Abstract 20293: Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy of B-Type Natriuretic Peptide for the Preservation of Left Ventricular Function Post Anterior Myocardial Infarction
Background: BNP is a hormone with cardio-protective properties which include inhibition of hypertrophy and fibrosis. Previously in a non-placebo controlled, open-label pilot study in human ST elevation anterior acute myocardial infarction (AMI), we reported that a 72 hour intravenous infusion (IV) of BNP (nesiritide) at a dose of 0.006 ug/kg/min suppressed aldosterone, reduced cardiac dilatation and improved LV EF at 1 month compared to baseline.
Methods and Design: This is a proof of concept randomized, double-blind, placebo-controlled, single center clinical trial, to assessed the efficacy of 72 hour IV infusion of BNP (0.006 ug/kg/min) in humans with first time ST-elevation anterior AMI and successful reperfusion, in preventing adverse LV remodeling. A total of 59 patients were randomized to placebo or BNP therapy. The primary efficacy endpoint is LV end-systolic and diastolic volumes determined by MUGA scan between placebo and BNP group at 30 days; secondary endpoints include 30 day LV EF and infarct size measured by MRI. (NCT00573144)
Results: Of the 59 patients randomized, 6 subjects did not complete the 30 day follow up resulting in 53 patients in the final analysis (n=25 BNP and n=28 placebo). Baseline characteristics were similar between the 2 groups. At 30 days, LV volumes and EF were similar between the BNP and placebo groups. However, there was a non-significant trend for infarct size to be smaller in the BNP group versus the placebo group (12±9 vs 17±14 %, p=0.26). In the subgroup of patients with LV EF < 40 % at baseline, there was a non-significant trend for greater reduction LV end systolic volume at 30 days from baseline in the BNP vs placebo group (-16±19 vs -9±65 ml/m2 ,p =0.11). Importantly, there was a strong trend for infarct size to be smaller in the BNP group (16.5±15 vs 28± 14 %,p=0.06).
Conclusion: In this first randomized, double-blind, placebo-controlled proof of concept clinical trial, in humans with ST-elevation anterior AMI, there was a suggestion for BNP to reduce infarct size and a trend for reduced LV volume in those with reduced LV EF. This trial lays the foundation for a larger optimally powered trial to establish if BNP have favorable effects on LV infarct size and remodeling post AMI in patents with reduced LV EF at baseline.
Author Disclosures: H.H. Chen: Research Grant; Significant; Scios Inc, NHLBI. Ownership Interest; Modest; Zumbro Discovery. Consultant/Advisory Board; Modest; Niles Therapeutics and Anexon inc. S.J. Sangaralingham: None. I.P. Clements: None. B.P. Shapiro: None. J. Glockner: None. P.M. McKie: None. J.A. Schirger: None. J.C. Burnett: Research Grant; Significant; NHLBI. Ownership Interest; Modest; Zumbro discovery. Consultant/Advisory Board; Modest; Niles Therapeutics and Anexon inc.
- © 2014 by American Heart Association, Inc.