Low dose‐eplerenone treatment decreases aortic stiffness in patients with resistant hypertension

Abstract

Vascular damage is aggravated in animal models of hypertension with mineralocorticoid (MR) excess and in hypertensive patients with primary hyperaldosteronism. MR antagonism has shown to provide effective blood pressure (BP)‐control in patients with treatment resistant hypertension (TRH), but the concurrent effects on the vasculature have not been examined. In a randomized, double‐blinded, placebo‐controlled parallel‐group study, 51 patients with TRH received either eplerenone 50 mg or placebo for 6 months together with additional antihypertensives titrated to achieve a BP target of <140/90 mm Hg. Pulse wave velocity (PWV), augmentation index (AIx), augmentation pressure (AP), AP normalized to a heart rate of 75/min (AP@HR75), renal resistive index (RRI), intima‐media thickness (IMT) and urinary albumin excretion rate (UAER) were assessed before and after treatment. PWV was reduced only with eplerenone (from 11.3±3.6 to 9.8±2.6 m/s, P˂.001), but not with placebo (10.3±2.0 to 10.1±1.8 m/s, P=.60), despite similar reductions in BP (−35±20/−15±11 mm Hg vs −30±19/−13±7 mm Hg, n.s.). Further, reductions in AP and AP@HR75 were greater with eplerenone, while changes in AIx, RRI, IMT and UAER were similar. Our data show that eplerenone beneficially affects markers of arterial stiffness and wave reflection in patients with TRH, independently of BP lowering. These data add to the evidence that MR antagonism should be the preferred treatment option in TRH.

Eplerenone improves endothelial function and arterial stiffness and inhibits Rho-associated kinase activity in patients with idiopathic hyperaldosteronism

“…It is likely that change in SBP with eplerenone treatment contributes to the decrease in PWV. There is a discrepancy between the effect of miner-alocorticoid receptor antagonists on arterial stiffness in patients with IHA and the results of our study and that previous study [33]. Some possible reasons for the discrepancy are postulated.…”

“…In contrast, medical treatment with spironolactone did not improve PWV in patients with primary aldosteronism, including IHA and an unknown subtype of primary aldosteronism. Kalizki et al [33] reported that treatment with eplerenone decreased PWV in patients with resistant hypertension. However, the effect of eplerenone on arterial stiffness in patients with IHA is unclear.…”

Spironolactone is superior to hydrochlorothiazide for blood pressure control and arterial stiffness improvement

“…In contrast, besides lowering BP, aldosterone antagonist has documented pleiotropic effects including improving endothelial function, anti-inflammation and antifibrosis. [ 21 – 23 ] Therefore, one may anticipate that spironolactone treatment would be better than HCTZ for arterial stiffness improvement and BP control. Results from the present study support this hypothesis.…”

Atherosclerotic Burden and Arterial Stiffness are Not Increased in Patients with Milder Forms of Primary Aldosteronism Compared to Patients with Essential Hypertension

“…Improvement of cPWV under treatment, as documented at follow-up in a small subset of PA patients in our study, may be a hint on the effect of aldosterone excess on vascular aging via arterial stiffening. Although it is of note that the reduction of cPWV and albuminuria have also been reported in patients with (essential) hypertension on MRA treatment, which should promote a more liberal use of MRA in patients with arterial hypertension [32,33].…”