RAAS inhibition and mortality in hypertension

Abstract

The renin-angiotensin-aldosterone system (RAAS) regulates the body's hemodynamic equilibrium, circulating volume, and electrolyte balance, and is a key therapeutic target in hypertension, the world's leading cause of premature mortality. Hypertensive disorders are strongly linked with an overactive RAAS, and RAAS inhibitors, like angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), are routinely used to treat high blood pressure (BP). BP reduction is one of the main goals of current European hypertension guidelines. Oral ACE inhibitors, the oldest category of RAAS inhibitor, were commercially released over 30 years ago in the early 1980s, over a decade before the first ARBs became available. The introduction of ACE inhibitors heralded major changes in the way hypertension and cardiovascular disease were treated. Although the decision of the medical community to replace older ACE inhibitors with more modern ARBs in the 1990s was debatable, it did nevertheless allow scientists to learn more about the angiotensin receptors involved in RAAS stimulation. This and much else of value have been discovered since RAAS inhibitors first became available, but some surprising gaps in our knowledge exist. Until recently, the effect of RAAS inhibition on mortality in hypertension was unknown. This question was recently addressed by a meta-analysis of randomized controlled trials in populations who received contemporary antihypertensive medication. The results of this meta-analysis have helped elucidate the long-term consequences of treatment with RAAS inhibitors on mortality in hypertension. This article will consider the differences between RAAS inhibitors in terms of pharmacological and clinical effects and analyze the impact of the main types of RAAS inhibitor, ACE inhibitors and ARBs, on mortality reduction in hypertensive patients with reference to this latest meta-analysis.

Renin-angiotensin-aldosterone System Blockers, Hypertension, and Clinical Outcomes

“…The advantages of Ang II reduction by ACE inhibition are substantial but may be compromised in the long term due to "Ang II and aldosterone escape." [6] Disrupted negative feedback mechanisms cause renin and Ang I concentrations to rise, eventually leading to Ang II escape when non-ACE enzymes such as chymase convert Ang I to Ang II. [6] Similarly, aldosterone escape occurs after longterm ACE inhibitor therapy.…”

Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on Prothrombotic Processes and Myocardial Infarction Risk

“…Ferrari and colleagues [26, 41] compared the mechanisms of action of the two groups of RAAS and their effects on endothelial and vascular functions in detail. They found several differences between the two groups in terms of factors that play a role in functional and structural changes of the vessels.…”

Drugs Targeting RAAS in the Treatment of Hypertension and Other Cardiovascular Diseases

“…ACE inhibitor-mediated disrupted negative feedback mechanism increases the levels of renin and subsequently of Ang I. In such a situation, non-ACE enzymes such as chymase can convert Ang I to Ang II, resulting in Ang II escape [ 139 ]. Therefore, compared to ACE inhibition, selective AT 1 receptor blockade might have distinct advantages, like the absence of angiotensin II escape and unopposed AT 2 receptormediated effects of Ang II, predominantly vasodilation.…”