Serial assessment of NT-proBNP and high-sensitivity cardiac troponin with glucagon-like peptide-1 receptor agonist therapy in type 2 diabetes: Insights from EXSCEL.
Baseline NT-proBNP and cTnI are strong prognostic markers for adverse cardiovascular outcomes in type 2 diabetes patients, with significant increases over one year indicating higher risk.
Where it sits
this study against the rest of the dulaglutide corpusSummary and findings
This study evaluated the prognostic value of NT-proBNP and high-sensitivity cardiac troponin I in patients with type 2 diabetes undergoing exenatide therapy. A total of 4,292 participants had biomarker assessments at baseline and 1 year. The study found that baseline NT-proBNP and cTnI were strong prognostic markers for major adverse cardiovascular events and mortality.
Abstract
<h4>Background</h4>In the EXSCEL trial, exenatide did not reduce major adverse cardiovascular events (MACE), but heterogeneity of benefit and the role of cardiac biomarkers remain uncertain. We evaluated the prognostic value of baseline and 1-year changes in N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (cTnI), and whether baseline biomarker concentrations modified exenatide effects.<h4>Methods</h4>EXSCEL randomized 14,752 adults with type 2 diabetes to exenatide 2 mg weekly (EQW) or placebo. In a biomarker cohort, 4,292 participants had serial NT-proBNP or cTnI at baseline and 1 year. Biomarkers were log transformed and Cox models related baseline concentrations and 1-year change to MACE, all-cause mortality (ACM), cardiovascular (CV) death, hospitalization for heart failure (hHF), adjusting for clinical covariates and the alternate biomarker. Treatment interaction was tested with biomarker by treatment terms.<h4>Results</h4>Over median 1,480 days follow-up, 529 MACE, 310 all cause deaths, 193 CV deaths, and 157 hHF events occurred. Baseline NT-proBNP was strongly prognostic (adjusted HR per 1 integer unit 1.63 for MACE, 1.85 for ACM, 2.17 for CV death, and 2.17 for hHF; all P < .001). Baseline cTnI was also prognostic with a nonlinear pattern, with risk rising mainly above the median. Per SD rise in NT-proBNP over 1 year predicted later MACE (HR 1.85) and CV death (HR 2.81; both P < .001). Baseline NT-proBNP didn't modify treatment effects. Baseline cTnI didn't modify EQW treatment effect on MACE but lower rates of CV deaths and hHF with EQW were observed at higher cTnI concentrations.<h4>Conclusions</h4>NT-proBNP and cTnI were strong prognostic markers of adverse outcomes in patients with type 2 diabetes and their 1-year increases signaled higher subsequent risk. Baseline cTnI may mark heterogeneity of EQW response, but mortality interactions are hypothesis generating and require confirmation.
Background
This paper addresses the prognostic implications of cardiac biomarkers NT-proBNP and high-sensitivity cardiac troponin I in patients with type 2 diabetes treated with exenatide. Prior studies indicated that exenatide did not reduce major adverse cardiovascular events, but the role of biomarkers in assessing cardiovascular risk remained unclear. Understanding these relationships is crucial for improving risk stratification in this population.
Methods
The study utilized data from the EXSCEL trial, which randomized 14,752 adults with type 2 diabetes to receive exenatide 2 mg weekly or placebo. In a biomarker cohort, 4,292 participants had serial measurements of NT-proBNP and cTnI at baseline and after 1 year. The primary outcomes included major adverse cardiovascular events, all-cause mortality, cardiovascular death, and hospitalization for heart failure, analyzed using Cox models adjusting for clinical covariates.
Results
Over a median follow-up of 1,480 days, there were 529 major adverse cardiovascular events. Baseline NT-proBNP was found to be a strong prognostic marker for MACE with an adjusted hazard ratio of 1.63 per 1 integer unit increase (P < .001). Additionally, a per standard deviation increase in NT-proBNP over 1 year predicted MACE with a hazard ratio of 1.85 (P < .001).
Interpretation
The findings align with existing literature that identifies NT-proBNP and cTnI as significant prognostic markers in cardiovascular risk assessment. However, while the statistical significance is clear, the clinical significance of these findings may vary, particularly given the observed effect sizes. The study's observational nature and potential confounding factors limit the ability to draw definitive conclusions about treatment efficacy.
Key findings
- 529 MACE events occurred over median 1,480 days follow-up, n=14,752.
- Adjusted HR per 1 integer unit of baseline NT-proBNP for MACE was 1.63, P < .001.
- Per SD rise in NT-proBNP over 1 year predicted MACE with HR 1.85, P < .001.
- Baseline NT-proBNP was prognostic for all-cause mortality with HR 1.85, P < .001.
- Baseline cTnI was prognostic for cardiovascular death with HR 2.17, P < .001.
Limitations
- Observational nature of biomarker assessments.
- Potential confounding factors not fully controlled.
- Findings based on a single trial cohort.
- No direct treatment efficacy claims made.