Digoxin – ABC CARDIOL

ABCHF

Viewpoint

The Use of Digitalis: A Reflection of Medicine as the Science of Provisional Truths

Plinio J. Wolf et al. Carolina Casadei dos Santos João Rossi Marco Aurelio A. Finger … Victor B. M. Mattos Raphael Rossi Edileide Barros Correia Marco Vasconcellos Larissa Bruscky Bruno Valdigem Haissa Assad Fernanda Fortuna

Introduction

According to current guidelines (class I recommendation), the treatment of heart failure with reduced ejection fraction (HFrEF) – defined as left ventricular ejection fraction (LVEF) ≤40% – should be based on the quadruple therapy scheme aimed at reducing cardiovascular outcomes. This regimen consists of beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), renin–angiotensin–aldosterone system blockers (including angiotensin-converting enzyme inhibitors [ACEIs], Angiotensin II Receptor Blockers [ARBs], or Angiotensin Receptor–Neprilysin Inhibitors [ARNIs]), and Sodium–Glucose Cotransporter-2 Inhibitors (SGLT2i).^,

In recent decades, with the therapeutic evolution of HFrEF, some medications such as digitalis,¹ once widely recommended, have been relegated to the role of adjuvants for refractory patients. These drugs lost prominence due to their adverse effects and the unequivocal benefits of the “Fantastic Four,” especially from the late 1990s onward (). However, in light of recent evidence,³ digitalis appear to be regaining relevance as an additional treatment option for Heart Failure (HF), reflecting that, given the constant nuances in the use of digitalis over the years, medicine is indeed the science of provisional truths.

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ABCHF

Viewpoint

Digoxin in Heart Failure with Reduced Ejection Fraction: A Proposal for a Practical Precision Medicine-Based Guide

Germano Emílio Conceição-Souza

Introduction: the paradox of digitalis therapy

Digoxin holds a unique position in the history of cardiovascular medicine. Although it is the oldest drug in continuous use for heart failure (HF) treatment, there has been a sharp decline in prescriptions over the past two decades. Overshadowed by the advent of disease-modifying therapies and stigmatized due to concerns regarding toxicity, digoxin was relegated to a Class IIa recommendation in the Brazilian guideline and a third-line recommendation (Class IIb) in the major international guidelines.^,

Nonetheless, the systematic exclusion of digoxin may represent a historical error based on incomplete interpretations of old data. In a scenario where heart failure with reduced ejection fraction (HFrEF) still imposes high morbidity, mortality, and residual symptoms despite optimized therapy, the premise of this viewpoint is unequivocal: digoxin is not obsolete; what has become obsolete is the empirical fixed-dose prescription model. In light of contemporary evidence, we propose a revival of digitalis therapy guided by precision medicine.

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ABC

Research Letter

New Insights into Medical Therapy for Heart Failure with Preserved Ejection Fraction

Eduardo Thadeu de Oliveira Correia et al. Evandro Tinoco Mesquita

Introduction

Heart failure (HF) phenotypes can be divided into categories according to the left ventricular ejection fraction (EF) – HF with preserved EF (HFpEF; EF ≥ 50%); HF with mildly reduced EF (HFmrEF; EF 41-49%) and HF with reduced EF (HFrEF; EF ≤ 40%). However, HF phenotypes differ beyond just a different EF. While HFpEF develops from an interplay of comorbidities that lead to structural heart disease and HF symptoms, HFrEF usually develops due to a cardiac insult that reduces cardiac output.^, Moreover, while multiple therapies can improve the prognosis of HFrEF, only sodium-glucose cotransporter 2 inhibitors (SGLT2i) improved outcomes in HFpEF in a randomized controlled trial (RCT). In this letter, we explore evidence for medical therapies that could benefit HFpEF patients.

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ABC

Research Letter

Heart Failure with Mildly Reduced Ejection Fraction: Therapeutical Considerations and Reasons for This Renaming

Eduardo Thadeu de Oliveira Correia et al. Evandro Tinoco Mesquita

Introduction

Heart failure (HF) has been classically divided into HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, to better classify HF patients with a left ventricular ejection fraction (LVEF) between 41 and 49%, previous guidelines have introduced the term HF with mid-range ejection fraction. Nonetheless, shortly after its formal introduction, HF with mid-range ejection fraction is now called HF with mildly reduced ejection fraction (HFmrEF). In this letter, we explore the reasons behind this renaming and why this change is more important than it may seem.

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ABCHF

Viewpoint

Clinical Profile-Based Pharmacological Sequencing for Heart Failure with Preserved Ejection Fraction

Evandro Tinoco Mesquita et al. Eduardo Thadeu de Oliveira Correia Letícia Mara dos Santos Barbetta

Introduction

Heart failure (HF) is classically categorized into phenotypes according to left ventricular ejection fraction (EF), one of them being HF with preserved EF (HFpEF; EF ≥ 50%). In the past decades, a myriad of drug therapies that reduce mortality and hospitalization rates for HF with reduced EF have emerged. However, although HFpEF accounts for about 50% of HF cases, to this date, only empagliflozin was shown to reduce HF hospitalization, and no drug reduced the risk for cardiovascular death in randomized clinical trials (RCTs). One hypothesis that may explain the lack of therapies that reduce hard outcomes in HFpEF is the variety of phenotypes that constitute HFpEF as a syndrome. Thus, in this paper, we discuss evidence from RCTs and post-hoc analyses of RCTs that may help improve HFpEF outcomes, aid clinicians, and pave the way for future RCTs.

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ABCHF

Research Letter

Personalized Treatment of Heart Failure with Reduced Ejection Fraction: Ivabradine, Nitrate/Hydralazine, and Digoxin – A Systematic Review and Meta-Analysis

Ivna Girard Cunha Vieira Lima et al. Edimar Alcides Bocchi

Introduction

In the last 30 years, treatment of chronic heart failure with reduced ejection fraction (HFrEF) has evolved considerably, and a significant reduction was achieved in mortality over time and hospitalization rates for chronic heart failure (CHF).

Neurohormonal blockade has become key in the treatment of CHF, but with the discovery of new therapies such as sodium-glucose cotransporter-2 inhibitors (SGLT2i), neprilysin inhibitors, resynchronization therapies, and new procedures, the number of treatment options in addition to standard therapy has increased considerably. However, it is known that the start of medications that reduce outcomes in CHF has historically been recommended following the order of publication of efficacy trials. Considering the many treatment options available today, a clinical question arises: is it possible to personalize additional treatments according to the patient’s clinical characteristics? This meta-analysis aims to look for populations of interest where ivabradine, hydralazine and nitrate, and digoxin could have incremental beneficial effects.

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ABC

Artigo Original

Optimized treatment and heart rate reduction in chronic heart failure

Irineu Blanco Moreno et al. Carlos Henrique Del Carlo Antônio Carlos Pereira-Barretto

BACKGROUND: Heart failure (HF) is a syndrome that leads to poor outcome in advanced forms. The neurohormonal blockade modifies this natural history; however, it is often suboptimal. OBJECTIVE: The aim of this study is to assess at what percentage cardiologists used to treating HF can prescribe target doses of drugs of proven efficacy. METHODS: A total of 104 outpatients with systolic dysfunction were consecutively enrolled, all under stabilized treatment. Demographic and treatment data were evaluated and the doses achieved were verified. The findings are shown as percentages and correlations are made between different variables. RESULTS: The mean age of patients was 64.1 ± 14.2 years, with SBP =115.4 ± 15.3, HR = 67.8 ± 9.4 bpm, weight = 76.0 ± 17.0 kg and sinus rhythm (90.4%). As for treatment, 93.3% received a RAS blocker (ACEI 52.9%), all received beta-blockers (BB), the most often prescribed being carvedilol (92.3%). As for the doses: 97.1% of those receiving an ARB were below the optimal dose and of those who received ACEI, 52.7% received an optimized dose. As for the BB, target doses were prescribed to 76.0% of them. In this group of patients, most with BB target dose, it can be seen that 36.5% had HR > 70 bpm in sinus rhythm. CONCLUSION: Cardiologists used to treating HF can prescribe target doses of ACEI and BB to most patients. Even though they receive the recommended doses, about one third of patients persists with HR > 70 bpm and should have their treatment optimized.

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ABC

Atualização

Digoxin: the results of the DIG study in the XXI century

Izo Helber et al. Paulo J. F. Tucci

After the report that there was no statistical significance in the general mortality of the DIG study, the indication of digoxin in the treatment regimens for congestive heart failure (CHF) drastically decreased. Post hoc studies that reassessed the DIG study data, indicated that an aspect that was not considered in this multicenter study has a critical influence on the prognosis of patients: the serum levels of digoxin. Regarding those that received a placebo, the general mortality and hospitalization were decreased in patients with a digoxin level < 0.9 ng/ml. At the first study that assessed the influence of digitalis in an experimental model of CHF, we verified in our lab that female rats with congestive syndrome secondary to myocardial infarction have a prolonged survival when undergoing treatment with digitoxin. The current information recommends that the merits of digoxin continue to be analyzed in order to adequately establish its importance in the treatment of CHF.

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ABC

Artigo Original

Use of digoxin in elderly patients admitted to a geriatric unit of a general hospital

Ulisses Gabriel de Vasconcelos Cunha et al. Maira Tonidandel Barbosa Emylucy Martins Paiva Paradela Flávio Gomes Carvalho

PURPOSE: To determine the prevalence of digoxin use as well as its indications in elderly patients at the time of admission to a geriatric unit of a general hospital. METHODS: One hundred and thirty elderly patients aged 65 and over (mean age = 80±9 years), 100 women and 30 men were consecutively investigated. Each patient was submitted to a thorough clinical investigation, laboratory work-up, chest X-ray, electrocardiogram and doppler echocardiogram. The use of digoxin was considered appropriate, questionable or inappropriate. RESULTS: At the time of admission to the geriatric unit 27.6% of the patients were receiving digoxin. The indication was considered appropriate in 36.1%, questionable in 11,1% and inappropriate in 52.7%. CONCLUSION: We found a high prevalence of digoxin use in elderly patients admitted to a geriatric unit of a general hospital. In most cases its indications were considered inappropriate or questionable. Due to the increased risk of digitalis intoxication in this age group the drug should be prescribed under more strict indications.

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