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