New Pharmacological Strategies in Chronic Heart Failure

Research, Society and Development

To evaluate, describe and compare the pharmacological treatments available for heart failure (HF). This is a literature review about the pharmacological treatment of HF based on articles selected from the PubMed database, as well as relevant guidelines, using pertinent keywords and application of inclusion and exclusion criteria. Chronic heart failure is a common condition that, if untreated, harms quality of life and is associated with a high risk of mortality, morbidity, and recurrent hospitalization. However, the prognosis of patients with this condition has been improved with knowledge of the pathophysiology of HF and, therefore, assertive application of both non-pharmacological and pharmacological treatment recommendations. Pharmacotherapy is based on neurohormoral inhibition of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system to improve the health status and survival of these patients. Currently, the recommendation for the treatment of HF with...

Revista Portuguesa de Cardiologia, 2019

The current paradigm of medical therapy for heart failure with reduced ejection fraction (HFrEF) is triple neurohormonal blockade with an angiotensin-converting enzyme inhibitor (ACEI), a beta-blocker (BB) and a mineralocorticoid receptor antagonist (MRA). However, three-year mortality remains over 30%. Stimulation of counter-regulatory systems in addition to neurohormonal blockade constitutes a new paradigm, termed neurohormonal modulation. Sacubitril/valsartan is the first element of this new strategy. PARADIGM-HF was the largest randomized clinical trial conducted in HFrEF. It included 8442 patients and compared the efficacy and safety of sacubitril/valsartan versus enalapril. The primary endpoint was the composite of cardiovascular mortality and hospitalization due to HF, which occurred in 914 (21.8%) patients receiving sacubitril/valsartan and in 1117 (26.5%

Postgraduate Medical Journal, 2003

Chronic heart failure is widely recognised as a common and escalating problem that causes major disability and often shortens life. Diuretics and digoxin have formed the mainstay of treatment for many years. Clinical trials have demonstrated that angiotensin converting enzymes and bblockers, in selected patients, improve symptoms and reduce mortality. Angiotensin-II antagonists and spironolactone may also have a role in certain individuals. Newer pharmacological approaches to the management of this complex disease are being developed, but await full evaluation.

South Asian research journal of biology and applied biosciences, 2022

Chronic heart failure refers to a clinical state of systemic and pulmonary congestion resulting from inability of the heart to pump as much blood as required for the adequate metabolism of the body. The commonest causes of heart failure are coronary artery disease, hypertension and diabetes, however, hypertension and diabetes have been found to be stronger risk factors in elderly women and coronary artery disease and smoking are stronger risk factors in elderly men. Pathophysiologically, heart failure is either an inadequate cardiac output for the organism's metabolic demands or an adequate cardiac output that is due to neurohormonal compensation, which means the inability of the heart to supply blood to the tissues according to their needs without additional strain. The pharmacological treatment of chronic heart failure with reduced ejection fraction is now based on four classes of drugs that have been proven to reduce mortality among heart failure patients such as angiotensinogen converting enzyme inhibitors or angiotensin II receptor blockers, beta-blockers, aldosterone antagonists and sodium-glucose co-transporter 2 inhibitors. Angiotensinogen converting enzyme inhibitors or angiotensin II receptor blocker therapy should be initiated at a low dose with very gradual up titration, monitoring renal function and serum potassium levels closely. Chronic heart failure treatment with direct inhibitors of aldosterone receptors brought about a significant improvement in terms of survival and hospitalizations.

Heart Failure Reviews, 2021

After initial strategies targeting inotropism and congestion, the neurohormonal interpretative model of heart failure (HF) pathophysiology has set the basis for current pharmacological management of HF, as most of guideline recommended drug classes, including beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists, blunt the activation of detrimental neurohormonal axes, namely sympathetic and renin–angiotensin–aldosterone (RAAS) systems. More recently, sacubitril/valsartan, a first-in-class angiotensin receptor neprilysin inhibitor, combining inhibition of RAAS and potentiation of the counter-regulatory natriuretic peptide system, has been consistently demonstrated to reduce mortality and HF-related hospitalization. A number of novel pharmacological approaches have been tested during the latest years, leading to mixed results. Among them, drugs acting directly at a second messenger level, such as the soluble ...

Italian heart journal : official journal of the Italian Federation of Cardiology, 2003

In the past 20 years, enormous progress has been made in the understanding of the pathophysiology and treatment of the complex clinical syndrome of heart failure. It has been a bidirectional process, with improvements in the understanding of the pathophysiology suggesting new therapeutic approaches and the success and failures of clinical trials refining our hypotheses or even suggesting the involvement of new pathophysiological mechanisms. In the past, heart failure was interpreted on the basis of a pathophysiological model according to which the hemodynamic abnormalities played a key role in determining the clinical presentation and the evolution of the disease. Therefore, the objective of pharmacological treatment was to improve these hemodynamic abnormalities. At the beginning of the '90s it became clear that the activation of the reninangiotensin-aldosterone system and of the sympathetic system caused by the abnormality in cardiac function had deleterious clinical effects i...

European Heart Journal, 2002

During the past 50 years there have been vast improvements in the treatment of chronic heart failure (CHF). CHF was initially considered to be a cardio-renal problem -an acute disorder leading to volume expansion and oedema. Diuretics and digitalis were the only available treatments. Subsequently, CHF was considered to be the result of both myocardial dysfunction and increased tone in the pulmonary and peripheral circulations. The presence of peripheral vasoconstriction suggested that circulatory failure was an important component of the disease, and vasodilators were added to therapy. In the more recent past, experimental and clinical studies have demonstrated that CHF is also characterized by increased neurohormonal activation. This has led to the use of angiotensin-converting enzyme inhibitors, beta-blockers and spirouolactone in CHF. Increased neurohormonal activity is now recognized as one of the major pathophysiological factors that contribute to the progression of CHF. Activation of neurohormonal mechanisms is only compensatory in the short term; chronic activation produces detrimental changes in the myocardkma, kidneys and peripheral vasculature. This article provides an overview of the key neurohormonal systems that are activated in CHF. (Eur Heart J Supplements 2002; 4 (Suppl D): D3-Dll)

Drugs, 2000

The American Journal of Cardiology, 2003

Heart failure (HF) is a complex clinical syndrome resulting from any structural or functional cardiac disorder impairing the ability of the ventricles to fill with or eject blood. The approach to pharmacologic treatment has become a combined preventive and symptomatic management strategy. Ideally, treatment should be initiated in patients at risk, preventing disease progression. In patients who have progressed to symptomatic left ventricular dysfunction, certain therapies have been demonstrated to improve survival, decrease hospitalizations, and reduce symptoms. The mainstay therapies are angiotensin-converting enzyme (ACE) inhibitors and ␤-blockers (bisoprolol, carvedilol, and metoprolol XL/ CR), with diuretics to control fluid balance. In patients who cannot tolerate ACE inhibitors because of angioedema or severe cough, valsartan can be substituted. Valsartan should not be added in patients already taking an ACE inhibitor and a ␤-blocker. Spironolactone is recommended in patients who have New York Heart Association (NYHA) class III to IV symptoms despite maximal therapies with ACE inhibitors, ␤-blockers, diuretics, and digoxin. Low-dose digoxin, yielding a serum concentration <1 ng/mL can be added to improve symptoms and, possibly, mortality. The combination of hydralazine and isosorbide dinitrate might be useful in patients (especially in African Americans) who cannot tolerate ACE inhibitors or valsartan because of hypotension or renal dysfunction. Calcium antagonists, with the exception of amlodipine, oral or intravenous inotropes, and vasodilators, should be avoided in HF with reduced systolic function. Amiodarone should be used only if patients have a family history of sudden death, or a history of ventricular fibrillation or sustained ventricular tachycardia, and should be used in conjunction with an implantable defibrillator. Finally, anticoagulation is recommended only in patients who have concomitant atrial fibrillation or a previous history of cerebral or systemic emboli. ᮊ2003 by Excerpta Medica, Inc.