Effects of SGLT2 Inhibition on Coronary Flow Reserve and Other Key Indices Relevant to Type 2 Myocardial Infarction Risk among Women with HIV

7. Project Summary/Abstract US women living with HIV (WLHIV) on antiretroviral therapy (ART) face a three-fold risk of myocardial infarction (MI) compared with women without HIV. Further, among WLHIV who present with MI, the majority (56%) present with type 2 MI – oxygen supply/demand mismatch in the absence of atherothrombosis. Data

suggest that coronary microvascular dysfunction and excess epicardial adipose tissue (EAT) volume represent salient processes relevant to type 2 MI risk among WLHIV. Our team aims to identify novel salutary interventions. We propose a randomized controlled trial assessing the effect of sodium glucose transporter 2

(SGLT2) inhibitors on cardiac PET-derived coronary flow reserve (a CV risk surrogate reflecting the ability to augment blood flow through large and small coronary arteries) and cardiac CT-derived EAT among WLHIV. SGLT2 inhibitors, originally developed to treat DM2, work by blocking renal sodium/glucose reabsorption,

leading to glucosuria, as well as reduced glomerular perfusion pressure. Kidney- and cardio-protective effects of SGLT2 inhibitors led to approval for use in CKD and heart failure, even among those without DM2. SGLT2 inhibition has been shown to improve coronary flow reserve and EAT in some patient populations but not

others. The observation that effects are population-specific highlights the need for testing among at-risk WLHIV. Notably, newly published work from our group suggests SGLT2 inhibitors are rarely prescribed to PLHIV with clinical indications in a large US healthcare system: