The evolving landscape of RAAS inhibition: from ACE inhibitors to ARBs, to DRIs and beyond

Abstract

Chronic renin–angiotensin–aldosterone system (RAAS) activation has far-reaching effects on cardiometabolic risk and is a substantial contributor to cardiovascular (CV) disease and renal dysfunction. The vascular effects of sustained RAAS activation are associated with hemodynamic imbalances, as well as inflammatory stimulation and prothrombotic processes that lead to fibrosis, endothelial dysfunction and cellular remodeling. RAAS inhibition therapies, which include the use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and more recently, direct renin inhibitors, have been used in clinical practice for more than 30 years. Our understanding of how these drugs work, alone and in combination, has contributed to an expanding landscape of treatment options and established RAAS inhibition as essential for reducing the risk of CV and renal disease. This perspective provides a historical overview of how RAAS inhibitors have evolved to their present-day status and will discuss recently discovered functions for components of this complicated and powerful regulatory system.

Keywords::

• ACE inhibitor
• angiotensin receptor blocker
• direct renin inhibitor
• plasma renin activity
• (pro)renin receptor

Financial & competing interests disclosure

This work was supported in part by Boehringer Ingelheim Pharmaceuticals, Inc. The authors received no compensation related to the development of the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing and editorial assistance was provided by A Sherwood of Publication CONNEXION (Newtown, PA, USA), which was contracted by Boehringer Ingelheim Pharmaceuticals, Inc. for these services. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors, were fully responsible for all content and editorial decisions and were involved at all stages of manuscript development.