Use of Eplerenone potential strategy to reduce arterial inflammation among persons with HIV: JAMA

“Mineralocorticoid receptor antagonism by Eplerenone may be a potential strategy to reduce arterial inflammation in HIV patients,” the researchers wrote in their study published in JAMA Cardiology.

People with HIV are 1.5 to 2 times more likely to be affected by cardiovascular disease. This increased burden of heart disease may be driven by Chronic systemic and local inflammation that persists among PWH taking antiretroviral therapy (ART).

Previous studies have shown increased renin-angiotensin-aldosterone system (RAAS) activation among HIV patients in association with increased markers of arterial inflammation. Therefore, RAAS activation may be a potential novel target for CVD prevention in HIV.

In the MIRACLE HIV trial, Eplerenone improved myocardial perfusion indices. In the MIRABELLA HIV substudy of MIRACLE HIV, Suman Srinivasa, Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues hypothesized that RAAS blockade using mineralocorticoid receptor antagonism would reduce arterial inflammation among HIV patients assessed by 18F-fludeoxyglucose–positron emission tomography/computed tomography (18F-FDG PET/CT).

They aimed to investigate the effects of eplerenone on arterial inflammation among well-treated PWH without known CVD. Participants were enrolled in the MIRABELLA study and underwent additional 18F-FDG PET/CT imaging of the aorta and carotid arteries to assess arterial inflammation over 12 months of treatment with eplerenone vs placebo.

The study’s main outcome was a change in the target-to-background ratio (TBR), a measure of arterial wall inflammation, following 12 months of treatment. The index vessel was defined as the vessel (left carotid artery, aorta, or right carotid artery) with the highest TBR at baseline in each participant.

Twenty-six participants (mean age, 54 years; 69% males) were randomized to Eplerenone, 50 mg, twice a day (n=13) versus identical placebo (n=13). Treatment groups were of similar age, body mass index, and sex.

The study led to the following findings:

• Eplerenone was associated with a reduction in TBR of the primary endpoint, the index vessel (eplerenone vs placebo: model treatment effect, −0.31; percentage change, −12.4% versus 5.1%).
• There was a significant reduction of the TBR of the index vessel’s most diseased segment (MDS) (eplerenone vs placebo: −19.1% versus 6.8%).
• A similar result was seen assessing the index vessel of the carotids (eplerenone vs placebo: −10.0% versus 9.7%).
• Reduction in the TBR of MDS of the index vessel on 18F-FDG PET/CT correlated with improvement in the stress myocardial blood flow on cardiac magnetic resonance imaging (Spearman ρ = −0.67).

“The findings showed that eplerenone was associated with reduced arterial inflammation among well-treated PWH without known CVD,” the researchers wrote. They added, “Reductions in arterial inflammation as measured by 18F-FDG PET/CT were related to improvements in stress myocardial perfusion.”

‘Further larger studies should explore whether eplerenone is a potential treatment strategy for inflammatory-mediated CVD in persons with HIV,” they concluded.

Reference:

Srinivasa S, Abohashem S, Walpert AR, et al. Mineralocorticoid Receptor Antagonism by Eplerenone and Arterial Inflammation in HIV: The MIRABELLA HIV Study. JAMA Cardiol. Published online December 13, 2023. doi:10.1001/jamacardio.2023.4578