An update of the blockade of the renin angiotensin aldosterone system in clinical practice

Abstract

Introduction: Cardiovascular disease (CVD) is the leading cause of death worldwide. Blockade of this system is commonly used in the treatment of cardiovascular (CV) and renal disease.

Areas covered: Data from multiple clinical trials have provided good evidence about the benefit of blocking the system as a therapeutic target to reduce CV and renal events. We have reviewed all the tested combinations of different drugs counteracting the effects of the renin–angiotensin–aldosterone system.

Expert opinion: Monotherapy with an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin II receptor blocker (ARB) remains valid in all the guidelines, whereas their dual combination has been discarded due to the absence of proven benefits in high CV risk patients and in patients with chronic kidney disease (CKD). The combination of the standard therapy with an ACEi or an ARB with a mineralocorticoid receptor blocker is a valid option, but has the inconvenience of frequent hyperkalemia in patients with CKD. Similarly, the addition of the direct renin inhibitor, aliskiren, to this standard therapy is not particularly supported in diabetic patients. New dual-acting blockers, for example, those combining valsartan and neprilysin inhibitors (LCZ696-Novartis) or endothelin converting enzyme inhibitors and neprilysin inhibitors (ECEI, Daglutril-Solvay), are currently under investigation.

Keywords:

• aldosterone antagononists
• angiotensin converting enzyme inhibitors
• angiotensin receptor blockers
• arterial hypertension
• cardiovascular disease
• chronic kidney disease
• combination of rennin–angiotensin–aldosterone blockers
• heart failure
• renin inhibitor

Acknowledgment

The authors thank the Instituto de Salud Carlos III (PI11/02432, PIE13/00045, PI13/01746, PI14/01841, CP15/00129), Fundación Mutua Madrileña, Fundación Eugenio Rodríguez Pascual and Fondos FEDER. DF Márquez and G Ruiz-Hurtado contributed equally to this work.

Declaration of interest

LM Ruilope has served as advisor for Astra-Zeneca, Bayer, Daiichi-Sankyo, Medtronic, Novartis, Relypsa and payment for development of educational presentations from Astra-Zeneca, Bayer, Daiichi-Sankyo, Medtronic, Novartis, Relypsa, Esteve and Takeda. 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.

Notes

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