Report from the 5th cardiovascular outcome trial (CVOT) summit.

The 5th Cardiovascular Outcome Trial (CVOT) Summit was held in Munich on October 24th-25th, 2019. As in previous years, this summit served as a reference meeting for in-depth discussions on the topic of recently completed and presented CVOTs. This year, focus was placed on the CVOTs CAROLINA, CREDENCE, DAPA-HF, REWIND, and PIONEER-6. Trial implications for diabetes management and the impact on new treatment algorithms were highlighted for diabetologists, cardiologists, endocrinologists, nephrologists, and general practitioners. Discussions evolved from CVOTs to additional therapy options for heart failure (ARNI), knowledge gained for the treatment and prevention of heart failure and diabetic kidney disease in populations with and without diabetes, particularly using SGLT-2 inhibitors and GLP-1 receptor agonists. Furthermore, the ever increasing impact of CVOTs and substances tested for primary prevention and primary care was discussed. The 6th Cardiovascular Outcome Trial Summit will be held in Munich on October 29th-30th, 2020 (https://www.cvot.org).

Costs and healthcare utilisation of patients with heart failure in Spain.

BACKGROUND: Increasing the knowledge about heart failure (HF) costs and their determinants is important to ascertain how HF management can be optimized, leading to a significant decrease of HF costs. This study evaluated the cumulative costs and healthcare utilisation in HF patients in Spain. METHODS: Observational, retrospective, population-based study using BIG-PAC database, which included data from specialized and primary care of people ≥18 years, from seven autonomous communities in Spain, who received care for HF between 2015 and 2019. The 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 17,163 patients with HF (year 2015: mean age 77.3 ± 11.8 years, 53.5% men, 51.7% systolic HF, 43.6% on NYHA functional class II). During the 2015-2019 period, total HF associated costs reached 15,373 Euros per person, being cardiovascular disease hospitalizations the most important determinant (75.8%), particularly HF hospitalizations (51.0%). Total medication cost accounted for 7.0% of the total cost. During this period, there was a progressive decrease of cardiovascular disease hospital costs per year (from 2834 Euros in 2015 to 2146 Euros in 2019, P < 0.001), as well as cardiovascular and diabetic medication costs. CONCLUSIONS: During the 2015-2019 period, costs of HF patients in Spain were substantial, being HF hospitalizations the most important determinant. Medication costs represented only a small proportion of total costs. Improving HF management, particularly through the use of drugs that reduce HF hospitalization may be helpful to reduce HF burden.

DAPA-HF applicability: the point of view of a cardiology setting.

Randomised clinical trials, observational studies, and meta-analyses have shown that sodium-glucose cotransporter 2 inhibitors (SGLT2-i) reduce the risk of hospitalisation for heart failure (HF), chronic kidney disease (CKD) progression, and mortality in patients with HF, irrespective of the presence of type 2 diabetes mellitus. However, real-world epidemiology may differ from clinical trial populations, thereby limiting generalisability and delaying the introduction of novel treatments in clinical practice.The aim of the present study was to assess the prevalence of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) inclusion criteria in a population of HF with reduced ejection fraction (HFrEF) patients enrolled in the Italian Network on Heart Failure (IN-HF) registry.Overall, 3415 IN-HF patients matched the 4744 patients in DAPA-HF, overlapping for most baseline characteristics (e.g. similar average ejection fraction), with a slightly lower prevalence of type 2 diabetes and of HF ischaemic aetiology and a higher percentage of NYHA class II patients. The theoretical eligibility to DAPA-HF in a cardiology setting resulted to be 73%.The availability of an easily accessible database from a large nationwide prospective registry allows to provide insights to clinicians and policy makers on the applicability of the DAPA HF findings to a contemporary population of HFrEF patients followed by cardiologists. It is reasonable to assume that the results of this analysis can be applicable to the entire SGLT2-ir class of drugs.

Clinical characteristics, management, and one-year risk of complications among patients with heart failure with and without type 2 diabetes in Spain.

OBJECTIVE: This work aims to describe the clinical characteristics and therapeutic management and to determine cardiovascular outcomes after one year of follow-up in a contemporaneous population with heart failure (HF) with and without type 2 diabetes in Spain. These factors were also analyzed in the DAPA-HF-like population (patients who met most inclusion criteria of the DAPA-HF trial) and in patients treated with SGLT2 inhibitors at baseline. METHODS: This work is an observational, retrospective, population-based study using the BIG-PAC database. The index date was January 1, 2019. People aged ≥ 18 years who received care for HF in 2019 were selected. Events that occurred in 2019 were analyzed. RESULTS: We identified 21,851 patients with HF (age 78.0 ± 11.3 years, 53.0% men, 50.9% with HF with reduced left ventricular ejection fraction, 44.5% in NYHA functional class II). HF prevalence was 1.88% and incidence was 2.83 per 1,000 person-years. Regarding HF treatments, 66.1% were taking renin-angiotensin system inhibitors, 69.4% beta blockers, 31.2% aldosterone antagonists, and 7.5% sacubitril/valsartan. During the year of follow-up, 29.8% had HF decompensation which led to hospitalization (mean time to first event of 120.9 ± 72.5 days), 12.3% died, and 8.1% died during hospitalization. Events were more common among patients with type 2 diabetes. Hospitalizations for HF were more common in the DAPA-HF-like population. CONCLUSIONS: In Spain, the population with HF is elderly and has many comorbidities. Approximately half of patients have HF with reduced left ventricular ejection fraction. There is room for improvement in HF management, particularly through the use of drugs that reduce both HF hospitalization and mortality, in order to reduce the burden of HF.

The Role of Dapagliflozin in the Management of Heart Failure: An Update on the Emerging Evidence.

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.

Sodium-glucose co-transporter-2 inhibitors eligibility in patients with heart failure with reduced ejection fraction.

BACKGROUND: The sodium-glucose co-transporter-2 (SGLT2) inhibitors dapagliflozin and empagliflozin have been demonstrated to reduce adverse cardiovascular outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Limited data are available characterizing the generalizability of SGLT2 inhibitors treatment in the clinical practice. The aim of the study was to evaluate the proportion of outpatients with HFrEF that would be eligible for SGLT2 inhibitors in a contemporary real-world population. METHODS: We retrospectively evaluated patients with chronic stable HFrEF followed-up at the HF outpatient clinic of our institution. Patients' eligibility was assessed according to the entry criteria of DAPA-HF (dapagliflozin) and EMPEROR-Reduced (empagliflozin) trials and to US Food and Drug Administration (FDA) label criteria (only dapagliflozin). RESULTS: A total of 441 HFrEF patients was enrolled. According to the major inclusion and exclusion criteria from DAPA-HF and EMPEROR-Reduced trials, 198 (45%) patients would be candidates for initiation of both dapagliflozin and empagliflozin, 61 (14%) would be eligible only to dapagliflozin and 23 (5%) only to empagliflozin, without significant differences between diabetic and non-diabetic patients (p = 0.23). Among patients not suitable for gliflozins treatment (159 patients; 36%), the major determinant of ineligibility was the failure to achieve the predefined NT-proBNP inclusion threshold. Excluding NTproBNP as per FDA label criteria, dapagliflozin eligibility increased to 86%. CONCLUSIONS: In our real-world analysis a large proportion of HFrEF patients would be candidates for initiation of SGLT2 inhibitors, supporting its broad generalizability in clinical practice. This would be expected to reduce morbidity and mortality in eligible patients.

[Dapagliflozin in the prevention and treatment of heart failure]. / Dapagliflozina en la prevención y tratamiento de la insuficiencia cardiaca.

To substantially reduce the risk of hospitalization and death among subjects with heart failure (HF) and reduced left ventricular ejection fraction, it is necessary to make a comprehensive approach of the different neurohormonal systems that are implied in its etiopathogenesis, including not only sympathetic nervous system, and renin-angiotensin system, but also vasoactive peptides and sodium-glucose transport protein 2. The DAPA-HF trial demonstrated that the addition of dapagliflozin to the standard treatment in HF with reduced left ventricular ejection fraction, markedly decreases the risk of cardiovascular death, HF hospitalization and overall death. In addition, dapagliflozin improves functional class and quality of life. Importantly, the prognostic benefit starts early after initiating treatment with dapagliflozin, regardless baseline therapy or the presence of diabetes. All these evidences make dapagliflozin as one of the mainstays of treatment for the management of HF with reduced left ventricular ejection fraction.

[Practical approach of dapagliflozin for the treatment of heart failure. Role of primary care physician]. / Abordaje práctico de dapagliflozina en el tratamiento de la insuficiencia cardíaca. Papel del médico de atención primaria.

Despite traditional treatments, morbidity and mortality of patients with heart failure (HF) and reduced left ventricular ejection fraction remains unacceptably high. Traditionally, guidelines recommended a step by step approach in the management of this population. However, this approach could delay the prescription of some drugs with proven efficacy on morbidity and prognosis. As current HF guidelines recommend, an initial comprehensive approach with the aim of targeting all neurohormonal systems that are implied in the etiopathogenesis of HF seems necessary. The DAPA-HF trial demonstrated that dapagliflozin markedly reduces the risk of HF hospitalization, and also improves prognosis. Consequently, dapagliflozin should be considered as a first-line therapy in the management of these patients. On the other hand, primary care physicians are essential for the prevention and treatment of patients with HF and reduced left ventricular ejection fraction. As a result, it is mandatory that they know when and how dapagliflozin should be used. In this review, a practical approach for an appropriate use of this drug is provided.

DAPA-HF trial: dapagliflozin evolves from a glucose-lowering agent to a therapy for heart failure.

Heart failure (HF) continues to be a major global health problem with a notable impact in terms of morbidity and mortality and so, in consequence, with a large unmet necessity for new therapies. The inhibition of sodium-glucose cotransporter 2 (SGLT2) causes glycosuria and natriuresis, leading to reductions in hyperglycemia (antidiabetic effect), body weight, and blood pressure. In this context, outcome trials have been shown to reduce hospitalizations for HF in patients with type 2 diabetes mellitus treated with SGLT2 inhibitors. The underlying protective cardiovascular (CV) mechanisms of these agents are complex, multifactorial, and not entirely understood as, in addition to a diuretic-like function, SGLT2 inhibitors may mitigate glycemic-related toxicity, promote ketogenesis, increase hematocrit, and exert antihypertrophic, antifibrotic, and antiremodeling properties. The DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial enrolled 4744 patients with HF and reduced ejection fraction (EF) who were receiving excellent guideline-directed treatment before the addition of dapagliflozin (a SGLT2 inhibitor) or placebo. The DAPA-HF trial clearly showed that dapagliflozin was superior to placebo at preventing CV deaths and HF events. The relative and absolute risk reductions in death and hospitalizations were consistent across subgroups including patients with and without diabetes; so, in consequence, dapagliflozin represents the first in a new class of drug for HF with reduced EF. The recently published Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients With Heart Failure With Reduced Ejection Fraction (DEFINE-HF) trial is also described in this review as well as the thought-to-be mechanisms of action of SGLT2 inhibitors beyond their known glucose-lowering effects. There is a vast, ambitious, and promising ongoing clinical investigation program with dapagliflozin and other SGLT2 inhibitors, which may result in changes to the therapeutic approach to HF in a relatively short time.

Características clínicas, manejo y riesgo de complicaciones a un año en pacientes con insuficiencia cardíaca con y sin diabetes tipo 2 en España / Clinical characteristics, management, and one-year risk of complications among patients with heart failure with and without type 2 diabetes in Spain

Objetivos: Describir las características clínicas y el manejo terapéutico y determinar los eventos cardiovasculares tras un año de seguimiento en una población contemporánea con insuficiencia cardíaca (IC) con y sin diabetes tipo 2 en España. También se analizó en la población DAPA-HF (pacientes que cumplieron la mayoría de los criterios de inclusión del estudio DAPA-HF) y en los pacientes tratados basalmente con inhibidores SGLT2.Métodos: Estudio observacional, retrospectivo, poblacional, empleando la base de datos BIG-PAC. La fecha índice fue 1 de enero de 2019. Se seleccionaron sujetos≥18 años que recibieron tratamiento por IC en 2019. Se analizaron los eventos durante 2019.Resultados: Se identificaron 21.851 pacientes con IC (78±11,3 años; 53% varones; 50,9% IC con fracción de eyección reducida; 44,5% en clase funcional NYHA II). La prevalencia de IC fue del 1,88% y la incidencia 2,83 por 1.000 pacientes-año. El 66,1% tomaba inhibidores del sistema renina-angiotensina, el 69,4% betabloqueantes, el 31,2% antialdosterónicos y el 7,5% sacubitrilo/valsartán. Durante el año de seguimiento, el 29,8% fue hospitalizado por descompensación de la IC (tiempo medio primer evento 120,9±72,5 días), un 12,3% murieron, un 8,1% murieron durante la hospitalización. Los eventos fueron más frecuentes en los pacientes con diabetes tipo 2. Las hospitalizaciones por IC fueron más comunes en la población similar a DAPA-HF.Conclusiones: En España, la población con IC es anciana y tiene muchas comorbilidades. Aproximadamente la mitad de los pacientes tienen IC con fracción de eyección reducida. Existe margen de mejora en el manejo de la IC, en particular mediante el empleo de aquellos fármacos que reducen tanto la hospitalización por IC como la mortalidad, para disminuir la carga de IC (AU)

Objective: This work aims to describe the clinical characteristics and therapeutic management and to determine cardiovascular outcomes after one year of follow-up in a contemporaneous population with heart failure (HF) with and without type 2 diabetes in Spain. These factors were also analyzed in the DAPA-HF-like population (patients who met most inclusion criteria of the DAPA-HF trial) and in patients treated with SGLT2 inhibitors at baseline.Methods: This work is an observational, retrospective, population-based study using the BIG-PAC database. The index date was January 1, 2019. People aged≥18 years who received care for HF in 2019 were selected. Events that occurred in 2019 were analyzed.Results: We identified 21,851 patients with HF (age 78.0±11.3 years, 53.0% men, 50.9% with HF with reduced left ventricular ejection fraction, 44.5% in NYHA functional class II). HF prevalence was 1.88% and incidence was 2.83 per 1,000 person-years. Regarding HF treatments, 66.1% were taking renin-angiotensin system inhibitors, 69.4% beta blockers, 31.2% aldosterone antagonists, and 7.5% sacubitril/valsartan. During the year of follow-up, 29.8% had HF decompensation which led to hospitalization (mean time to first event of 120.9±72.5 days), 12.3% died, and 8.1% died during hospitalization. Events were more common among patients with type 2 diabetes. Hospitalizations for HF were more common in the DAPA-HF-like population.Conclusions: In Spain, the population with HF is elderly and has many comorbidities. Approximately half of patients have HF with reduced left ventricular ejection fraction. There is room for improvement in HF management, particularly through the use of drugs that reduce both HF hospitalization and mortality, in order to reduce the burden of HF (AU)

Lo mejor del Congreso AHA/ACC 2019 / The best of the 2019 AHA/ACC Congress / O melhor do Congresso da AHA/ACC 2019

Resumen: Del 16 al 18 de noviembre de 2019 se celebró en la ciudad de Philadelphia una nueva reunión del congreso anual del American College of Cardiology. Es uno de los eventos más relevantes de la cardiología mundial, y contó en esta oportunidad con la participación de destacados profesionales que presentaron los últimos ensayos clínicos en las sesiones de Late Breaking Science, abordando diferentes aspectos de la especialidad: estrategias innovadoras para reducir el riesgo cardiovascular, resultados de los ensayos de isquemia, controversias en el manejo contemporáneo de la estenosis aórtica, estado del arte del manejo de pacientes con síndromes coronarios agudos, desafíos en insuficiencia cardíaca y nuevas fronteras en la terapia lipídica. A continuación presentamos un resumen de los principales trabajos presentados: - The Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure Trial (DAPA-HF). - The COLchicine Cardiovascular Outcomes Trial (COLCOT). - Global Comparison of a Rivaroxaban-Based Antithrombotic Strategy versus an Antiplatelet-Based Strategy After Transcathether Aortic Replacement to Optimize Clinical Outcomes (GALILEO) Trial: Primary Results. - RECOVERY: Early Surgery versus Conventional Management for Asymptomatic Severe Aortic Stenosis. - International Study of Comparative Health Effectiveness With Medical and Invasive Approaches: Primary Report of Clinical Outcomes (ISCHEMIA).

Summary: A new meeting of the annual congress of the American College of Cardiology, was held from November 16 to 18 last year; located in the city of Philadelphia. As one of the most important events in global cardiology, it was attended by leading professionals who were the last clinical trials in the Late Breaking Science sessions, which addressed different aspects of the specialty: innovative strategies to reduce cardiovascular risk, results of the trials of ischemia, controversies in the contemporary management of aortic stenosis, state of the art of the management of patients with acute coronary syndromes, challenges in heart failure and new frontiers in lipid therapy. We will make a brief summary of the main presented trials: - The Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure Trial (DAPA-HF). - The COLchicine Cardiovascular Outcomes Trial (COLCOT). - Global Comparison of a Rivaroxaban-Based Antithrombotic Strategy versus an Antiplatelet-Based Strategy After Transcathether Aortic Replacement to Optimize Clinical Outcomes (GALILEO) Trial: Primary Results. - RECOVERY: Early Surgery versus Conventional Management for Asymptomatic Severe Aortic Stenosis. - International Study of Comparative Health Effectiveness With Medical and Invasive Approaches: Primary Report of Clinical Outcomes (ISCHEMIA).

Resumo: Uma nova reunião do congresso anual do Colégio Americano de Cardiologia, foi realizada de 16 a 18 de novembro do ano passado; localizado na cidade de Filadélfia. Como um dos eventos mais importantes da cardiologia global, contou com a presença de profissionais líderes que apresentaram os últimos ensaios clínicos nas sessões de Late Breaking Science, que abordaram diferentes aspectos da especialidade: estratégias inovadoras para reduzir o risco cardiovascular, resultados dos ensaios de isquemia, controvérsias no tratamento contemporâneo da estenose aórtica, estado da arte do tratamento de pacientes com síndromes coronárias agudas, desafios na insuficiência cardíaca e novas fronteiras na terapia lipídica. Faremos um breve resumo dos principais trabalhos apresentados: - The Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure Trial (DAPA-HF). - The COLchicine Cardiovascular Outcomes Trial (COLCOT). - Global Comparison of a Rivaroxaban-Based Antithrombotic Strategy versus an Antiplatelet-Based Strategy After Transcathether Aortic Replacement to Optimize Clinical Outcomes (GALILEO) Trial: Primary Results. - RECOVERY: Early Surgery versus Conventional Management for Asymptomatic Severe Aortic Stenosis. - International Study of Comparative Health Effectiveness With Medical and Invasive Approaches: Primary Report of Clinical Outcomes (ISCHEMIA).