Right ventricular (RV) failure is the primary cause of death in pulmonary artery hypertension (PAH). Despite being the gold standard investigation for RV failure, cardiac MRI (CMR) is not routinely used in PAH patients.
In the recently published REPAIR study, Noordegraaf et al have provided robust evidence to support the potential use of CMR to assess RV cardiac function in future clinical trials in PAH. In addition to improving hemodynamic parameters (PVR, mPAP, cardiac index), PAH treatment with dual endothelin receptor antagonist macitentan as monotherapy or part of combination therapy resulted in improved RV function and structure. The study was recently published in JACC Cardiovascular Imaging.
Macitentan, approved for the long-term treatment of PAH, is recommended for use as monotherapy or combination therapy. The REPAIR (Right vEntricular remodeling in Pulmonary ArterIal hypeRtension) study aimed to evaluate the effect of macitentan on RV and hemodynamic outcomes in patients with symptomatic PAH, using CMR and right heart catheterization (RHC).
In this prospective, multicenter, single-arm, open-label, 52-week, phase 4 study, the effect of macitentan 10 mg, with or without phosphodiesterase type-5 inhibition, on RV remodeling and function and cardiopulmonary hemodynamics were studied.
Primary endpoints were change from baseline to week 26 in RV stroke volume, determined by CMR; and pulmonary vascular resistance, determined by RHC. Efficacy measures were assessed for all patients with baseline and week 26 data for both primary endpoints.
Macitentan treatment, alone or in combination with a PDE-5i, led to statistically significant and clinically relevant improvements in RV stroke volume (RVSV) and pulmonary vascular resistance (PVR) at week 26, with improvements in RVSV maintained at week 52. RV stroke volume increased by 12 mL and pulmonary vascular resistance decreased by 38%at week 26.
Improvements were also seen in the majority of the secondary and exploratory CMR (RV and LV variables and the RV/LV volumetric ratios), hemodynamic, and functional endpoints.
That beneficial changes were observed for both RV function (RVSV and RVEF) and structure (RVESV and RV mass) suggests that macitentan contributes to beneficial remodeling of the RV in patients with PAH.
This drug also improved hemodynamic parameters with significant reductions in PVR, mPAP and an increase in cardiac index. Patients who received macitentan as initial double combination therapy with a PDE-5i had numerically larger improvements than those initiating macitentan alone (either as monotherapy or sequential combination therapy), supporting the treatment approach recommended in the European Society of Cardiology/European Respiratory Society guidelines.
Improvements were also seen in several key clinical parameters in the REPAIR study; 6MWD significantly increased from baseline to week 26, and the majority of patients had an improvement in WHO functional class.
The most frequent adverse events (≥20% of patients) were peripheral edema (n = 19, 21.8%) and headache (n = 18, 20.7%).
The REPAIR study provides evidence that macitentan treatment significantly improves RV function and structure in patients with PAH. The consistent CMR results reported here, and in other studies, underscore the clinical relevance of this noninvasive imaging technique in monitoring PAH disease status and progression, and provide further confidence in CMR-assessed endpoints and their potential use in future trials.
Source: JACC Cardiovascular Imaging: DOI: 10.1016/j.jcmg.2021.07.027