Eplerenone May Improve Cardiovascular Disease Risk in HIV
Mineralocorticoid receptor antagonism with eplerenone was well-tolerated in the HIV population with no significant changes in blood pressure or potassium.
A treatment approach targeting mineralocorticoid receptor (MR) blockade may improve select parameters related to inflammation, lipids, and ectopic fat in patients with HIV, according to new research published in the Journal of Clinical Endocrinology & Metabolism.
Even in patients with HIV with good virologic control, insulin resistance, changes in body composition and with ectopic fat accumulation and chronic inflammation are leading contributors to cardiovascular morbidity and mortality in this population. In this study, the effects of eplerenone, a steroidal anti-mineralocorticoid, were investigated for insulin sensitivity, inflammatory indices, and other metabolic parameters in individuals with HIV.
A total of 46 patients were randomly assigned to receive either eplerenone (doses were started at 25 mg/day for 1 week and escalated to 50 mg/day for the rest of the 6-month study period) or placebo. The primary end point was insulin-stimulated glucose uptake as measured by the euglycemic hyperinsulinemic clamp technique, and secondary end points included measures of body composition and metabolic indices.
Treatment with eplerenone did not significantly change insulin sensitivity normalized to insulin and lean body mass compared with placebo (0.48; interquartile range [IQR], -1.28 to 1.48 vs 0.43; IQR, 1.95 to 2.55 mg/min per µ/mL; P =.71). There were also no significant differences between groups in visceral adipose tissue (−11; IQR, −27 to 10 vs −2; IQR, −20 to 36 cm2; P =.42) or intrahepatic lipid (−1%; IQR, −3 to 2 vs 0%; IQR, −4 to 0 cm2; P =.51). However, use of eplerenone vs placebo significantly reduced intromyocellular lipids (−0.1%; IQR, −0.3 to 0.1 vs 0.0%; IQR, −0.1 to 0.2; P =.04).
Monocyte chemoattractant protein-1 (P =.04), and high-density lipoprotein (P =.04) also improved in the eplerenone group, and trends toward decreases in IL-6 (P =.10) and high sensitivity C-reactive protein (P =.10) were also observed.
The investigators concluded that while “eplerenone does not have adverse or beneficial effects on insulin sensitivity in HIV-infected individuals with mild abnormalities in glucose homeostasis, it may nonetheless be useful to improve CVD [cardiovascular disease] risk based on inflammatory, ectopic fat, and lipid levels.” But as the clinical significance of the magnitude of these improvements is yet unclear, “further studies of eplerenone are merited to determine the full scope of its effects in HIV,” they wrote.
Srinivasa S, Fitch KV, Wong K, et al. Randomized, placebo-controlled trial to evaluate effects of eplerenone on metabolic and inflammatory indices in HIV [published online April 5, 2018]. J Clin Endocrinol Metab. doi:10.1210/jc.2018-00330