American Diabetes Association
TBS-HF(DM) supplement 2021.09.15 (revised)_cx01.pdf (775.09 kB)

A Biomarker-Based Score for Risk of Hospitalization for Heart Failure in Patients With Diabetes

Download (775.09 kB)
posted on 2021-09-17, 18:44 authored by David D. Berg, Stephen D. Wiviott, Benjamin M. Scirica, Thomas A. Zelniker, Erica L. Goodrich, Petr Jarolim, Ofri Mosenzon, Avivit Cahn, Deepak L. Bhatt, Lawrence A. Leiter, Darren K. McGuire, John P.H. Wilding, Per Johanson, Anna Maria Langkilde, Itamar Raz, Eugene Braunwald, Marc S. Sabatine, David A. Morrow
Objective: Heart failure (HF) is an impactful complication of type 2 diabetes mellitus (T2DM). We aimed to develop and validate a risk score for hospitalization for HF (HHF) incorporating biomarkers and clinical factor(s) in patients with T2DM.

Research Design and Methods: We derived a risk score for HHF using clinical data, high-sensitivity troponin T (hsTnT), and N-terminal-pro-B-type natriuretic peptide (NT-proBNP) from 6,106 placebo-treated patients with T2DM in SAVOR-TIMI 53. Candidate variables were assessed using Cox regression. The strongest indicators of HHF risk were included in the score using integer weights. The score was externally validated in 7,251 placebo-treated patients in DECLARE-TIMI 58. The effect of dapagliflozin on HHF was assessed by risk category in DECLARE-TIMI 58.

Results: The strongest indicators of HHF risk were NT-proBNP, prior HF, and hsTnT (each p<0.001). A risk score using these 3 variables identified a gradient of HHF risk (p-trend<0.001) in the derivation and validation cohorts, with c-indices of 0.87 (95%CI, 0.84-0.89) and 0.84 (0.81-0.86), respectively. Whereas there was no significant effect of dapagliflozin vs. placebo on HHF in the low-risk group (hazard ratio [HR] 0.98[0.50-1.92]), dapagliflozin significantly reduced HHF in the intermediate-, high-, and very high-risk groups (HR 0.64[0.43-0.95], 0.63[0.43-0.94], and 0.72[0.54-0.96], respectively). Correspondingly, absolute risk reductions increased across these latter 3 groups: 1.0%(0.0%-1.9%), 3.0%(0.7%-5.3%), and 4.4%(-0.2%-8.9%) (p-trend<0.001).

Conclusions: We developed and validated a risk score for HHF in T2DM that incorporated NT-proBNP, prior HF, and hsTnT. The risk score identifies patients at higher risk of HHF who derive greater absolute benefit from dapagliflozin.


The SAVOR-TIMI 53 and DECLARE-TIMI 58 trials were supported by institutional research grants to Brigham and Women’s Hospital from AstraZeneca. Biomarker testing was supported by grants from Roche Diagnostics (reagent only). D.D.B., S.D.W., B.M.S., M.S.S., and D.A.M., were supported for the present analysis by the American Heart Association Cardiometabolic Health & Type 2 Diabetes Mellitus Strategically Focused Research Network (20SFRN35120087).


Usage metrics

    Diabetes Care


    Ref. manager