Study results

The REPLACE study results

The REPLACE study met its primary endpoint. Switching from PDE5i to riociguat resulted in a significantly higher proportion of patients experiencing clinical improvement and significantly lower rates of clinical worsening compared with remaining on PDE5i.
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The REPLACE study results presentation

On behalf of the REPLACE investigators, Professor Marius Hoeper presents the findings of REPLACE.

In this video summary, Professor Hoeper discusses the study rationale and design, results data, and clinical implications of the study.

Overview of key findings

Patients switching from PDE5i to riociguat had a significantly higher likelihood of clinical improvement and significantly reduced rate of clinical worsening compared with patients remaining on PDE5i

Primary endpoint

Secondary endpointsa

Secondary endpoint


Risk profiles at Week 24

• REPLACE is the first randomized, controlled study in patients with PAH investigating switching within the same pathway, and also the first head-to-head RCT of approved PAH therapies
• Riociguat was generally well tolerated in patients who switched from PDE5i. Overall AE rates were similar between the treatment groups, with a higher incidence of SAEs in the PDE5i group
• REPLACE demonstrated that switching from PDE5i (± ERA) to riociguat can benefit patients with PAH at intermediate risk and can serve as a strategic option for treatment escalation
• By optimizing the NOsGCcGMP pathway by switching from PDE5i to riociguat, patients can remain on monotherapy or dual combination therapy, delaying the addition of further therapies to a later stage
aSecondary endpoints were not powered to show an effect.
bThe risk profiles for the patient groups were similar at baseline.
cThe French non-invasive scale refers to the number of parameters in the low risk range.

Rationale & study design

Learn about the REPLACE study rationale and design

Study summary

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See the final video presentation, for the final summary


Find resources associated with the study, including other riociguat publications

Hoeper MM et al Eur Respir J 2020 Vol 56 suppl 63, e-poster presented at the 2020 European Respiratory Society Virtual Congress

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