Reducing Arterial Inflammation Using Eplerenone and Statins in HIV

Heart disease remains one of the principal causes of morbidity and mortality among the well-treated HIV population. Heart disease is on the rise in HIV, quickly advancing as a predominant source of death in HIV and is a key focus of longitudinal HIV clinical care for which we have few recognized prevention or treatment strategies. While the HIV population can achieve good virologic control with the use of contemporary antiretroviral therapies (ART), they have a higher burden of heart disease and other metabolic complications compared to the general population. Recently, we learned that statins can reduce the number of cardiovascular events among persons with HIV (PWH) by 36%. However, ART and statins do not mitigate this risk of heart disease completely among PWH. Even among those treated adequately with ART and statins, 39% still remain at risk for a cardiovascular event. Despite goal-directed treatment with ART and statins, there remains untreated inflammation, which may account for this residual risk. We have previously shown unique physiology, such that elevations in a hormone called aldosterone are associated with increased inflammation in the vasculature among PWH. We then tested a medication known to block aldosterone, called eplerenone, which in a class of medications called mineralocorticoid receptor blockers, on inflammation in the vasculature among PWH who were not treated with statin medication and saw a robust decrease in arterial inflammation. Currently, there are no medication to help reduce inflammatory-mediated heart disease in HIV. In this way, it may be that the addition of eplerenone to statin therapy could further mitigate heart disease risk and augment statin therapy as the standard of care for primary prevention. Moreover, we know that inflammation in the vasculature may be associated with the development of non-calcified plaque, a type of plaque that is highly inflamed and prone to rupture and cause a heart attack. Overall, the population with HIV can be used as a paradigm and model to understand inflammatory sequelae in other highly metabolic populations, and findings from these studies could have applications to those other groups, such as those with obesity.

The main objectives of this study are to test whether addition of the medication eplerenone to background statins may reduce residual arterial inflammation further among PWH. We will further understand a potential mechanism by which arterial inflammation is linked to heart disease by evaluating changes over time in non-calcified plaque. Eplerenone is an oral medication taken twice daily and is FDA approved for treatment of hypertension and heart failure with reduced ejection fraction following myocardial infarction, and we are evaluating whether this medication could be useful to improve inflammatory-mediated heart disease and overall inflammation in HIV. This is a multi-site (MGH/UCLA), 12 month randomized placebo-controlled study among ART- and statin-treated PWH with baseline arterial inflammation to study the effects of MRA vs. placebo as add-on to standard of care moderate-intensity statin on arterial inflammation.