The use of ARNi and SGLT2i is highly effective in reducing hospitalization and mortality due to heart failure in patients with ejection fractions ≤40% and ≥ 50%, respectively.

To differentiate between the efficacies of different treatment options, such as renin-angiotensin system inhibitors (RASi), angiotensin receptor neprilysin inhibitors (ARNi) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) for various kinds of congestive heart failure.

This network meta-analysis included randomized controlled studies on different cardiovascular (CV) therapies that examined the risk of CV mortality or hospitalization for heart failure (HHF). Risk ratio (RR) and 95% confidence interval (CI) were evaluated to find the possible link between the intervention and the occurrence of events.

Seventeen research studies were picked which comprised of 61,489 patients. The use of ARNI lowered the possibility of combined CV death or HHF than placebo in individuals having heart failure with reduced ejection fraction (HfrEF  ≤40%). In the case of the outcome of CV death or HHF alone, similar trends were witnessed. SGLT2i showed more beneficial outcomes on CV mortality or HHF events than placebo and RASi in individuals having heart failure with preserved ejection fraction (HFpEF≥ 50%). In case of mortality due to CV, all these 3 therapies could not display positive effects in HfpEF.

Although both SGLT2i and ARNI exhibited beneficial effects, however, SGLT2i was found to be superior to ARNI in the case of the occurrence of HHF in HFpEF. No distinctions in the incidents of withdrawal under these drugs were observed in comparison with placebo or each other in either  HfpEF or HFrEF-affected subjects. Also, SGLT2i had fewer renal injury events in HFrEF whereas no renal injury in HfpEF.

Of all the drugs studied, ARNI had the greatest ability to lessen the occurrence of CV mortality or HHF and SGLT2i exerted fewer renal injury events in HFrEF patients. SGLT2i lowered the risk of CV mortality or HHF in patients with HFpEF. Also, no variations in the occurrence of renal injury were found. Both HFrEF and HFpEF had comparable intolerance of these therapies.