Should ACE inhibitors and ARBs be used in combination in children?

The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in a host of renal and cardiovascular functions. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), drugs that disrupt RAAS function, are effective in treating hypertension and offer other renoprotective effects independent of blood pressure (BP) reduction. As our understanding of RAAS physiology and the feedback mechanisms of ACE inhibition and angiotensin receptor blockade have improved, questions have been raised as to whether combination ACEI/ARB therapy is warranted in certain patients with incomplete angiotensin blockade on one agent. In this review, we discuss the rationale for combination ACEI/ARB therapy and summarize the results of key adult studies and the limited pediatric literature that have investigated this therapeutic approach. We additionally review novel therapies that have been developed over the past decade as alternative approaches to combination ACEI/ARB therapy, or that may be potentially used in combination with ACEIs or ARBs, in which further adult and pediatric studies are needed.