eplerenone and Coronary-Vasospasm

Mineralocorticoid receptor antagonists are increasingly used in patients with treatment-resistant hypertension (TRH). There is experimental evidence for blood pressure (BP) independent effects of mineralocorticoid receptor blockade on cardiovascular target organ damage. We hypothesized that low-dose eplerenone (50 mg) will reduce left ventricular mass (LVM) beyond its BP-lowering effects.. We performed a randomized, double-blind, placebo-controlled, parallel group study in 51 patients with TRH. Patients were allocated to receive either eplerenone 50 mg or placebo for 6 months, while other antihypertensive agents could be added in both groups to achieve a BP target of less than 140/90 mmHg. LVM was assessed by MRI before and after treatment.. Baseline office BP was similar in the eplerenone and the placebo group (166 ± 21/91 ± 15 versus 159 ± 19/94 ± 8 mmHg, n.s.). BP was similarly reduced in the eplerenone versus the placebo group (-35 ± 20/-15 ± 11 versus -30 ± 19/-13 ± 7 mmHg, n.s.). However, LVM was reduced only in the eplerenone group (from 155 ± 33 to 136 ± 33 g, P < 0.001), but not in the placebo group (152 ± 32 versus 148 ± 38 g, P = 0.45).. Despite similar BP-lowering, only patients with TRH who were allocated to eplerenone experienced a reduction of LVM. Thus, our data suggest that in patients with TRH, mineralocorticoid receptor antagonists should be used preferentially in order to achieve an effective reduction of LVM along with the improvement of BP control.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Coronary Vasospasm; Double-Blind Method; Drug Therapy, Combination; Eplerenone; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Magnetic Resonance Imaging; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Spironolactone

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.

Topics: Aged; Blood Pressure Determination; Carotid Intima-Media Thickness; Coronary Vasospasm; Double-Blind Method; Eplerenone; Female; Humans; Hypertension; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Prospective Studies; Pulse Wave Analysis; Serum Albumin, Human; Spironolactone; Vascular Stiffness