Telmisartan Versus Enalapril in Heart Failure With Reduced Ejection Fraction Patients With Moderately Impaired Kidney Functions

Heart Failure (HF) poses a major health burden in various populations, with devastating annual rates of morbidity and mortality. It is estimated that 1%-to-2% of the general population suffer from the heart failure syndrome. HF with reduced ejection fraction (HFrEF) is the most studied among different strata of ejection fractions (compared to HFpEF and HFmrEF), and thus therapies with evidence based survival benefit are well identified. The syndrome of heart failure and the subsequent reduced cardiac output triggers activation of neurohormonal compensatory responses aiming to augment cardiac output and tissue perfusion, like upregulation of sympathetic nervous system and over-activation of the Renin Angiotensin Aldosterone System. Nevertheless, overshooting of such compensatory mechanisms have deleterious effects on heart failure in terms of aggravation of symptoms and reduction of survival. Angiotensin II acts primarily on type I receptors inducing the following: * intense arteriolar vasoconstriction * stimulates sodium reabsorption in the proximal convoluted tubules * stimulates adrenal medulla to secrete catecholamines * stimulates sympathetic nervous system, through facilitation of ganglionic stimulation * modestly inhibits vagus (parasympathetic system) * stimulates secretion of vasopressin/anti-diuretic hormone * stimulates adrenal cortex to secrete aldosterone, which promotes sodium and water reabsorption and promotes potassium secretion at the distal convoluted tubules in addition to induction of myocardial remodeling and fibrosis * constricts the glomerular efferent arteriole which increase filtration pressure and promotes proteinuria and nephron injury/loss. While, angiotensin type II receptors activation have beneficial effects like vasodilatation and promoting endothelial function. Accordingly, angiotensin converting enzyme inhibitors (ACEi), angiotensin-II receptor type I blockers (ARBs) or Angiotensin receptor blocker- neprilisin inhibitor (ARNI)