Comparing the Long-Term Effectiveness of Sodium-Glucose Cotransporter 2 Inhibitors Versus Mineralocorticoid Receptor Antagonists as Add-On Therapies in the Management of Heart Failure: A Systematic Review.

We sought to conduct a systematic review to compare the long-term effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors and mineralocorticoid receptor antagonists (MRAs) when they are added to guideline-mediated therapy to treat patients with heart failure. To undertake this task, we searched PubMed, MEDLINE, Scopus, and ClinicalTrials.gov from 2020 to 2025. Randomized controlled trials (RCTs) were selected if they investigated both of the pre-specified outcomes that measured long-term effectiveness. A total of five trials were included: four trials studying SGLT2 inhibitors and one trial studying MRAs. A total of 14340 heart failure patients were included from both cohorts: 8339 in the SGLT2 inhibitor cohort and 6001 in the MRA cohort. Both SGLT2 inhibitors and MRAs significantly reduced the risk of worsening heart failure events (SGLT2 inhibitors by 25.21% and MRAs by 17.93%) and cardiovascular deaths (SGLT2 inhibitors by 14.36% and MRAs by 7.16%) when compared to placebo. A head-to-head comparison of both drug classes showed that SGLT2 inhibitors fared better than MRAs in reducing worsening heart failure events and cardiovascular deaths.