Comparison of cardiac magnetic resonance imaging, functional and haemodynamic variables in pulmonary arterial hypertension: insights from REPAIR.

Background

Measures that can detect large treatment effects are important for monitoring therapeutic effectiveness. The 2022 European Society of Cardiology/European Respiratory Society guidelines highlight the importance of imaging in monitoring disease status and treatment response in pulmonary arterial hypertension (PAH). Are the standardised treatment effect sizes (STES) of cardiac magnetic resonance imaging (cMRI) comparable with functional and haemodynamic variables?

Methods

REPAIR (ClinicalTrials.gov: NCT02310672) was a prospective, multicentre, single-arm, open-label, 52-week phase 4 study evaluating the effect of macitentan 10 mg, with or without a phosphodiesterase 5 inhibitor (PDE5i), on right ventricular (RV) remodelling, cardiac function and cardiopulmonary haemodynamics. Both cMRI and functional assessments were performed at screening and at weeks 26 and 52; haemodynamic measurements were conducted at screening and week 26. In this

Results

At week 26, large STES (Cohen's d) were observed for 10 of the 20 cMRI variables assessed, including the prognostic measures of RV and left ventricular stroke volume and RV ejection fraction and the haemodynamic trial end-point, pulmonary vascular resistance; medium STES were observed for 6-min walk distance (6MWD). The STES were consistent in treatment-naïve patients and those escalating therapy and maintained at week 52. Similar results were obtained using the non-parametric Cliff's delta method.

Conclusions

The treatment effect of macitentan, alone or in combination with a PDE5i, was comparable for several cMRI and haemodynamic variables with prognostic value in PAH, and greater than that of 6MWD in patients with PAH, highlighting the emerging relevance of cMRI in PAH.

Informations de copyright

Copyright ©The authors 2024.

Déclaration de conflit d'intérêts

Conflict of interests: D.G. Kiely is a steering committee member for Janssen Pharmaceutical Companies of Johnson & Johnson, and receives grant/research support from Janssen Pharmaceutical Companies of Johnson & Johnson, Bayer and GlaxoSmithKline, in addition to other financial or material support, including consultancy and speaker fees, from Janssen Pharmaceutical Companies of Johnson & Johnson, Bayer, GlaxoSmithKline, Ferrer and MSD. Conflict of interests: R. Channick serves as a steering committee member, served on an advisory board, and received research grants/support and speaker fees from Janssen Pharmaceutical Companies of Johnson & Johnson; has served on an advisory board for Bayer; has received consultancy and speaker fees from Bayer and Arena Pharmaceuticals; and has received research grants from United Therapeutics. Conflict of interests: D. Flores is an employee of Janssen Pharmaceutical Companies of Johnson & Johnson. Conflict of interests: N. Galiè is a steering committee member for Janssen Pharmaceutical Companies of Johnson & Johnson; has received grant support, personal fees and non-financial support from Janssen Pharmaceutical Companies of Johnson & Johnson, and has received grant support and personal fees from Bayer Healthcare, Pfizer and GlaxoSmithKline. Conflict of interests: G. MacDonald is an employee of Janssen Pharmaceutical Companies of Johnson & Johnson. Conflict of interests: J.T. Marcus received consultancy fees from Janssen Pharmaceutical Companies of Johnson & Johnson. Conflict of interests: L. Mitchell is an employee of Janssen Pharmaceutical Companies of Johnson & Johnson. Conflict of interests: A. Peacock receives grant/research support from Janssen Pharmaceutical Companies of Johnson & Johnson, Bayer and GlaxoSmithKline, in addition to other financial or material support from Arena Pharmaceuticals Ltd and MSD. Conflict of interests: S. Rosenkranz has served as a steering committee member for Janssen Pharmaceutical Companies of Johnson & Johnson; has received research grants from AstraZeneca, Bayer, Janssen Pharmaceutical Companies of Johnson & Johnson and Novartis; has received speaker and/or consulting fees from and/or been an advisory board member for Abbott, Acceleron, Actelion, Aerovate, Altavant, AOP, Bayer, BMS, Boehringer-Ingelheim, Edwards, Ferrer, Gossamer, Janssen Pharmaceutical Companies of Johnson & Johnson, MSD, Novartis, Pfizer, UT and Vifor. Conflict of interests: A. Tawakol receives consultancy fees from Janssen Pharmaceutical Companies of Johnson & Johnson and Esperion, as well as grant/research support from Genentech. Conflict of interests: A. Torbicki receives consultancy fees from Janssen Pharmaceutical Companies of Johnson & Johnson, Arena Pharmaceuticals Ltd, Bayer, MSD, Pfizer and United Therapeutics, in addition to grant/research support from Janssen Pharmaceutical Companies of Johnson & Johnson, and speaker's bureau fees from Janssen Pharmaceutical Companies of Johnson & Johnson, AOP, Bayer, MSD and Pfizer; they are also an advisory board member for Janssen Pharmaceutical Companies of Johnson & Johnson. Conflict of interests: A. Vonk Noordegraaf receives ongoing grant/research support from Janssen Pharmaceutical Companies of Johnson & Johnson, GlaxoSmithKline and MSD, and speaker's bureau payments from Janssen Pharmaceutical Companies of Johnson & Johnson. Conflict of interests: A.J. Swift has received consultancy fees from Janssen Pharmaceutical Companies of Johnson & Johnson and General Electric Ltd, as well as grant support from GlaxoSmithKline.