Aggressive drug therapy prevented CV in diabetics selected using NT-proBNP

Patients with diabetes who have elevated levels of amino-terminal pro–B-type natriuretic peptide may be less likely to develop cardiac events if administered accelerated up-titration of renin-angiotensin system antagonists and beta-blockers, according to results of the PONTIAC study.

Researchers conducted the prospective, randomized, controlled PONTIAC study to assess the primary preventive effect of neurohormonal therapy in high-risk patients with type 2 diabetes selected by amino-terminal pro–B-type natriuretic peptide (NT-proBNP). Previous research has indicated that diabetes patients with NT-proBNP concentrations >125 pg/mL are at high risk for cardiac events. Thus, this study focused only on patients with levels >125 pg/mL (n=300; 63% women).

Patients were divided into two groups: a control group that received antiplatelet therapy, antihyperglycemic therapy and lipid-lowering agents or an intensified group that received the aforementioned therapies plus up-titration of renin-angiotensin system antagonists and/or beta-blockers in maximum tolerated doses.

The primary endpoint was hospitalization or death related to cardiac disease after 2 years. The intensified group experienced fewer hospitalizations or deaths due to cardiac disease vs. the control group (HR=0.351; 95% CI, 0.127-0.975). A similar trend emerged for secondary endpoints, including all-cause hospitalization and unplanned CV hospitalizations/death (P<.05 for all).

Heart rate was reduced in only the intensified group (P=.004); however, BP was significantly reduced in both groups (P<.05).

Median NT-proBNP at baseline was 265.5 pg/mL. After 1 year of intensified treatment, there was no significant decrease in NT-proBNP concentration in either group.

Martin Huelsmann, MD, of the department of internal medicine II, division of cardiology, Medical University Vienna, Austria, and colleagues concluded that accelerated up-titration of therapy is “an effective and safe intervention for the primary prevention of cardiac events for diabetic patients preselected using NT-proBNP.”

G. Michael Felker

In a related commentary, G. Michael Felker, MD, MHS, FACC, and Tariq Ahmad, MD, MPH, both of the division of cardiology, department of medicine, Duke University Medical Center, said using a biomarker to identify candidates for primary disease prevention is an important trend in health care.

“The results of the PONTIAC study suggest that natriuretic peptide-focused therapy may be an important new avenue for targeting at-risk populations for primary prevention strategies,” they wrote. “Studies such as PONTIAC that use a single biomarker to target or modify treatment are likely the tip of an iceberg representing a shift toward a more nuanced view of the diagnoses and treatment of cardiovascular disease.”

Tariq Ahmad

Particularly important in this case, according to Felker and Ahmad, is that “clinically silent processes in the cardiovascular system can gradually shift the homeostatic balance from health to disease far before an index cardiac event. Many of the pathologic processes known to be precursors of cardiovascular disease can lead to increase in natriuretic peptide levels.”

However, “the results of PONTIAC must be replicated before they can be considered to be practice changing,” they added.

For more information:

Felker MG. J Am CollCardiol. 2013;[published online ahead of print June 25].

Huelsmann M. J Am CollCardiol. 2013;[published online ahead of print June 25].

Disclosure: The study was funded by Roche Diagnostics Austria and Roche Rotkreuz Switzerland. The researchers, Ahmad and Felker report no relevant financial disclosures.