The highest tertile of IGFBP-7 was associated with an increased risk of cardiovascular death or worsening heart failure compared with the lowest tertile (HR 1.48; 95% CI 1.17-1.88).
RCT (n=3,158)
Does elevated IGFBP-7 predict adverse outcomes in patients with HFrEF, and does it modify the benefit of dapagliflozin?
Higher IGFBP-7 levels in HFrEF patients are associated with an increased risk of adverse clinical outcomes, independent of NT-proBNP and hsTnT, and do not modify the clinical benefit of dapagliflozin.
Hazard Ratio: 1.48 (95% CI 1.17–1.88)
BACKGROUND: Insulin-like growth factor-binding protein-7 (IGFBP-7) has been proposed as a potential prognostic biomarker in heart failure (HF), but the association between elevation in IGFBP-7 and HF outcomes in ambulant patients with heart failure with reduced ejection fraction (HFrEF) is unknown. OBJECTIVES: The authors addressed this question in a post hoc analysis of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial. METHODS: The primary outcome was a composite of cardiovascular death or a worsening HF event. The risk of adverse outcome was compared across tertiles of IGFBP-7 concentration by means of Cox proportional hazard models adjusted for N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT). The efficacy of randomized treatment across IGFBP-7 tertiles was assessed. Change in IGFBP-7 at 12 months was compared with the use of geometric means. RESULTS: A total of 3,158 patients had IGFBP-7 measured at baseline, and 2,493 had a repeated measure at 12 months. Patients in the highest tertile of IGFBP-7 had evidence of more advanced HFrEF. The adjusted HR for the primary endpoint in tertile 3, compared with tertile 1, was 1.48 (95% CI: 1.17-1.88). There was no modification of the benefit of dapagliflozin by baseline IGFBP-7 (P interaction = 0.34). Dapagliflozin did not change IGFBP-7 levels over 1 year (P = 0.34). CONCLUSIONS: Higher IGFBP-7 in patients with HFrEF was associated with worse clinical profile and an increased risk of adverse clinical outcomes. IGFBP-7 provided prognostic information incremental to clinical variables, NT-proBNP, and hsTnT. The benefit of dapagliflozin was not modulated by IGFBP-7 level. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure DAPA-HF; NCT03036124).
Adamson et al. (Wed,) conducted a rct in Heart failure with reduced ejection fraction (HFrEF) (n=3,158). Highest tertile of IGFBP-7 vs. Lowest tertile of IGFBP-7 was evaluated on Composite of cardiovascular death or a worsening HF event (HR 1.48, 95% CI 1.17-1.88). The highest tertile of IGFBP-7 was associated with an increased risk of cardiovascular death or worsening heart failure compared with the lowest tertile (HR 1.48; 95% CI 1.17-1.88).
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