Abstract
BACKGROUND: Worsening heart failure (WHF) challenges health care with frequent rehospitalizations and reduced quality of life for patients. Despite therapeutic advances, high rehospitalization risks highlight the urgent need for new treatments. OBJECTIVES: This study evaluated the effectiveness of initiating novel therapies during hospitalization or vulnerable phase for WHF patients to reduce rehospitalization risks and determine the optimal treatment sequence. METHODS: A systematic review and network meta-analysis were performed in accordance with Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We included randomized clinical trials from January 2013, to December 2022, sourced from PUBMED and EMBASE, comparing novel heart failure therapies against control. The primary outcome was heart failure rehospitalization. RESULTS: Analysis of 9 randomized clinical trials involving 18,540 patients showed significant rehospitalization reductions with novel treatments, especially sodium-glucose co-transporter 2 inhibitors, angiotensin-neprilysin receptor inhibitor (ARNI), and ferric carboxymaltose. Sotagliflozin led to more pronounced reductions in heart failure hospitalization (OR: 0.50; 95% CI: 0.39-0.63; P < 0.0001), followed by ARNI (OR: 0.54; 95% CI: 0.35-0.83; P = 0.005), ferric carboxymaltose (OR: 0.55; 95% CI: 0.44-0.70; P < 0.0001), empagliflozin (OR: 0.56; 95% CI: 0.39-0.78; P = 0.0007), vericiguat 10 mg (OR: 0.83; 95% CI: 0.74-0.92; P = 0.0008), and finerenone 15 mg (OR: 0.59; 95% CI: 0.38-0.91; P = 0.016). These therapies, when initiated during hospitalization, markedly influenced rehospitalization outcomes. CONCLUSIONS: Early administration of sodium-glucose co-transporter 2 inhibitors, ARNI, and ferric carboxymaltose for WHF patients significantly reduces rehospitalization risk. Our findings support a strategic shift in WHF management, advocating for the rapid introduction of these novel therapies to enhance patient prognosis.