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.

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Pulmonary Arterial Hypertension


Gérald Simonneau, Hossein-Ardeschir Ghofrani, Paul A. Corris, Stephan Rosenkranz, Ekkehard Grünig, Jim White, Vallerie V. McLaughlin, David Langleben, Christian Meier, Dennis Busse, Frank Kleinjung, Raymond L. Benza

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Pulmonary Circulation Vol 10: No 4 cover image

October 2020

Pulmonary Circulation Vol 10: No 4

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