A Microsimulation of Eligibility for Cardiorenal Combination Treatment and Potential Deaths Averted

Background: Clinical guidelines recommend combined use of renin-angiotensin system inhibitors (RASi), sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP1RA) and nonsteroidal mineralocorticoid receptor antagonists (nsMRA) to reduce cardiorenal risk. However, eligibility for combination treatment and the potential effects of implementation on preventing mortality remain unclear. Methods: We conducted a microsimulation study using data from the National Health and Nutrition Examination Survey (NHANES 2007–2016 and 2017–2020). The model incorporated acute treatment effects of RASi, SGLT2i, GLP1RA, and nsMRA on estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), and serum potassium. Eligibility for combination treatment was assessed for each participant according to 73 clinical practice guideline recommendations and inclusion criteria from recently published clinical trials. Primary outcomes included: 1) the percentage of participants eligible for single or combination treatment with RASi, SGLT2i, GLP1RA, and nsMRA, and 2) the projected potential number of annually averted all-cause and cardiovascular deaths. Results: Of 8,152 adults, 15% had type 2 diabetes (DM), 14% had chronic kidney disease (CKD) and 5% had DM and CKD (DKD). Among all U.S. adults, 19% were treated with RASi, 1% with SGLT2i, 1% with GLP1RA and none with nsMRA. The dual-therapy associated with the highest eligibility was RASi+SGLT2i, with 15% of the U.S. population eligible (DM subgroup: 70%; CKD subgroup: 50%; DKD subgroup: 84%). The triple-therapy with the highest eligibility was RASi+SGLT2i+GLP1RA, with 11% overall eligibility (DM: 69%; CKD: 33%; DKD: 83%). Eligibility for quadruple-therapy was 4% overall (DM: 22%; CKD: 17%; DKD: 40%). Based on our microsimulation model, fewer individuals with diabetes were eligible for triple-therapy with RASi+SGLT2i+GLP1RA compared to dual-therapy with RASi+SGLT2i, but triple-therapy was projected to prevent 2-fold more potential all-cause and cardiovascular deaths versus dual-therapy. Conclusions: Under the assumptions of our microsimulation model, eligibility for combined treatment with cardiorenal protective therapies was prevalent, particularly in adults with type 2 diabetes and/or CKD.