Relationship between baseline cardiac biomarkers and cardiovascular death or hospitalization for heart failure with and without sodium–glucose co-transporter 2 inhibitor therapy in DECLARE-TIMI 58

Thomas A. Zelniker, David A. Morrow, Ofri Mosenzon, Erica L. Goodrich, Petr Jarolim, Sabina A. Murphy, Deepak L. Bhatt, Lawrence A. Leiter, Darren K. McGuire, John Wilding, Christoph Bode, Basil S. Lewis, Ingrid Gause-Nilsson, Anna Maria Langkilde, Martin Fredriksson, Itamar Raz, Marc S. Sabatine, Stephen D. Wiviott

Research output: Contribution to journalArticlepeer-review

Abstract

Aims: Dapagliflozin reduced the risk of the composite of cardiovascular (CV) death or hospitalization for heart failure (HHF) in patients with type 2 diabetes mellitus in DECLARE-TIMI 58. We hypothesized that baseline N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT) levels would help identify patients who are at higher baseline risk and we describe the treatment effects of dapagliflozin in patients according to their baseline NT-proBNP and hsTnT levels. Methods and results: This was a pre-specified biomarker study from DECLARE-TIMI 58, a randomized, double-blind, placebo-controlled CV outcomes trial of dapagliflozin. Baseline NT-proBNP and hsTnT levels were measured in the TIMI Clinical Trials Laboratory in 14 565 patients. Among the included patients, 9143 patients (62.8%) were male, 1464 (10.1%) had a history of heart failure and the mean age was 63.9 years. The median baseline NT-proBNP and hsTnT levels were 75 pg/mL [interquartile range (IQR) 35–165] and 10.2 pg/mL (IQR 6.9–15.5), respectively. Patients with higher NT-proBNP and hsTnT quartiles had higher rates of CV death/HHF (Q4 vs. Q1: NT-proBNP: 4-year Kaplan–Meier event rates 13.7% vs. 1.0%; hsTnT: 11.8% vs. 1.4%; P-trend <0.001). Dapagliflozin consistently reduced the relative risk of CV death/HHF regardless of baseline NT-proBNP (P-interaction 0.72) or hsTnT quartiles (P-interaction 0.93). Given their higher baseline risk, patients with NT-proBNP and/or hsTnT levels above the median derived larger absolute risk reductions with dapagliflozin (NT-proBNP 1.9% vs. 0%, P-interaction 0.010; hsTnT 1.8% vs. 0.1%, P-interaction 0.026). Conclusion: Patients with type 2 diabetes mellitus and higher NT-proBNP or hsTnT levels are at increased risk of CV death and HHF. Dapagliflozin reduced the relative risk of CV death/HHF irrespective of NT-proBNP and hsTnT levels, with greater absolute risk reductions seen in patients with higher baseline biomarker levels.

Original languageEnglish (US)
JournalEuropean Journal of Heart Failure
DOIs
StateAccepted/In press - 2020

Keywords

  • Biomarker
  • Dapagliflozin
  • High-sensitivity troponin T
  • NT-proBNP
  • Sodium–glucose co-transporter 2 inhibitors
  • Type 2 diabetes mellitus

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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