Results from the REPLACE (Riociguat rEplacing PDE-5i therapy evaLuated Against Continued PDE-5i thErapy) study in adult patients with pulmonary arterial hypertension (PAH) (WHO Group 1) who were receiving PDE5i therapy and still at intermediate risk1
Randomized, double-blind, multinational, placebo-controlled, 12-
week, phase 3 study2,36MWD = 6-minute walk distance; mPAP = mean pulmonary arterial pressure; PVR = pulmonary vascular resistance; WHO FC = World Health Organization Functional Class.
Improvement in 6MWD was observed at 2 weeks and continued through 12 weeks2
6MWD = 6-minute walk distance.
50% more patients improved WHO FC vs placebo2
ITT = intention-to-treat
Adempas significantly delayed time to clinical worsening2†
†Time to clinical worsening was a combined endpoint defined as death (all-cause mortality), heart/lung transplantation, atrial septostomy, hospitalization due to persistent worsening of pulmonary hypertension, start of new PAH-specific treatment, persistent decrease in 6MWD, and persistent worsening of WHO FC.
‡The Kaplan-Meier plot of time to clinical worsening is presented in the figure above. Patients treated with Adempas experienced a significant delay in time to clinical worsening vs placebo-treated patients (p=0.0046; stratified log-rank test). Significantly fewer events of clinical worsening up to Week 12 (last visit) were observed in patients treated with Adempas (1.2%) compared to placebo (6.3%) (p=0.0285, Mantel-Haenszel estimate).
Right heart catheterization was performed at the beginning and end of the study period in 339 patients.
NT-proBNP = n-terminal prohormone of brain natriuretic peptide; PVR = pulmonary vascular resistance.
‡Placebo-adjusted mean change from baseline.
Results from the REPLACE (Riociguat rEplacing PDE-5i therapy evaLuated Against Continued PDE-5i thErapy) study in adult patients with pulmonary arterial hypertension (PAH) (WHO Group 1) who were receiving PDE5i therapy and still at intermediate risk1
Prospective, randomized, controlled, open-label, international, multicenter study to evaluate the efficacy of Adempas in adult patients with pulmonary arterial hypertension (PAH) (WHO Group 1) who are receiving a stable dose of a PDE5i and still at intermediate risk1
Adult patients with PAH (WHO Group 1) receiving a stable dose of PDE5i with or without concomitant treatment with an ERA for ≥6 weeks and still at intermediate risk1
Composite endpoint of clinical improvement in the absence of clinical worsening at 24 weeks1
Clinical improvement at 24 weeks defined as1:
• Change in 6MWD
• Change in NT-proBNP
• Change in WHO FC
• Time to clinical worsening
6MWD = 6-minute walk distance; ERA = endothelin receptor antagonist; NT-proBNP = n-terminal prohormone of brain natriuretic peptide; PDE5i = phosphodiesterase-5 inhibitor;
WHO FC = World Health Organization Functional Class.
§Clinical improvement at 24 weeks defined as prespecified improvements in 2 out of 3 parameters (6MWD, WHO FC, and/or NT-proBNP) and absence of clinical worsening1†
Clinical Improvement at 24 Weeks1
Change in 6MWD from baseline to 24 weeks1
6MWD = 6-minute walk distance; PDE5i = phosphodiesterase-5 inhibitor.
NT-proBNP = n-terminal prohormone of brain natriuretic peptide;
PDE5i = phosphodiesterase-5 inhibitor.
PDE5i = phosphodiesterase-5 inhibitor; WHO FC = World Health Organization Functional Class.
PDE5i = phosphodiesterase-5 inhibitor.
¶Clinical worsening defined as death from any cause; hospitalization for worsening PAH (non-elective hospitalization due to PAH or initiation of parenteral prostanoid therapy); or disease progression (decrease in 6MWD ≥15% on two separate days plus either worsening WHO FC, need for new PAH-targeted medication, or decompensated right-sided heart failure).
Results from the REPLACE (Riociguat rEplacing PDE-5i therapy evaLuated Against Continued PDE-5i thErapy) study in adult patients with pulmonary arterial hypertension (PAH) (WHO Group 1) who were receiving PDE5i therapy and still at intermediate risk1
PDE5i = phosphodiesterase-5 inhibitor.
Includes symptomatic and asymptomatic hypotension.
Preferred term for worsening of the condition.
An additional death occurred in the safety follow-up period.
Adverse reactions (pooled from CHEST-1 and PATENT-1)2
GERD = gastroesophageal reflux disease.
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