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.