The incidence and implications of aldosterone breakthrough

Abstract

Interruption of the renin-angiotensin-aldosterone system has become a leading therapeutic strategy in the treatment of chronic heart and kidney disease. Angiotensin-converting-enzyme inhibitors and angiotensin-receptor blockers do not, however, uniformly suppress the renin-angiotensin-aldosterone system. Plasma aldosterone levels are elevated in a subset of patients despite therapy. This phenomenon, known as 'aldosterone escape' or 'aldosterone breakthrough', has only been directly examined in small numbers of patients. The key questions of how often breakthrough occurs and whether breakthrough leads to worse outcomes have yet to be definitively answered. In this Review, we summarize the reported data on the incidence and clinical implications of aldosterone breakthrough, and highlight areas of uncertainty that have yet to be adequately addressed in the literature. Although the available evidence is not strong enough to support widespread screening for aldosterone breakthrough, our findings should prompt physicians to consider the phenomenon in select patients as well as guide future research efforts.

A prospective, randomized, double‐blind, placebo‐controlled pilot study of sacubitril/valsartan (Entresto) in dogs with cardiomegaly secondary to myxomatous mitral valve disease

“…Angiotensin converting enzyme inhibitors are effective at decreasing plasma ACE activity but less so at decreasing tissue ACE activity, and most of the angiotensin II (ATII) production in tissues occurs via non‐ACE‐mediated pathways, rendering ACEI ineffective 5, 6, 7. The lack of effectiveness of ACEI to suppress ACE‐dependent and non‐ACE‐dependent tissue ATII production, along with local production of aldosterone, is thought to drive the phenomenon of aldosterone breakthrough (ABT) 8. Aldosterone breakthrough has been documented in multiple studies in dogs, with a prevalence of 32% in dogs with MMVD treated for CHF 9, 10, 11, 12, 13, 14.…”

Aplicaciones y proyecciones de los antagonistas del receptor de mineralocorticoides en el tratamiento de patologías cardiovasculares

“…Al comparar fármacos antihipertensivos de cuarta línea, un estudio cruzado prospectivo ha mostrado que los ARM tendrían un mayor efecto antihipertensivo en pacientes con HTAR en comparación al doble bloqueo de angiotensina II utilizando un ARA2 (-20,8 ± -14,6/-8,8 ±-7,3 vs -7,1 ± 13,4/-3,4 ± 6,2 mmHg respectivamente, n = 42) 62 . Estos resultados se explicarían debido a que los IECA/ ARA2 son incapaces de prevenir a largo plazo el aumento de concentración plasmática de aldosterona, fenómeno conocido como escape de aldosterona 63 .…”

Therapeutic Modalities in Diabetic Nephropathy: Standard and Emerging Approaches

“…[69][70][71] This partial response has been attributed in part to feedback effects, such as angiotensin-escape and aldosteroneescape. 72,73 In light of these phenomena, alternative approaches to optimize the RAAS-blockade are being sought. The activity of renin, the rate-limiting-step in the RAAS cascade, is increased when either ACEi or ARBS are used for prolonged periods.…”