Renin–angiotensin–aldosterone system blockade for cardiovascular diseases: current status

Abstract

Activation of the renin-angiotensin-aldosterone system (RAAS) results in vasoconstriction, muscular (vascular and cardiac) hypertrophy and fibrosis. Established arterial stiffness and cardiac dysfunction are key factors contributing to subsequent cardiovascular and renal complications. Blockade of RAAS has been shown to be beneficial in patients with hypertension, acute myocardial infarction, chronic systolic heart failure, stroke and diabetic renal disease. An aggressive approach for more extensive RAAS blockade with combination of two commonly used RAAS blockers [ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)] yielded conflicting results in different patient populations. Combination therapy is also associated with more side effects, in particular hypotension, hyperkalaemia and renal impairment. Recently published ONTARGET study showed ACEI/ARB combination therapy was associated with more adverse effects without any increase in benefit. The Canadian Hypertension Education Program responded with a new warning: 'Do not use ACEI and ARB in combination'. However, the European Society of Cardiology in their updated heart failure treatment guidelines still recommended ACEI/ARB combo as a viable option. This apparent inconsistency among guidelines generates debate as to which approach of RAAS inhibition is the best. The current paper reviews the latest evidence of isolated ACEI or ARB use and their combination in cardiovascular diseases, and makes recommendations for their prescriptions in specific patient populations.

Different actions of losartan and ramipril on adipose tissue activity and vascular remodeling biomarkers in hypertensive patients

“…8 From a metabolic point of view, drugs interacting with the RAAS are usually defined as neutral in the sense that, contrary to b-blockers and thiazides, these drugs do not negatively interact with lipid and glucose metabolism. 9 However, some AT1R blockers could have positive metabolic effects because of a mild activating action on nuclear peroxisome proliferator-activated receptors. [10][11][12] On the other hand, it is not yet clear whether angiotensin-converting enzyme inhibition or AT1R blockade have some action on adipokine metabolism.…”

The renin-angiotensin system meets the hallmarks of cancer

“…38 The use of this group of drugs has two potential benefits. First, the use of RAS blockers could improve the prognosis of the patients, and second, the finding of a new therapeutic use for a proven drug has the advantage of decreased development costs and decreased time to market compared to traditional discovery efforts because of the availability of previously collected pharmacokinetic, toxicology and safety data.…”

The angiotensin II type 2 receptor agonist Compound 21 is protective in experimental diabetes-associated atherosclerosis

“…Overactivation of the renin-angiotensin system (RAS) is wellrecognised to be a major underlying pathological mechanism that drives the development of diabetic vascular disease, with its effector peptide, angiotensin II (Ang II), being the main mediator [1]. Pharmacological inhibition of the RAS by targeting either Ang II production with an angiotensinconverting enzyme inhibitor or the activity of Ang II with an angiotensin receptor blocker (ARB) remains first-line treatment for patients with diabetes and vascular disease [2].…”