Assessing for a Differential Treatment Effect with Nesiritide by Body Mass Index

Abstract

Introduction Visceral fat is associated with increased clearance of natriuretic peptides. As such, a brain natriuretic peptide (BNP) deficiency has been observed in obese patients, both healthy individuals and those with cardiovascular disease. This study investigated if obese patients with heart failure (HF) exhibited a differential response to nesiritide, a BNP analogue, compared with non-obese patients with regards to reduction of symptoms and clinical outcomes in the ASCEND-HF (Acute Study of Clinical Effectiveness if Nesiritide and Decompensated Heart Failure) trial. Hypothesis Due to enhanced BNP clearance, obese patients with acutely decompensated HF will exhibit a reduced response to nesiritide with regards to dyspnea relief and clinical outcomes. Methods We described baseline congestion phenotype and dyspnea at 6 and 24 hours (not moderately or markedly better) by body mass index (BMI) category ( 35 kg/m2). We assessed for an interaction between BMI (as a categorical variable and continuous measure) and treatment (nesiritide vs. placebo) for the endpoints of 6-hour and 24-hour dyspnea and 30-day rehospitalization or all-cause mortality. We used random-intercept multilevel logistic regression models including pre-specified adjustment covariates, treatment and the BMI x treatment interaction. Results Of the 7,141 patients with HF (including both reduced and preserved ejection fraction), we examined 7077 patients (99%) with baseline BMI data. Among the 7,077 patients, 4,506 (63.7%) had BMI 35 kg/m2. Baseline NT-proBNP levels were lower among patients with higher BMI (median of 5,261 vs. 3633 vs. 2,663 pg/mL, respectively, p 35 had less baseline pulmonary congestion and more peripheral edema. Patients with BMI >35 had more persistent dyspnea at 6 and 24 hours compared to patients with BMI 0.4) (Table). Conclusions Compared with non-obese patients, obese patients with acute HF had lower BNP levels and a different phenotype of congestion as well as more persistent dyspnea at 6 and 24 hours. There was no evidence of a differential treatment effect with nesiritide based on obesity status.