Renal and Cardiovascular Outcomes of SGLT2 Inhibitors versus ARNI in Cardiorenal Syndrome: A Network Meta-Analysis of Randomized Controlled Trials

Gladian Yanuriska (Department of Internal Medicine, Faculty of Medicine, Universitas Andalas, Padang, Indonesia)
Taufik Rizkian Asir (Department of Internal Medicine, Division of Cardiovascular, Faculty of Medicine, Universitas Andalas, Padang, Indonesia)
Wahyudi (Department of Internal Medicine, Division of Cardiovascular, Faculty of Medicine, Universitas Andalas, Padang, Indonesia)

Bioscientia Medicina : Journal of Biomedicine and Translational Research
Vol. 10 No. 5 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research

Background: Cardiorenal syndrome involves complex pathophysiological cross-talk between the heart and kidneys, frequently culminating in refractory pulmonary congestion. Two primary pharmacological pillars, Sodium-Glucose Cotransporter-2 inhibitors and Angiotensin Receptor-Neprilysin Inhibitors, independently provide profound cardiovascular and renal benefits. However, direct comparative efficacy remains unquantified, creating clinical dilemmas in therapeutic sequencing. Methods: A systematic review and network meta-analysis were conducted utilizing nine pivotal randomized controlled trials. A frequentist network meta-analysis approach utilizing random-effects models was employed. Time-to-event and continuous outcomes were harmonized and pooled utilizing Standardized Mean Differences to allow for indirect head-to-head comparisons between the two drug classes. Results: The network comprised 43,450 patients. Both therapies significantly reduced cardiovascular events compared to standard care. In indirect comparisons, Angiotensin Receptor-Neprilysin Inhibitors demonstrated a superior reduction in the risk of urgent heart failure hospitalizations (Standardized Mean Difference -0.14; 95 percent Confidence Interval, -0.27 to -0.01) compared to Sodium-Glucose Cotransporter-2 inhibitors. Conversely, regarding the primary composite renal outcome (estimated glomerular filtration rate decline, end-stage renal disease, or renal death), Sodium-Glucose Cotransporter-2 inhibitors exhibited overwhelming statistical superiority over Angiotensin Receptor-Neprilysin Inhibitors (Indirect Standardized Mean Difference -0.35; 95 percent Confidence Interval, -0.50 to -0.20; p<0.001). Conclusion: Both drug classes are indispensable for managing cardiorenal syndrome. Angiotensin Receptor-Neprilysin Inhibitors provide superior acute cardiovascular hemodynamic relief, whereas Sodium-Glucose Cotransporter-2 inhibitors offer unparalleled long-term structural protection of renal function. Tailored therapeutic sequencing must leverage these distinct physiological advantages.