Comparative efficacy and safety of different SGLT2 inhibitor-based combination strategies in HFrEF: a systematic review and network meta-analysis
Abstract
Background: The optimal combination therapy for heart failure with reduced ejection fraction (HFrEF) involving sodium-glucose transporter 2 inhibitors (SGLT2i), angiotensin receptor-neprilysin inhibitors (ARNI), and conventional triple therapy remains uncertain due to the lack of direct comparative evidence.
Methods: We conducted a Bayesian network meta-analysis of randomized controlled trials (RCTs) comparing six treatment regimens. Primary outcome was the composite of cardiovascular death and hospitalization. Secondary outcomes included all-cause mortality, Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, 6-minute walk distance (6MWD), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and adverse events (hypotension, hyperkalemia, renal events). All analyses were performed under a Bayesian statistical framework, and the relative efficacy and safety of the six regimens were ranked using surface under the cumulative ranking curve (SUCRA) probabilities.
Results: A total of 22 studies (21 RCTs) involving 24,499 patients were included. For the primary composite outcome, Sotagliflozin-based quadruple therapy ranked first (SUCRA: 90.8%; OR: 0.49, 95%CI: 0.16 to 1.47). Dapagliflozin+triple therapy (SUCRA: 76.8%; OR: 0.83, 95%CI: 0.69 to 0.98) and ARNI+BB+MRA (SUCRA: 76.6%; OR: 0.83, 95%CI: 0.75 to 0.92) demonstrated significant reductions in all-cause mortality. ARNI-based triple therapy was associated with a significantly increased risk of hypotension (OR:…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 24,499 participants or records.
Read the paper
Related studies
- Strategy for Mitigating DKA Risk in Patients with Type 1 Diabetes on Adjunctive Treatment with SGLT Inhibitors: A STICH Protocol
- Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance
- SGLT2 Inhibitors in Heart Failure: Targeted Metabolomics and Energetic Metabolism
- Mechanisms of blood pressure reduction with sodium-glucose co-transporter 2 (SGLT2) inhibitors
- Sodium-glucose cotransporter inhibitors: beyond glycaemic control
- Decoding the effects of SGLT2 inhibitors on cardiac arrhythmias in heart failure
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.