Key result
SGLT2 inhibitors reduce HF hospitalization or CV death ~27% in cardiac amyloidosis with heart failure.
Why the study?
Cardiac amyloidosis was excluded from landmark SGLT2i trials, leaving the efficacy of SGLT2i in cardiac amyloidosis-associated HF entirely undefined despite Class I recommendations across the HF spectrum.
Do SGLT2 inhibitors reduce heart failure hospitalization and all-cause mortality in patients with cardiac amyloidosis-associated heart failure?
Meta-Analysis (n=4,218)
Do SGLT2 inhibitors reduce heart failure hospitalization and all-cause mortality in patients with cardiac amyloidosis-associated heart failure?
This first meta-analysis in cardiac amyloidosis-associated heart failure demonstrates that SGLT2 inhibitors significantly reduce HF hospitalization, all-cause mortality, and symptom burden across both ATTR and AL subtypes, though with an increased risk of symptomatic hypotension.
Answers are grounded in this paper and cite their sources.
Supports SGLT2 inhibitor use in cardiac amyloidosis with HF; extends Class I recommendations to this previously excluded population.
BACKGROUND: Cardiac amyloidosis (CA) — transthyretin (ATTR) and light-chain (AL) subtypes — is the fastest-growing cause of HFpEF yet was excluded from every landmark SGLT2 inhibitor trial (EMPEROR-Preserved, DAPA-HF, DELIVER). SGLT2i now hold Class I recommendations across the HF spectrum, but their efficacy in amyloid cardiomyopathy — defined by restrictive physiology, fibril deposition, and autonomic neuropathy — is entirely undefined. This is the first systematic review and meta-analysis of SGLT2i outcomes specifically in CA-associated heart failure. METHODS: Following PRISMA 2020 , we searched MEDLINE, Embase, Cochrane CENTRAL, and ClinicalTrials.gov through March 2025. Eligible studies included RCTs, prospective cohorts, and registries of SGLT2i versus standard-of-care in biopsy- or scintigraphy-confirmed CA (ATTR or AL) with HF. Primary outcomes: HF hospitalization and all-cause mortality. Secondary outcomes included KCCQ score, NT-proBNP, 6-minute walk distance, eGFR trajectory, and adverse events. Quality assessed by Cochrane RoB 2.0 and Newcastle-Ottawa Scale. Pooled hazard ratios (HR) and standardized mean differences (SMD) used random-effects models. RESULTS: Nineteen studies (n=4,218; ATTR-CA 71%, AL-CA 29%; 4 RCTs, 15 cohorts/registries) were included. SGLT2i significantly reduced HF hospitalization or CV death (HR 0.73, 95% CI 0.63-0.85; p<0.0001; I 2 =27%) and all-cause mortality (HR 0.76, 95% CI 0.64-0.91; p=0.003). KCCQ improved significantly (SMD +6.8 points; p<0.0001); NT-proBNP declined 23% versus control (p=0.0002). Benefit was consistent across ATTR and AL subtypes (p-interaction=0.41). Symptomatic hypotension was higher with SGLT2i (RR 1.48, 95% CI 1.14-1.92; p=0.003). CONCLUSIONS: SGLT2i confer significant, consistent reductions in HF hospitalization, mortality, and symptomatic burden in CA — a population excluded from all foundational trials. Symptomatic hypotension warrants volume-aware titration given restrictive hemodynamics. Current ACC/AHA HF guidelines do not stratify SGLT2i recommendations by etiology; these first pooled data provide compelling evidence to explicitly include CA. A dedicated phase III RCT in cardiac amyloidosis is now both scientifically justified and urgently needed.
No takes yet. Share an insight, caveat, or question.
Krishnan et al. (2026) conducted a meta-analysis in Cardiac amyloidosis-associated heart failure (ATTR or AL subtypes) (n=4,218). SGLT2 inhibitors vs. Standard-of-care / control was evaluated on Heart failure hospitalization or cardiovascular death, and all-cause mortality (HR 0.73, 95% CI 0.63-0.85, p=<0.0001). SGLT2 inhibitors reduced HF hospitalization or CV death (HR 0.73, 95% CI 0.63-0.85; p<0.0001) and all-cause mortality (HR 0.76, 95% CI 0.64-0.91; p=0.003) in cardiac amyloidosis with HF.
Synapse has enriched 10 related papers. Consider them for comparative context: