Science and Research

Identifying potential parameters associated with response to switching from a PDE5i to riociguat in RESPITE

BACKGROUND: RESPITE evaluated patients with pulmonary arterial hypertension and an inadequate response to phosphodiesterase type 5 inhibitors (PDE5i) who switched to riociguat. This post hoc analysis assessed response to this switch in parameters associated with clinical improvement. METHODS: RESPITE was a 24-week, uncontrolled pilot study (n = 61). Differences in functional, hemodynamic, and cardiac function parameters, REVEAL risk score (RRS), and biomarkers were compared between responders (free from clinical worsening, World Health Organization functional class I/II, and >/=30 m improvement in 6-min walking distance at Week 24) and non-responders. RESULTS: Of 51 patients (84%) completing RESPITE, 16 (31%) met the responder endpoint. At baseline, there were significant differences between responders and non-responders in N-terminal prohormone of brain natriuretic peptide (NT-proBNP), growth/differentiation factor 15 (GDF-15), and RRS, whereas there were no differences in hemodynamics or cardiac function. At Week 24, responders had significant improvements in pulmonary arterial compliance, pulmonary vascular resistance, and mean pulmonary arterial pressure, while non-responders showed no significant change. Cardiac efficiency and stroke volume index significantly improved irrespective of responder status. CONCLUSIONS: NT-proBNP, GDF-15, and RRS were identified as potential predictors of response in patients switching from PDE5i to riociguat. Further prospective controlled studies are needed to confirm the association of these parameters with response.

  • Benza, R. L.
  • Corris, P. A.
  • Klinger, J. R.
  • Langleben, D.
  • Naeije, R.
  • Simonneau, G.
  • Ghofrani, H. A.
  • Jansa, P.
  • Rosenkranz, S.
  • Scelsi, L.
  • Thenappan, T.
  • Raina, A.
  • Meier, C.
  • Busse, D.
  • Hoeper, M. M.

Keywords

  • Biomarkers
  • Pulmonary arterial hypertension
  • Pulmonary hemodynamics
  • Right heart function
  • Riociguat
  • Switching to riociguat
  • Actelion, and EIGER. PAC reports grants and personal fees (University Research
  • Fund) from Bayer AG, and personal fees from Actelion and GSK. JRK reports his
  • institution received grant support for clinical trials in pulmonary hypertension
  • from Actelion, Bayer AG, Lung Biotechnology, and United Therapeutics. DL reports
  • honoraria, consultation fees, research support, and/or travel expenses from
  • Actelion, Arena, Bayer AG, Northern Therapeutic, PhaseBio, and United
  • Therapeutics. RN reports Advisory Board member fees from Actelion, Bayer AG, and
  • Lung Biotechnology Corporation, personal fees from Actelion and GSK, and grants
  • from Reata. GS reports grants, personal fees, and non-financial support from
  • Actelion, Bayer AG, GSK, and Merck. HAG reports grants and personal fees from
  • Actelion, Bayer AG, Ergonex, and Pfizer, and personal fees from Gilead, GSK,
  • Merck, and Novartis. PJ reports being an investigator for Actelion and Bayer AG,
  • and personal fees from AOP. SR reports grants and personal fees from Actelion,
  • Bayer AG, Gilead, GSK, Novartis, Pfizer, United Therapeutics, Arena, Ferrer,
  • Merck Sharp&Dohme, and Abbott, and research support from Actelion, Bayer AG,
  • Novartis, Pfizer, and United Therapeutics. LS has nothing to disclose. TT reports
  • personal fees (Advisory Board/CME) from Actelion and Gilead. AR reports honoraria
  • from Bayer AG, research support from United Therapeutics, and consulting fees
  • from St Jude. CM is an employee of Bayer AG. DB was an employee of Chrestos
  • Concept GmBH & Co during writing of the manuscript. MMH reports consultancy fees
  • from Actelion, Bayer AG, and Pfizer, and personal fees from Actelion, Bayer AG,
  • Pfizer, and MSD.
Publication details
DOI: 10.1016/j.ijcard.2020.05.044
Journal: Int J Cardiol
Pages: 188-192 
Work Type: Original
Location: BREATH, UGMLC
Disease Area: PH
Partner / Member: JLU, MHH
Access-Number: 32461118
See publication on PubMed

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