and Cause of Death Registries. Second‐line treatment was defined as a prescription of a second GLDclass following ≥6 months of metformin monotherapy. Index was the date of first dispense of the second‐line drug. A rapid uptake of newer GLDs (GLP‐1RA,DPP‐4i and SGLT‐2i) over the 10‐year observation period was seen in Denmark, Finland and Norway, while slower in Sweden. In 2015, 33,880 (3.1%) of 1,078,692 T2D patients initiated second‐line treatment, and newer GLDs were more commonly used in Finland (92%), Norway (71%) and Denmark (70%) vs Sweden (44%). In 2015, the use of older GLDs (insulin and sulphonylureas) was 7‐fold greater in Sweden compared to Finland (49% vs 7%), and 1.6‐fold greater compared with Denmark and Norway (49% vs 30% and 29%, respectively). Despite comparable demography and healthcare systems in four neighbouring countries, surprisingly large differences in second‐line use of newer GLDs were found. With recent evidence of potential cardiovascular benefits with newer GLDs, such differences may have an important impact on cardiovascular outcomes. This multinational study shows large differences in the uptake of newer second‐line glucose‐lowering drugs between four neighbouring and similar countries. In the light of recent paradigm shifting trial results for type 2 diabetes drug treatment, these large differences in modern management of type 2 diabetes are important to understand when planning updated guidelines and future health care.

Radium-223 was minimally myelosuppressive. Multivariate analyses of data from ALSYMPCA patients identified baseline factors that may increase hematologic toxicity risk with radium-223. Extent of disease and degree of prostate-specific antigen elevation were predictive of grade 2-4 anemia; prior docetaxel, and decreased hemoglobin and platelets were predictive of grade 2-4 thrombocytopenia. Patients with these factors should be closely monitored during radium-223 therapy.

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.

Aims To assess the international validity of using hospital record data to compare long-term outcomes in heart attack survivors. Methods and results We used samples of national, ongoing, unselected record sources to assess three outcomes: cause death; a composite of myocardial infarction (MI), stroke, and all-cause death; and hospitalized bleeding. Patients aged 65 years and older entered the study 1 year following the most recent discharge for acute MI in 2002–11 [n = 54 841 (Sweden), 53 909 (USA), 4653 (England), and 961 (France)]. Across each of the four countries, we found consistent associations with 12 baseline prognostic factors and each of the three outcomes. In each country, we observed high 3-year crude cumulative risks of all-cause death (from 19.6% [England] to 30.2% [USA]); the composite of MI, stroke, or death [from 26.0% (France) to 36.2% (USA)]; and hospitalized bleeding [from 3.1% (France) to 5.3% (USA)]. After adjustments for baseline risk factors, risks were similar across all countries [relative risks (RRs) compared with Sweden not statistically significant], but higher in the USA for all-cause death [RR USA vs. Sweden, 1.14 (95% confidence interval 1.04–1.26)] and hospitalized bleeding [RR USA vs. Sweden, 1.54 (1.21–1.96)]. Conclusion The validity of using hospital record data is supported by the consistency of estimates across four countries of a high adjusted risk of death, further MI, and stroke in the chronic phase after MI. The possibility that adjusted risks of mortality and bleeding are higher in the USA warrants further study.