Blocking the RAAS at different levels: an update on the use of the direct renin inhibitors alone and in combination

Francesca Cagnoni¹, Christian Achiri Ngu Njwe¹, Augusto Zaninelli⁴, Alessandra Rossi Ricci¹, Diletta Daffra², Antonio D’Ospina¹, Paola Preti³, Maurizio Destro¹

¹Internal Medicine, Ospedale Unificato Broni-Stradella, Stradella (PV), Italy; ²Internal Medicine, S.S. Annunziata Hospital, Varzi (PV), Italy; ³Internal Medicine, University of Pavia, Pavia, Italy; ⁴School of Medicine, University of Florence, Florence, Italy

Abstract: The renin–angiotensin–aldosterone system (RAAS), an important regulator of blood pressure and mediator of hypertension-related complications, is a prime target for cardiovascular drug therapy. Angiotensin-converting enzyme inhibitors (ACEIs) were the first drugs to be used to block the RAAS. Angiotensin II receptor blockers (ARBs) have also been shown to be equally effective for treatment. Although these drugs are highly effective and are widely used in the management of hypertension, current treatment regimens with ACEIs and ARBs are unable to completely suppress the RAAS. Combinations of ACEIs and ARBs have been shown to be superior than to either agent alone for some, but certainly not all, composite cardiovascular and kidney outcomes, but dual RAAS blockade with the combination of an ACEI and an ARB is sometimes associated with an increase in the risk for adverse events, primarily hyperkalemia and worsening renal function. The recent introduction of the direct renin inhibitor, aliskiren, has made available new combination strategies to obtain a more complete blockade of the RAAS with fewer adverse events. Renin system blockade with aliskiren and another RAAS agent has been, and still is, the subject of many large-scale clinical trials and furthermore, is already available in some countries as a fixed combination.

Keywords: angiotensin II receptor blockers, renin–angiotensin–aldosterone system, hypertension, angiotensin-converting enzyme inhibitors