Sanjay Rajagopalan, MD, Leads Clinical Trial Showing Mechanism of Benefit of Mineralocorticoid Receptor Antagonist for Patients with Type 2 Diabetes and Chronic Kidney Disease
October 13, 2024
Innovations in Cardiovascular Medicine & Surgery | October 2024
Results from the National Institutes of Health (NIH)-sponsored MAGMA (Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis) trial show that spironolactone (Aldactone) prevents aortic plaque progression and reduces left ventricular mass and fibrosis in patients with type 2 diabetes and chronic kidney disease.
“Whereas mineralocorticoid receptor antagonists are beneficial in reducing cardiovascular complications, direct mechanistic pathways for these effects in humans are lacking,” says principal investigator Sanjay Rajagopalan, MD, Chief of Cardiovascular Medicine for University Hospitals Harrington Heart & Vascular Institute and the Herman K. Hellerstein, MD, Professor of Cardiovascular Research.
University Hospitals Harrington Heart & Vascular Institute served as trial coordinating center for the four MAGMA sites, serving as a data coordinating center, magnetic resonance imaging (MRI) core lab and drug distribution center.
The randomized, double-blind, placebo-controlled MAGMA trial tested a dose of 25 mg of spironolactone versus in placebo in patients with high-risk type 2 diabetes with Stage 3-4 chronic kidney disease (not receiving dialysis) on maximum tolerated renin-angiotensin system blockade which meant that these patients were already on angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Spironolactone was well tolerated in the MAGMA trial, with an incidence of hyperkalemia of 8% if used appropriately per protocol guidance. The primary endpoint was thoracic aortic wall volume while the secondary endpoints were left ventricular mass and fibrosis measured using changes in T1 relaxivity of the left ventricular (LV) myocardium. Tertiary endpoints included 24-hour ambulatory pressures, central blood pressure and plasma proteomic analysis.
“The outcomes of the trial showed that spironolactone effectively halted aortic wall volume or atherosclerosis progression and induced regression in LV mass and fibrosis,” Dr. Rajagopalan and MAGMA colleagues write in the journal Circulation. Plasma proteomic analysis involving >7000 proteins revealed changes in several proteins that reflected anti-inflammatory and antifibrotic mechanisms that may have provided benefit. Mediation analysis strongly suggested that the effects of spironolactone were independent of blood pressure. These data suggest a role for generic Spironolactone in patients with high-risk type 2 diabetes and chronic kidney disease, where other more expensive options are not feasible.