The Prospective comparison of Angiotensin Receptor-neprilysin inhibitor (ARNI) with Angiotensin converting enzyme inhibitor (ACEI) to Determine Impact on Global Mortality and morbidity in Heart Failure (HF) trial (PARADIGM-HF) showed that adding a neprilysin inhibitor (sacubitril) to a renin-angiotensin system blocker (and other standard therapy) reduced morbidity and mortality in ambulatory patients with chronic HF with reduced ejection fraction (HFrEF).
Heart failure is a complex clinical syndrome involving a multitude of neurohormonal pathways including the renin-angiotensin-aldosterone system, sympathetic nervous system, and natriuretic peptides system.
Moreover, while renin-angiotensin-aldosterone system inhibitors (RAASIs) represent the most cardio-nephro-protective drugs used in clinical practice, the treatment with these drugs per se increases serum potassium (sK) values, particularly when heart failure and diabetes mellitus coexist.
We discuss the complex interplay of kidney function and heart failure in the presence of renin-angiotensin-aldosterone system agents and suggest a clinical algorithm for management of acute decline in kidney function.
The new pharmacological class of angiotensin (Ang) receptor-neprilysin inhibitors (ARNI) prompted a real conceptual change in the treatment of HF moving from only the inhibition of the renin-Ang-aldosterone system and sympathetic nervous system to a strategy based on the concomitant pharmacological enhancement of endogenous natriuretic peptides.
In addition, we discuss the relevant molecular mechanisms that suggest BNP is protective against chronic kidney diseases and heart failure, especially in terms of the counterparts of the renin-angiotensin-aldosterone system (RAAS).
Excessive activation of the renin-angiotensin system (RAS) in diabetic cardiomyopathy (DCM) provokes a series of structural and functional abnormalities, and causes ventricular remodeling and heart failure in diabetes.
In summary, the normalization of plasma renin activity retards the progression of experimental HF by improving cardiac systolic function, reducing the development of systemic edema, cachexia/sarcopenia, and mortality.
This has been heralded as a step toward filling a crucial gap in HF management by providing strong evidence that combined inhibition of the angiotensin receptor and neprilysin is superior to inhibition of the renin-angiotensin system alone in stable patients with chronic HF as it negates the deleterious effects of angiotensin while concomitantly augmenting the beneficial effects of the endogenous natriuretic peptide system.
Although renin-angiotensin aldosterone system (RAAS) inhibitors have become the mainstay treatment for patients with chronic diseases, hyperkalemia is a major contributory deterrent to their use in patients with chronic kidney disease (CKD) and heart failure.
The results of this study provide a rationale for pharmacological therapies or posttranslational regulation therapies targeting genes expressed differentially in the renin-angiotensin system to remedy structural remodeling associated with atrial enlargement and heart failure progression in patients with MR.
The renin-angiotensin system (RAS), which plays an important role in the progression of heart failure, is efficiently blocked by the inhibition of renin, the rate-limiting enzyme in the RAS cascade.
Hyperkalemia (HK) occurs often among patients with chronic kidney disease (CKD) and heart failure (HF) and those treated with renin-angiotensin-aldosterone system inhibitors (RAASI).
Finally, half of the patients in all three age groups with heart failure and kidney disease received treatment with renin-angiotensin-system inhibitors; about two out of five patients received beta-blockers, while prescription rates of aldosterone inhibitors were low.
Although clinical trials have shown that the plasma renin-angiotensin system (RAS) activation decreases HF functional status and increases hospitalization for HF patients, the effect of intrarenal RAS activity is still unknown.
Association of Renin-Angiotensin Inhibitor Treatment With Mortality and Heart Failure Readmission in Patients With Transcatheter Aortic Valve Replacement.
As the most widely studied and commonly applied natriuretic peptide (NP), B-type natriuretic peptide (BNP) has the effects of diuresis, natriuresis, vasodilation, anti-hypertrophy, and anti-fibrosis and it inhibits the renin-angiotensin-aldosterone and sympathetic nervous systems to maintain cardiorenal homeostasis and counteract the effects of HF.
The cardiac release of NPs ANP and BNP represents an important compensatory mechanism during acute and chronic cardiac overload and during the pathogenesis of heart failure where their actions counteract the sustained activation of renin-angiotensin-aldosterone and other neurohormonal systems.
Although some conventional drugs, such as β-blockers and renin-angiotensin-aldosterone system (RAAS) inhibitors, have been shown to alleviate cardiac fibrosis in clinical trials, these traditional therapies do not tend to target all the fibrosis-associated mechanisms, and do not hamper the progression of cardiac fibrosis in patients with heart failure.
Beta-blockers and inhibitors of the renin-angiotensin aldosterone system improve survival and reduce morbidity in people with heart failure with reduced left ventricular ejection fraction.