The mTOR-inhibitor everolimus reduces hypervolemia in patients with primary aldosteronism.

Abstract

Background: We recently showed in a proof-of-concept study that treating individuals with primary aldosteronism with the mTOR-inhibitor everolimus decreases home blood pressure and renin suppression overall, and markedly reduces aldosterone levels in a subset of individuals. Based on these findings, the question arose whether the effects of everolimus were also mediated via aldosterone-independent mechanisms. Here, we undertook an exploratory, secondary analysis of above-mentioned study to comprehensively investigate how everolimus impacted the hemodynamic status of the study participants, which in turn could elucidate these mechanisms.

Methods: Hemodynamic parameters were measured in study participants with primary aldosteronism at baseline, after treatment with everolimus 0.75 mg orally twice daily for 2 weeks and after a 2-week wash-out. Of the 14 participants, 10 participants had complete data sets for peripheral and central blood pressure, heart rate and pulse wave velocity, and 7 participants had complete data sets for cardiac index, inotropic state index, left stroke work index and stroke systemic vascular resistance index that could be analyzed. Parameters were acquired by brachial oscillometry (Mobil-o-graph PWA) and thoracic electrical bioimpedance (HOTMAN^® System).

Results: After treatment with everolimus, peripheral (P=0.049) and central (P=0.037) diastolic blood pressure, as well as hypervolemia (P=0.008) were significantly decreased. Likewise, peripheral (P=0.073) and central systolic blood pressure (P=0.166) trended downwards.

Conclusions: Everolimus lowers central and peripheral blood pressure in individuals with primary aldosteronism, possibly by decreasing primary aldosteronism-induced hypervolemia and preload.