A set of biomarkers and clinical variables was found to facilitate the assessment of risk level for expanded heart failure (HF) outcomes in patients with type 2 diabetes mellitus (T2DM) and a recent history of acute coronary syndrome (ACS), according to study results published in the Journal of the American Heart Association.
Although improvements in HF risk stratification post-ACS may help identify patients who would benefit from therapeutic interventions to lower the risk for HF (eg, newer anti-hyperglycemic medications), there have been few studies in which the use of biomarkers and clinical variables was examined in patients with T2D for this purpose.
The study was a sub-analysis of the Examination of Cardiovascular Outcomes with Alogliptin vs Standard of Care (EXAMINE; ClinicalTrials.gov identifier: NCT00968708) trial, a multicenter double-blind non-inferiority placebo-controlled study. In the EXAMINE study, 5380 patients with T2D were randomly assigned to receive alogliptin or placebo after a recent (ie, in the past 15 to 90 days) ACS event. In this cohort, 5154 participants (mean age, 60.9±9.99 years; 67.7% men; 73% white) had baseline biomarker information available; 4291 participants (83.3%) and 1442 participants (28.0%) had a history of hypertension and HF at baseline, respectively.
Biomarkers assayed at baseline included N-terminal pro-B-type natriuretic peptide (NT-proBNP), adiponectin, high-sensitivity troponin I (hs-TnI), galectin-3, and growth-differentiation factor-15 (GDF-15). The study’s primary outcome was an expanded HF composite of cardiovascular mortality, HF hospitalization, loop diuretic initiation, and increase in NT-proBNP levels, which was assessed at a 6-month follow-up visit.
The median follow-up time was 18 months. Patients who did vs did not meet the primary endpoint were older (63.2 vs 60.5 years, respectively), less likely to be men (58.8% vs 69.5%, respectively), and had more cardiovascular comorbidities. The composite outcome was found to be most strongly associated with NT-proBNP level (per log2 hazard ratio [HR], 1.24; 95% CI, 1.18-1.31; P <.0001) and with a history of HF (HR, 1.42; 95% CI, 1.22-1.65; P <.0001) after multivariable adjustment.
An association between the primary outcome and 3 of the 4 other biomarkers was also established: hs-TnI (per log2 HR, 1.04; 95% CI, 1.00-1.09; P =.04), galectin-3 (per log2 HR, 1.21; 95% CI, 1.03-1.41; P =.02), and GDF-15 (per log2 HR, 1.15; 95% CI, 1.04-1.28; P =.007).
The investigators created a statistical model that included the identified biomarkers and clinical variables. This model was found to improve the discrimination of the primary outcome and enable the risk prediction of the expanded HF outcomes (C-statistic = 0.72) compared with the baseline model.
Study limitations include a lack of assessment of additional HF measures.
“Patients with type 2 diabetes mellitus and elevated natriuretic peptide concentrations or prior history of HF face particularly high risks [for] subsequent HF events and warrant closer monitoring,” noted the authors. They recommended that future research continue to explore risk prediction using biomarkers and clinical factors in this population.
Funding and Conflicts of Interest Disclosures:
EXAMINE is a clinical trial sponsored by Takeda Global Research and Development Center, Inc, Deerfield, IL.
Please see original article for conflict of interest declarations.
Sharma A, Vaduganathan M, Ferreira JP, et al. Clinical and biomarker predictors of expanded heart failure outcomes in patients with type 2 diabetes mellitus after a recent acute coronary syndrome: insights from the EXAMINE trial. J Am Heart Assoc. 2020;9(1). doi:10.1161/jaha.119.012797