Effect of riociguat on pulmonary arterial compliance in the PATENT and CHEST studies

Thenappan Thenappan, Nadine Al-Naamani, Stefano Ghio, Hossein Ardeschir Ghofrani, Paul M. Hassoun, Marc Pritzker, Adam Torbicki, Sylvia Nikkho, Dennis Busse, Ioana R. Preston

Research output: Contribution to journalArticlepeer-review

Abstract

Pulmonary arterial compliance is a measure of the pulsatile afterload of the right ventricle. Lower pulmonary arterial compliance is associated with reduced right ventricular function and worse prognosis in pulmonary hypertension. The effect of pulmonary vasodilators on pulmonary arterial compliance has not been evaluated in detail in pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. In this post hoc analysis of patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension in the PATENT and CHEST studies, we evaluated the change in pulmonary arterial compliance with riociguat versus placebo. Association of pulmonary arterial compliance with clinical outcomes was assessed using Kaplan–Meier and Cox proportional hazards analyses. Compared with placebo, riociguat significantly improved pulmonary arterial compliance in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. Pulmonary arterial compliance at baseline was associated with survival and clinical worsening-free survival in pulmonary arterial hypertension but only with clinical worsening-free survival in chronic thromboembolic pulmonary hypertension. In patients with pulmonary arterial hypertension, pulmonary arterial compliance at follow-up ≥1.6 mL/mmHg was associated with better outcomes than pulmonary arterial compliance <1.6 mL/mmHg. In patients with chronic thromboembolic pulmonary hypertension, pulmonary arterial compliance at follow-up did not predict outcomes. Cox proportional hazards analyses showed no association between change in pulmonary arterial compliance and outcomes in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. In conclusion, riociguat improved pulmonary arterial compliance in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. Pulmonary arterial compliance at baseline or follow-up, rather than change in pulmonary arterial compliance, is of prognostic importance for outcomes.

Original languageEnglish (US)
JournalPulmonary Circulation
Volume10
Issue number4
DOIs
StatePublished - 2020

Bibliographical note

Funding Information:
TT has received personal fees from Actelion Pharmaceuticals Ltd. and Gilead Sciences Inc. NA-N has received grants from Entelligence Young Investigator Program, ATS/PHA Aldrighetti Research Award for Young Investigators, and K23HL141584. SG, PMH, and MP do not have a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose. H-AG has received grants and personal fees from Actelion Pharmaceuticals Ltd., Bayer AG, ErgoNex Pharma GmbH, and Pfizer and personal fees from Gilead Sciences Inc., GSK, Merck, and Novartis. AT has received personal fees (speaker’s honoraria) from Bayer AG, Bristol-Myers Squibb, and Actelion Pharmaceuticals Ltd. and reports nonfinancial support from Pfizer for congress participation. SN is an employee of Bayer AG. DB was an employee of Chrestos Concept GmbH & Co. KG, Essen, Germany during the writing of this manuscript. IRP has received grants and personal fees from Actelion Pharmaceuticals Ltd., Arena Pharmaceuticals, Bayer AG, Gilead Sciences Inc., and United Therapeutics; grants from Liquidia Technologies; and personal fees from Pfizer and Reata Pharmaceuticals.

Funding Information:
The authors wish to thank the patients and investigators who participated in the PATENT and CHEST studies. The PATENT-1, PATENT-2, CHEST-1, and CHEST-2 studies were supported by Bayer AG (Berlin, Germany) and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. (Kenilworth, NJ, USA). Medical writing services provided by Robyn Bradbury, PhD, of Adelphi Communications Ltd (Macclesfield, UK) were funded by Bayer AG (Berlin, Germany) in accordance with Good Publications Practice (GPP3) guidelines.

Publisher Copyright:
© The Author(s) 2020.

Keywords

  • chronic thromboembolic pulmonary hypertension
  • pulmonary arterial hypertension
  • pulmonary hemodynamics
  • pulmonary hypertension
  • riociguat

PubMed: MeSH publication types

  • Journal Article

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