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Background Despite renin–angiotensin–aldosterone system blockade and immunosuppressive treatment, focal segmental glomerulosclerosis (FSGS) often progresses to kidney failure. The objective of this prespecified analysis of the dapagliflozin and prevention of adverse outcomes in chronic kidney disease trial (DAPA-CKD) was to assess efficacy and safety of dapagliflozin in a small subgroup of participants with FSGS confirmed by kidney biopsy. Methods In DAPA-CKD, patients with an estimated glomerular filtration rate (eGFR) 25–75 mL/min/1.73 m2 and urinary albumin:creatinine ratio (UACR) 200–5000 mg/g (22.6–565 mg/mol) were randomized to dapagliflozin 10 mg once daily or placebo as an adjunct to standard care and followed for median 2.4 years. The primary composite endpoint was sustained eGFR decline ≥50%, end-stage kidney disease, or kidney or cardiovascular death. The endpoint of interest for this analysis was eGFR slope (acute effects from baseline to Week 2 and chronic effects from Week 2 to end of treatment). Results Of 104 participants with biopsy-confirmed FSGS, 45 were randomized to dapagliflozin and 59 to placebo. Mean (standard deviation) age was 54.0 (14.3) years, mean eGFR 41.9 (11.5) mL/min/1.73 m2 and median (interquartile range) UACR 1248 (749–2211) mg/g. The primary outcome occurred in 4 (8.9%) and 7 (11.9%) participants randomized to dapagliflozin and placebo, respectively [hazard ratio 0.62, 95% confidence interval (95% CI) 0.17, 2.17]. Dapagliflozin led to a larger acute reduction (standard error) in eGFR compared with placebo (−4.5, 95% CI −5.9 to −3.1 versus −0.9, −2.1 to 0.4 mL/min/1.73 m2/2 weeks). Thereafter, mean rates of chronic eGFR decline with dapagliflozin and placebo were −1.9 (−3.0, −0.9) and −4.0 (−4.9, −3.0) mL/min/1.73 m2/year, respectively (difference 2.0, 95% CI 0.6 to 3.5, mL/min/1.73 m2/year). Adverse events leading to study drug discontinuation were similar in both groups; there were fewer serious adverse events with dapagliflozin. Conclusions Among DAPA-CKD participants with FSGS, dapagliflozin reduced the rate of chronic decline of eGFR compared with placebo, although this difference was not statistically significant.

Immunoglobulin A (IgA) nephropathy is a common form of glomerulonephritis, which despite use of renin-angiotensin-aldosterone-system blockers and immunosuppressants, often progresses to kidney failure. In the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease trial, dapagliflozin reduced the risk of kidney failure and prolonged survival in participants with chronic kidney disease with and without type 2 diabetes, including those with IgA nephropathy. Participants with estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m2 and urinary albumin-to-creatinine ratio 200-5000 mg/g (22.6-565 mg/mol) were randomized to dapagliflozin 10mg or placebo, as adjunct to standard care. The primary composite endpoint was a sustained decline in eGFR of 50% or more, end-stage kidney disease, or death from a kidney disease-related or cardiovascular cause. Of 270 participants with IgA nephropathy (254 [94%] confirmed by previous biopsy), 137 were randomized to dapagliflozin and 133 to placebo, and followed for median 2.1 years. Overall, mean age was 51.2 years; mean eGFR, 43.8 mL/min/1.73m2; and median urinary albumin-to-creatinine ratio, 900 mg/g. The primary outcome occurred in six (4%) participants on dapagliflozin and 20 (15%) on placebo (hazard ratio, 0.29; 95% confidence interval, 0.12, 0.73). Mean rates of eGFR decline with dapagliflozin and placebo were −3.5 and −4.7 mL/min/1.73m2/year, respectively. Dapagliflozin reduced the urinary albumin-to-creatinine ratio by 26% relative to placebo. Adverse events leading to study drug discontinuation were similar with dapagliflozin and placebo. There were fewer serious adverse events with dapagliflozin, and no new safety findings in this population. Thus, in participants with IgA nephropathy, dapagliflozin reduced the risk of chronic kidney disease progression with a favorable safety profile.

Objectives: To describe the epidemiology, clinical profile, treatments, and to determine cardiovascular and renal outcomes after two years of follow-up in a contemporary chronic kidneay disease (CKD) population in Spain. This was also analyzed among the DAPA-CKD-like population (patients who met most inclusion criteria of DAPA-CKD trial). Methods: Observational, retrospective, population-based study using BIG-PAC database. The CKD population was defined as patients ≥18 years, with at least one diagnostic code of CKD prior to the index date (January 1st, 2018). CKD was defined as estimated glomerular filtration rate (eGFR) 30 mg/g. Results: We identified 56,435 CKD patients after exclusions (76.4 years, 52.2% men, urine albumin-to-creatinine ratio 390.8 mg/g, eGFR 49.7 mL/min/1.73 m2). CKD prevalence was 4.91% and incidence 2.10 per 1000 patient-years. Regarding treatments, 69.2% were taking renin-angiotensin system inhibitors (only 4.2% at maximal doses) and 3.5% of diabetic patients SGLT-2 inhibitors. During the two years of follow-up, rates of heart failure, all-cause death, myocardial infarction, stroke, and CKD were 17.9, 12.1, 7.2, 6.3, and 5.9 events per 100 patient-years, respectively. During this period, 44% of patients were hospitalized, and 6.8% died during hospitalization. Cardiovascular outcomes were more common in the DAPA-CKD-like population. Conclusions: In Spain, CKD population is older and comorbidities, including diabetes and heart failure, are common. Cardiovascular and renal outcomes are frequent. There is room for improvement in CKD management, particularly through the use of drugs with proven cardiovascular and renal benefit. Resumen: Objetivos: Describir la epidemiología, el perfil clínico, los tratamientos y los eventos cardiovasculares y renales, tras 2 años de seguimiento en una población contemporánea con enfermedad renal crónica (ERC) en España. También se analizó en la población tipo DAPA-CKD (pacientes que cumplían la mayoría de criterios del estudio DAPA-CKD). Métodos: Estudio observacional, retrospectivo, poblacional, empleando la base de datos BIG-PAC. La población con ERC se definió como pacientes ≥ 18 años, con al menos un código diagnóstico de ERC antes de la fecha índice (01/01/2018). La ERC se definió como filtrado glomerular estimado (FGe) 30 mg/g. Resultados: Se identificaron 56.435 pacientes con ERC, tras exclusiones (76,4 años, 52,2% varones, cociente albúmina-creatinina 390,8 mg/g, FGe 49,7 ml/min/1,73 m2). La prevalencia fue del 4,91% y la incidencia 2,10/1.000 pacientes/año. El 69,2% tomaba inhibidores del sistema renina-angiotensina (solo el 4,2% a dosis máximas) y el 3,5% de los diabéticos inhibidores SGLT-2. Tras 2 años, las tasas de insuficiencia cardiaca, muerte, infarto de miocardio, ictus y ERC fueron 17,9; 12,1; 7,2; 6,3; 5,9 eventos/100 pacientes/año, respectivamente. Además, el 44% hospitalizaron y el 6,8% murieron durante la hospitalización. Los eventos cardiovasculares fueron más frecuentes en la población tipo DAPA-CKD. Conclusiones: En España, la población con ERC es mayor, y las comorbilidades, incluyendo diabetes e insuficiencia cardiaca, comunes. Los eventos cardiovasculares y renales son frecuentes. Hay margen de mejora en el manejo de la ERC, especialmente a través del empleo de fármacos con beneficio cardiovascular y renal.

The 6th Cardiovascular Outcome Trial (CVOT) Summit “Cardiovascular and Renal Outcomes 2020” was the first to be held virtually on October 29–30, 2020. As in previous years, this summit served as reference meeting for in-depth discussions on the topic of recently completed and presented major outcome trials. This year, focus was placed on the outcomes of VERTIS-CV, EMPEROR-Reduced, DAPA-CKD, and FIDELIO-DKD. Trial implications for diabetes management and the impact on new treatment algorithms were highlighted for diabetologists, cardiologists, endocrinologists, nephrologists, and general practitioners. Discussion evolved from major outcome trials using SGLT-2 inhibitors for treatment and prevention of heart failure and chronic kidney disease in people with and without diabetes, to additional therapy options for chronic kidney disease with a novel mineralocorticoid receptor antagonist. Furthermore, challenges in diabetes management like COVID-19 and obesity, as well as novel treatment strategies and guidelines, were discussed.The 7th Cardiovascular Outcome Trial Summit will be held virtually on November, 18–19, 2021 (http://www.cvot.org).

The burden and cost of heart failure management, primarily in the form of hospitalization in the setting of decompensated heart failure, continue to be some of the biggest clinical challenges in cardiovascular medicine. In recently published randomized controlled trials, including DAPA-HF, sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin was shown to reduce hospitalization from heart failure or mortality associated with cardiovascular causes, when added to existing guideline-directed medical therapy. The American College of Cardiology (ACC) released a Clinical Pathway guideline that recommends the use of dapagliflozin in clinical management of heart failure, with or without diabetes. Furthermore, the results of the DAPA-CKD trial broaden the utility of dapagliflozin as a therapeutic option in patients with advanced kidney disease. In this article, the authors explore the existing evidence on dapagliflozin in heart failure with reduced ejection fraction and highlight the need for further research on uses of dapagliflozin in the world of heart failure.

Background Data about the impact of chronic kidney disease (CKD) on health care costs in Spain are scarce This study was aimed to evaluate cumulative costs and healthcare utilisation in CKD in Spain. Methods Observational, retrospective, population-based study, which included adults who received care for CKD between 2015 and 2019. Healthcare and medication costs were summarized on a yearly basis starting from the index date (1st January 2015), and then cumulatively until 2019. Results We identified 44,214 patients with CKD (year 2015: age 76.4 ± 14.3 years, 49.0% women, albumin-to-creatinine ratio 362.9 ± 176.8 mg/g, estimated glomerular filtration rate 48.7 ± 13.2 mL/min/1.73 m2). During the 2015–2019 period, cumulative CKD associated costs reached 14,728.4 Euros, being cardiovascular disease hospitalizations, particularly due to heart failure and CKD, responsible for 77.1% of costs. Total medication cost accounted for 6.6% of the total cost. There was a progressive decrease in cardiovascular disease hospital costs per year (from 2741.1 Euros in 2015 to 1.971.7 Euros in 2019). This also occurred with cardiovascular and diabetic medication costs, as well as with the proportion of hospitalizations and mortality. Costs and healthcare resources use were higher in the DAPA-CKD like population, but also decreased over time. Conclusions Between 2015 and 2019, costs of patients with CKD in Spain were high, with cardiovascular hospitalizations as the key determinant. Medication costs were responsible for only a small proportion of total CKD costs. Improving CKD management, particularly with the use of cardiovascular and renal protective medications may be helpful to reduce CKD burden.

Background Sodium glucose transporter 2 inhibitors (SGLT2-i) reduce renal and cardiovascular events in patients with type 2 diabetes (T2D) and their use is recommended by the 2020 KDIGO guidelines in patients with T2D and chronic kidney disease (CKD). The aim of this study is to estimate the proportion of patients with T2D and CKD in the US that should be treated with these agents for renal and cardiovascular protection. Methods We conducted a retrospective analysis of 2005–2018 National Health and Nutrition Examination Survey (NHANES) data. We focused on participants with a prior diagnosis of diabetes or that met diagnostic criteria for diabetes during the survey, with the exclusion of probable type 1 diabetic patients. Inclusion criteria for completed and ongoing renal and cardiovascular outcome trials in patients with CKD were applied. Results We estimated that 35.3% of patients with T2D in the US (projected to 8.96 million) should be treated with SGLT2-i according to the 2020 KDIGO guidelines. Moreover, 2.9–10.1% (projected to 0.75–2.55 million) met the inclusion criteria for dedicated kidney outcome trials, which were focused on a population of individuals with proteinuria. Conclusions About a third of patients with T2D in the US should be treated with an SGLT2-i. While compelling evidence of renal protection is present for patients with proteinuria, all patients with CKD obtain a cardiovascular benefit with this class of drugs.

Resumen: La necesidad de distanciamiento social impuesta por la actual pandemia por coronavirus obligó a las diferentes sociedades científicas a realizar sus actividades en formato completamente virtual. La Sociedad Europea de Cardiología no ha sido la excepción. Desde el 29 de agosto al 1 de septiembre de 2020 se celebró este evento sin precedentes que, además de contar con 125.000 profesionales de 213 países, permitió el acceso gratuito a todos los cibernautas. De esta manera, la actualidad en cardiología pudo llegar a todos los rincones del mundo, pese a las circunstancias tan complejas. Como ya es tradición de la revista, realizamos un resumen de los principales ensayos presentados durante el congreso: - Early Rhythm-Control Therapy in Patients with Atrial Fibrillation (EAST-AFNET 4) - Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure (The EMPEROR-Reduced Trial Investigators) - Efficacy and Safety of Mavacamten in Adults with Symptomatic Obstructive Hypertrophic Cardiomyopathy (EXPLORER-HCM) - Angiotensin Receptor Neprilysin Inhibition Compared with Individualized Medical Therapy for Comorbidities in Patients with Heart Failure and Preserved Ejection Fraction (The PARALLAX Trial) - A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients with Chronic Kidney Disease (DAPA-CKD) - Aspirin with or without Clopidogrel after Transcatheter Aortic-Valve Implantation (POPULAR TAVI (Cohort A)) - Colchicine in Patients with Chronic Coronary Disease (The LoDoCo2 Trial Investigators) - Pharmacological Blood Pressure-Lowering for Primary and Secondary Prevention of Cardiovascular Disease Across Different Levels of Blood Pressure (BPLTTC) - Continuing versus suspending angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: Impact on adverse outcomes in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (The BRACE CORONA Trial) - Randomized Trial of Transfusion Strategies in Patients with Myocardial Infarction and Anemia (REALITY Trial) Summary The need for social distancing imposed by the current coronavirus pandemic, forced the different scientific societies to carry out their activities in a completely virtual format. And the European Society of Cardiology has not been the exception. From August 29 to September 1 of 2020, this unprecedented event was held which, in addition to having 125,000 health professionals from 213 countries, allowed free access to all netizens. In this way, current affairs in cardiology could reach all corners of the world, despite such complex circumstances. As is the tradition of the magazine, we present a summary of the main essays presented during the congress: - Early Rhythm-Control Therapy in Patients with Atrial Fibrillation (EAST-AFNET 4) - Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure (The EMPEROR-Reduced Trial Investigators) - Efficacy and Safety of Mavacamten in Adults with Symptomatic Obstructive Hypertrophic Cardiomyopathy (EXPLORER-HCM) - Angiotensin Receptor Neprilysin Inhibition Compared with Individualized Medical Therapy for Comorbidities in Patients with Heart Failure and Preserved Ejection Fraction (The PARALLAX Trial) - A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients with Chronic Kidney Disease (DAPA-CKD) - Aspirin with or without Clopidogrel after Transcatheter Aortic-Valve Implantation (POPULAR TAVI (Cohort A)) - Colchicine in Patients with Chronic Coronary Disease (The LoDoCo2 Trial Investigators) - Pharmacological Blood Pressure-Lowering for Primary and Secondary Prevention of Cardiovascular Disease Across Different Levels of Blood Pressure (BPLTTC) - Continuing versus suspending angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: Impact on adverse outcomes in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (The BRACE CORONA Trial) - Randomized Trial of Transfusion Strategies in Patients with Myocardial Infarction and Anemia (REALITY Trial) Resumo A necessidade de distanciamento social imposto pela atual pandemia do coronavírus, obrigou as diferentes sociedades científicas a desenvolverem suas atividades de forma totalmente virtual. E a Sociedade Europeia de Cardiologia não foi exceção. De 29 de agosto a 1º de setembro 2020, foi realizado esse evento inédito que, além de contar com 125.000 profissionais de saúde de 213 países, possibilitou o acesso gratuito a todos os internautas. Dessa forma, a atualidade da cardiologia pode atingir todos os cantos do mundo, apesar de circunstâncias tão complexas. Como é tradição da revista, apresentamos um resumo dos principais ensaios apresentados durante o congresso: - Early Rhythm-Control Therapy in Patients with Atrial Fibrillation (EAST-AFNET 4) - Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure (The EMPEROR-Reduced Trial Investigators) - Efficacy and Safety of Mavacamten in Adults with Symptomatic Obstructive Hypertrophic Cardiomyopathy (EXPLORER-HCM) - Angiotensin Receptor Neprilysin Inhibition Compared with Individualized Medical Therapy for Comorbidities in Patients with Heart Failure and Preserved Ejection Fraction (The PARALLAX Trial) - A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients with Chronic Kidney Disease (DAPA-CKD) - Aspirin with or without Clopidogrel after Transcatheter Aortic-Valve Implantation (POPULAR TAVI (Cohort A)) - Colchicine in Patients with Chronic Coronary Disease (The LoDoCo2 Trial Investigators) - Pharmacological Blood Pressure-Lowering for Primary and Secondary Prevention of Cardiovascular Disease Across Different Levels of Blood Pressure (BPLTTC) - Continuing versus suspending angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: Impact on adverse outcomes in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (The BRACE CORONA Trial) - Randomized Trial of Transfusion Strategies in Patients with Myocardial Infarction and Anemia (REALITY Trial)