Abstract
BACKGROUND: The 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America heart failure (HF) classification incorporates cardiac biomarkers to identify early risk of HF. The HF stages may also guide the prognosis and management of cardiovascular and kidney-related events. METHODS: SCORED (Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients With Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk) was a randomized trial in diabetes with kidney disease comparing sotagliflozin versus placebo on cardiovascular death, HF hospitalizations, and urgent HF visits. SCORED participants were grouped by HF stage post hoc. Stage A: no HF, normal biomarkers (NT-proBNP [N-terminal pro-B-type natriuretic peptide] <125 pg/mL; high sensitivity cardiac troponin T [hs-cTnT] <14 ng/L), and normal cardiac structure/function. Stage B (pre-HF): no HF but elevated NT-proBNP, hs-cTnT, or abnormal cardiac structure/function. Stage C/D: symptomatic HF. End points include the primary composite (cardiovascular death and HF-related events), major adverse cardiovascular events, and kidney-related composites (≥50% decline in estimated glomerular filtration rate, kidney failure, or kidney death). Using competing-risk proportional hazards models, we examined the association between HF stage and these end points, and the effect of sotagliflozin versus placebo by HF stage. RESULTS: There were 741 patients (7%) in stage A, 6560 (62%) in stage B (pre-HF), and 3283 (31%) in stage C/D (established HF). The median NT-proBNP and hs-cTnT increased with HF stage. Increasing HF stage was associated with a 2- to 4-fold increase in the primary outcome/major adverse cardiovascular events in the placebo group. The kidney-specific composite was 5-fold higher in stage B (pre-HF) versus stage A but similar in stages B and C/D. The effect of sotagliflozin versus placebo was similar, irrespective of HF stage (primary outcome: hazard ratio, 0.74 [95% CI, 0.63-0.88]; P(interaction)=1.00), with higher absolute benefit in each HF stage (P-trend(IRR)=0.002). The absolute benefit for the kidney-specific end point was comparable for stages B and C/D. CONCLUSIONS: Increasing HF stage is associated with a higher risk of HF, major adverse cardiovascular events, and kidney events. Asymptomatic stage B (pre-HF) increased cardiovascular and renal events by >2- and 5-fold, respectively. The benefits of sotagliflozin are consistent, irrespective of HF stage.