A Biomarker-Based Score for Risk of Hospitalization for Heart Failure in Patients With Diabetes
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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<b>Objective:</b> 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.
<p><b> </b></p>
<p><b>Research
Design and Methods:</b> 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.</p>
<p> </p>
<p><b>Results:</b> 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).</p>
<p> </p>
<p><b>Conclusions:</b> 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.</p>
<br>
<p> </p>
Funding
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).
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