What is established in the medical treatment of heart failure?

New heart failure guidelines offer a changing landscape

Pharmacological Treatments in Heart Failure With Mildly Reduced and Preserved Ejection Fraction: Systematic Review and Network Meta-Analysis

Estimating the Benefits of Combination Medical Therapy in Heart Failure With Mildly Reduced and Preserved Ejection Fraction.

2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.

Sodium-glucose co-transporter 2 inhibitors for heart failure: clinical trial efficacy and clinical practice effectiveness.

Sodium-glucose co-transporter 2 inhibitors in heart failure with preserved ejection fraction: reasons for optimism.

All-Cause Mortality as an End Point for Heart Failure With Preserved Ejection Fraction: Underperformance or Overambitious?

The "Fantastic Four," a term coined in 2021 to refer to the four key drug pillars in the treatment of heart failure with reduced ejection fraction (beta-blockers, renin-angiotensin system and neprilysin inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors, or SGLT2 inhibitors), has demonstrated excellent performance in reducing morbidity and mortality in this setting. However, in heart failure with mildly reduced or preserved ejection fraction, the same benefits were not observed with this combined treatment where, for many years, management in this context was limited to diuretics and comorbidity control. Recently, however, new therapeutic options have emerged, demonstrating effectiveness in reducing cardiovascular outcomes in this specific group: the "Dynamic Duo"-comprising SGLT2 inhibitors and Finerenone-has shown promising results, alongside the introduction of semaglutide as a potential "wild card" treatment for patients with obesity. Despite the ongoing need for therapies that significantly reduce overall mortality, these new treatments have effectively lowered hospitalization rates and improved symptoms in such patients. As a result, a new era in heart failure management is beginning.

Could a Low-Dose Diuretic Polypill Improve Outcomes in Heart Failure With Preserved Ejection Fraction?

<i>Circulation</i> : Clinical Summaries

ResumoO “Quarteto Fantástico”, termo criado em 2021 para se referir aos quatro pilares medicamentosos no tratamento da insuficiência cardíaca com fração de ejeção reduzida (betabloqueadores, inibidores do sistema renina-angiotensina e neprilisina, antagonistas do receptor de mineralocorticoide e inibidores do cotransportador de sódio e glicose II, ou iSGLT2), apresenta excelente desempenho na redução de morbimortalidade nesse cenário. No entanto, no caso da insuficiência cardíaca com fração de ejeção levemente reduzida ou preservada, os mesmos benefícios não foram observados com esse tratamento em conjunto, restando, por muitos anos, apenas o uso de diuréticos e o controle de comorbidades como manejo recomendado nesse contexto. Contudo, recentemente, novas opções terapêuticas demonstraram eficácia na redução dos desfechos cardiovasculares nesse grupo específico da insuficiência cardíaca com fração de ejeção levemente reduzida ou preservada: a “Dupla Dinâmica” composta pelos iSGLT2 e Finerenona, além despontamento da semaglutida como tratamento “coringa” para essa condição associada à obesidade. Embora ainda seja necessária a busca por novas opções terapêuticas que reduzam, de fato, a mortalidade geral nesse contexto, esses novos tratamentos impactaram efetivamente a diminuição da hospitalização e dos sintomas desses pacientes. Por isso, inicia-se uma nova era no manejo da insuficiência cardíaca.

The aim of this study was to assess heart failure (HF) treatment in patients with and without obesity in a large contemporary real-world Western European cohort. Patients with a left ventricular ejection fraction (LVEF) <50% and available information on body mass index (BMI) were selected from the CHECK-HF registry. The CHECK-HF registry included chronic HF patients in the period between 2013 and 2016 in 34 Dutch outpatient clinics. Patients were divided into BMI categories. Differences in HF medical treatment were analysed, and multivariable logistic regression analysis (dichotomized as BMI <30 kg/m2 and ≥30 kg/m2 ) was performed. Seven thousand six hundred seventy-one patients were included, 1284 (16.7%) had a BMI ≥30 kg/m2 , and 618 (8.1%) had a BMI ≥35 kg/m2 . Median BMI was 26.4kg/m2 . Patients with obesity were younger and had a higher rate of comorbidities such as diabetes mellitus, hypertension and obstructive sleep apnoea (OSAS). Prescription rates of guideline-directed medical therapy (GDMT) increased significantly with BMI. The differences were most pronounced for mineralocorticoid receptor antagonists (MRAs) and diuretics. Patients with obesity more often received the guideline-recommended target dose. In multivariable logistic regression, obesity was significantly associated with a higher likelihood of receiving ≥100% of the guideline-recommended target dose of beta-blockers (OR 1.34, 95% CI 1.10-1.62), renin-angiotensin system (RAS)-inhibitors (OR 1.34, 95% CI 1.15-1.57) and MRAs (OR 1.40, 95% CI 1.04-1.87). Guideline-recommended HF drugs are more frequently prescribed and at a higher dose in patients with obesity as compared to HF patients without obesity.

Guideline-Directed Medical Management of Heart Failure with Reduced Ejection Fraction: Improved Outcomes With Quadruple Therapy

In recent years, significant progress has been made in the pharmacologic treatment of heart failure (HF) with reduced ejection fraction (HFrEF), but there is still insufficient evidence for drug therapy for HF with preserved ejection fraction (HFpEF) and mildly reduced ejection fraction (HFmrEF). To compare the outcomes associated with different drug combinations for the treatment of HFpEF and HFmrEF. A search of the PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases was conducted for studies published from inception to October 9, 2021. Randomized clinical trials on the use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs), mineralocorticoid receptor antagonists (MRAs), β-blockers, and sodium-glucose cotransporter 2 (SGLT2) inhibitors for patients with HFpEF or HFmrEF. Data extraction and bias assessment were independently performed by 2 reviewers following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. All data for 3 outcomes were pooled with a fixed-effect model. The main outcomes were first hospitalization for HF, all-cause mortality, and cardiovascular mortality. Hazard ratios (HRs) and 95% credible intervals (CrIs) were evaluated using a bayesian network meta-analysis model. In this analysis, 19 randomized clinical trials, including 20 633 patients with HF and an ejection fraction of 40% or more, without a remarkable risk of bias were included. Compared with placebo, no treatments were associated with a significant reduction in the risk of all-cause death or cardiovascular death. SGLT2 inhibitors, ARNIs, and MRAs were associated with a significant decrease in the risk of HF hospitalization compared with placebo (SGLT2 inhibitors: HR, 0.71 [95% CrI, 0.60-0.83]; ARNIs: HR, 0.76 [95% CrI, 0.61-0.95]; MRAs: HR, 0.83 [95% CrI, 0.69-0.99]), and SGLT2 inhibitors were the optimal drug class in terms of reducing the risk for HF admission. Sensitivity analysis results demonstrated a progressive decrease in the risk of HF admission and an advance in mean rank associated with the increasing use of drug classes. The findings of this study suggest that SGLT2 inhibitors were the optimal drug class for HFpEF and HFmrEF, consistent with the most recent guideline recommendation. The incremental use of combinations of SGLT2 inhibitors, ACE inhibitors or ARBs, and β-blockers may be associated with accumulative benefits in HF hospitalization rather than all-cause death among patients with HFpEF and HFmrEF.

Heart failure (HF) remains a major clinical challenge, with two main phenotypes: heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). These conditions exhibit distinct pathophysiology, clinical manifestations, and therapeutic responses, requiring distinct management approaches. The four pillars of HFrEF therapy—renin-angiotensin system (RAS) inhibitors, β-blockers, mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 (SGLT2) inhibitors—have been shown to reduce mortality and morbidity. In contrast, HFpEF management focuses more on risk factor control and symptom-based therapy, with SGLT2 inhibitors being the only treatment that has shown significant clinical benefit. This literature review aims to evaluate the different roles of the four pillars of therapy in both phenotypes of heart failure and their implications for clinical practice. Although HFrEF treatment has made significant progress with strong clinical trial evidence, HFpEF management still requires further exploration to identify more effective strategies. Therefore, a deeper understanding of each phenotype's pathophysiology and therapeutic response is essential to improve patient outcomes and optimize heart failure management.