Science and Research

Assessment of the REPLACE study composite endpoint in riociguat-treated patients in the PATENT study

The goal of treatment in patients with pulmonary arterial hypertension is to achieve a low risk status, indicating a favorable long-term outcome. The REPLACE study investigated the efficacy of switching to riociguat in patients with pulmonary arterial hypertension and an insufficient response to phosphodiesterase-5 inhibitors. In this post hoc analysis, we applied the REPLACE composite endpoint of clinical improvement to the placebo-controlled PATENT-1 study of riociguat in pulmonary arterial hypertension and its long-term extension, PATENT-2. Clinical improvement was defined as ≥2 of the following in patients who completed the study without clinical worsening: ≥10% or ≥30 m improvement in 6-minute walking distance; World Health Organization functional class I or II; ≥30% decrease in N-terminal prohormone of brain natriuretic peptide. At PATENT-1 Week 12, patients treated with riociguat were more likely to achieve the composite endpoint vs. placebo (P < 0.0001), with similar results in pretreated (P = 0.0189) and treatment-naïve (P < 0.0001) patients. Achievement of the composite endpoint at Week 12 was associated with a 45% reduction in relative risk of death and a 19% reduction in relative risk of clinical worsening in PATENT-2. Overall, these data suggest that use of the REPLACE composite endpoint in patients with pulmonary arterial hypertension is a valid assessment of response to treatment.
  • Simonneau, G.
  • Ghofrani, H. A.
  • Corris, P. A.
  • Rosenkranz, S.
  • Grünig, E.
  • White, J.
  • McLaughlin, V. V.
  • Langleben, D.
  • Meier, C.
  • Busse, D.
  • Kleinjung, F.
  • Benza, R. L.

Keywords

  • Pulmonary arterial hypertension
  • clinical worsening
  • soluble guanylate cyclase (sGC) stimulator
  • survival
  • conflicts of interest with respect to the research, authorship, and/or publication
  • of this article: GS reports grants, personal fees, and non-financial support from
  • Actelion, Bayer, GSK, and Merck. H-AG reports non-financial support, grants, and
  • personal fees from Actelion
  • grants and personal fees from Bayer, Novartis
  • Corporation, and Pfizer
  • and personal fees from Gilead Sciences, GSK, and Merck. PAC
  • reports grants and personal fees from Actelion and Bayer, and personal fees from
  • MSD. SR reports remunerations for lectures and/or consultancy from Abbott, Actelion,
  • Arena, Bayer, Ferrer, GSK, MSD, Novartis, Pfizer, and United Therapeutics, and
  • research support from Actelion, Bayer, Novartis, Pfizer, and United Therapeutics. EG
  • reports grants and personal fees from Actelion and Bayer/MSD
  • grants from GSK,
  • Novartis, and United Therapeutics, and personal fees from OrPha Swiss GmbH, SCOPE,
  • and Zurich Heart House. JW reports no conflicts of interest. VVM reports grants,
  • personal fees, and non-financial support from Actelion and Bayer
  • grants from Eiger
  • and SoniVie
  • and personal fees from Arena, Caremark, Medtronic, MSD, and United
  • Therapeutics. DL reports grants, personal fees, and non-financial support from
  • Actelion and Bayer, personal fees from Merck and United Therapeutics
  • and grants
  • from Northern Therapeutics. CM and FK are employees of Bayer AG. DB was an employee
  • of Chrestos Concept GmbH & Co., KG, Essen, Germany at the time of the study and
  • manuscript development. RLB reports grants from Actelion, Bayer AG, Eiger, Gilead,
  • and United Therapeutics paid to his institution, and honoraria from Actelion, Bayer
  • AG and Gilead.
Publication details
DOI: 10.1177/2045894020973124
Journal: Pulm Circ
Pages: 2045894020973124 
Number: 4
Work Type: Original
Location: TLRC, UGMLC
Disease Area: PH
Partner / Member: JLU, Thorax
Access-Number: 33354316

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