Macitentan improves Cardiopulmonary structure and function in PAH patients

A recent study found that Macitentan medication resulted in significant and clinically important improvements in right ventricular (RV) function and structure, as well as cardiopulmonary hemodynamics, in patients with pulmonary arterial hypertension (PAH). Improvements in RV function and structure were maintained after 52 weeks.

This study was conducted by Anton Vonk Noordegraaf and team, results of which were published in the Journal of the American College of Cardiology on 17th November, 2021.

The leading cause of mortality in PAH is RV failure. Cardiac magnetic resonance (CMR) is widely recognized as the most reliable noninvasive approach for monitoring RV function and remodeling, and CMR assessments of RV function and structure are substantially predictive of survival in PAH patients. Regardless, CMR is not commonly employed in PAH clinical studies. Keeping this in mind the objective of this study was to use CMR and right heart catheterization to assess the effect of Macitentan on RV and hemodynamic outcomes in individuals with PAH right heart catheterization (RHC).

REPAIR (Right vEntricular remodeling in Pulmonary Arterial hypertension) was a 52-week, open-label, single-arm, multicenter, phase 4 study that looked at the effects of Macitentan 10 mg with or without phosphodiesterase type-5 inhibition on RV remodeling and function, as well as cardiopulmonary hemodynamics. The primary outcomes were changes in RV stroke volume (as measured by CMR) and pulmonary vascular resistance (as measured by RHC) from baseline to week 26. For all primary objectives, efficacy measures were analyzed for all patients with baseline and week 26 data.

Findings of this study were:

1. Both primary objectives were reached at a predetermined intermediate analysis in 42 patients, enrolment was halted, and the trial was pronounced positive. At week 26, RV stroke volume rose by 12 mL and pulmonary vascular resistance reduced by 38% (n = 71).

2. At week 26, significant improvements were also seen in secondary and exploratory CMR (RV and left ventricular), hemodynamic, and functional goals.

3. At week 52, improvements in CMR RV and left ventricular measures, as well as functional metrics, were sustained. The safety (n = 87) results were consistent with prior clinical studies.

In conclusion, the efficacy of Macitentan was seen to be effective even at the sustained period and it may be used for the treatment. Further studies are needed to provide more rock solid data.

Reference:

Vonk Noordegraaf, A., Channick, R., Cottreel, E., Kiely, D. G., Marcus, J. T., Martin, N., Moiseeva, O., Peacock, A., Swift, A. J., Tawakol, A., Torbicki, A., Rosenkranz, S., & Galiè, N. (2021). The REPAIR Study. In JACC: Cardiovascular Imaging. Elsevier BV. https://doi.org/10.1016/j.jcmg.2021.07.027