JACC in a Flash: NT-proBNP: Guiding Primary Prevention of CVD in Diabetic Patients

Oct 16, 2013

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Diabetes is one of the main factors leading to development of cardiac disease, yet little research has focused on finding preventive therapies in this population. The biomarker N-terminal pro-B natriuretic peptide (NT-proBNP) is recognized as one of the best predictors for both short- and intermediate-term cardiovascular events—so could elevated levels of NT-proBNP help identify diabetic patients at the greatest risk for cardiac disease?

In the PONTIAC (NT-proBNP Selected Prevention of Cardiac Events in a Population of Diabetic Patients Without a History of Cardiac Disease) trial, Martin Huelsmann, MD, and colleagues hypothesized that the uptitration of neurohumoral therapies (renin-angiotensin system [RAS]-antagonists, ACE-Is or ARBs, and beta-blockers) would be most effective for the prevention of cardiac events in a subgroup of diabetic patients who had elevated NT-proBNP concentrations at baseline. A total of 268 diabetic patients completed the study: 131 patients who were randomized to the “control” treatment group and 137 patients in the “intensified” treatment group.

Table: Risk Reductions of Endpoints with Intensified Treatment
Endpoint Hazard Ratio
Primary endpoint 0.351 (p = 0.04; 95% CI 0.127-0.975)
All-cause hospitalizations 0.657 (p = 0.02; 95% CI 0.465-0.927)
Unplanned cardiovascular hospitalizations or death 0.376 (p = 0.03; 95% CI 0.157-0.899)
Heart failure hospitalizations 0.140 (p = 0.07; 95% CI 0.017-1.137)
Control treatment consisted of visits to a diabetes care unit at baseline, 3, 6, and 12 months, where patients were given guideline-based treatments if appropriate; “intensified” treatment consisted of additional treatment at a cardiac outpatient clinic for the individualized uptitration of RAS-antagonists and beta-blockers.

Using NT-proBNP concentration appeared to identify diabetic patients who would benefit from neurohumoral therapy: after 2 years, randomization to the biomarker-guided “intensified” group was associated with a 65% reduction in risk of the primary endpoint (hospitalization or death due to cardiac disease; TABLE). There were no major side effects requiring hospitalization, suggesting that targeted blocking of neurohumoral activation with aggressive uptitration was effective and safe, even in an already well-treated population. However, contrary to Dr. Huelsmann and colleagues’ hypothesis, allocation to a treatment group did not result in a significant decrease in NT-proBNP levels.

“It is well known from clinical practice that the cardiovascular risk of individual diabetes patients varies widely,” the authors wrote, noting that future study in larger populations is required to validate the findings of the present study—particularly in patients with low NT-proBNP to determine if treatment effect is exclusively present in patients with higher biomarker concentrations. “We would expect that based on the low event rates in a population with low NT-proBNP the number to treat would be substantially higher than in the population presented in the PONTIAC trial.”

Huelsmann M, Neuhold S, Resl M, et al. J Am Coll Cardiol. 2013;62:1365-72.

Keywords: Biomarkers, Cardiovascular Diseases, Renin-Angiotensin System, Risk Factors, Diabetes Mellitus, Primary Prevention, Natriuretic Peptide, Brain


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