Abstract 17234: Riociguat Improves Pulmonary Arterial Compliance in Patients With Pulmonary Hypertension due to Systolic Left Ventricular Dysfunction: Results From a Post-hoc Analysis of the Phase IIb Double-Blind, Randomized, Placebo-Controlled, Dose-Ranging Hemodynamic LEPHT Study
Introduction: Reduced pulmonary arterial compliance (PAC) in patients with systolic left ventricular (LV) dysfunction (sLVD) is associated with adverse outcome. In the LEPHT study, riociguat, a novel soluble guanylate cyclase stimulator, improved hemodynamic parameters and health-related quality of life (QoL) in patients with pulmonary hypertension (PH) due to sLVD.
Hypothesis: Riociguat improves PAC in patients with PH-sLVD.
Methods: Overall, 201 patients were randomized to double-blind treatment with oral placebo or riociguat (0.5, 1, or 2 mg 3-times daily) for 16 weeks on top of standard HF treatment in 4 parallel arms. In this post-hoc analysis of the LEPHT study, we analyzed PAC at baseline and Week 16 as stroke volume/(systolic pulmonary artery pressure - diastolic pulmonary artery pressure). The correlation between PAC and other hemodynamic, echocardiographic, clinical, and biomarker variables was also assessed.
Results: In the overall study population at baseline, PAC positively correlated with tricuspid annular plane systolic excursion (Pearson correlation coefficient +0.21 [95% CI 0.05 to 0.35]) and right ventricular (RV) fractional area shortening (+0.23 [0.07 to 0.38]), and negatively correlated with NT-proBNP (-0.22 [-0.37 to -0.07]) and pulmonary capillary wedge pressure (PCWP; -0.36 [-0.49 to -0.22]). Riociguat 2 mg (n=54) significantly increased PAC at Week 16 (least-squares mean difference +0.92 mL/mmHg [0.40 to 1.45]; p=0.0006) vs placebo (n=55), without significantly changing systemic arterial compliance (+0.19 mL/mmHg [-0.04 to 0.43]; p=0.10). The improvement in PAC correlated with change in PCWP (Pearson correlation coefficient -0.49 [-0.60 to -0.36]) and QoL, the latter indicated by decreases in the Minnesota Living with HF total (-0.26 [-0.40 to -0.10]) and physical sub-scores (-0.24 [-0.38 to -0.09]).
Conclusions: In conclusion, PAC was associated with parameters of RV and LV failure in patients with PH-sLVD. Long-term treatment with riociguat reduced RV afterload by lowering pulmonary vascular resistance (as indicated in the main study) and increasing PAC. Improvements in PAC correlated with changes in PCWP and QoL. Whether this effect influences outcome will have to be clarified in larger-scale studies.
- © 2013 by American Heart Association, Inc.