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PAH: treatment

riociguat group 10/490 (2.0%) vs 2/214 (0.9%) in placebo group, with one patient in riociguat group having a fatal outcome. In addition, pulmonary haemorrhage (3/642, 0.5%) occurred during the long-term extension period and all of them had a fatal outcome. During the study, the dose of the study drug was decreased in 18 patients (10%) in the riociguat group.

In PH associated with chronic obstructive pulmonary diseases

The impact of a riociguat single dose25 was

assessed on haemodynamics, gas exchange, and lung function in 22 patients with PH associated with chronic obstructive pulmonary disease (COPD) receiving riociguat 1 or 2.5mg during right heart catheterisation. Riociguat caused significant improvements in mPAP (1mg: –11%; 2.5mg: –15%) and PVR (1mg: –15%; 2.5mg: –33%). No relevant changes in lung function or gas exchange were observed. Single doses of riociguat were well-tolerated and showed promising haemodynamic effects without changes of gas exchange or lung function.

In symptomatic PH associated with left ventricular systolic dysfuntion In LEPHT study26

administration of

riociguat at doses of 0.5–2.0 mg for 16 weeks did not result in statistically significant improvements in mPAP compared with placebo in patients with symptomatic PH associated with left ventricular systolic dysfunction. However, treatment in the 2.0mg target-dose arm (compared with placebo) resulted in consistent improvements in other haemodynamic parameters measured invasively and by echocardiography (left ventricular ejection fraction).

In PH associated with preserved left heart failure (HFpEF)

The acute haemodynamic effects27 of 26

riociguat were analysed in clinically stable patients with PH and HFpEF (left ventricular ejection fraction > 50%, mPAP ≥ 25mm Hg, and pulmonary arterial wedge pressure (PAWP) >15 mmHg). The patients were randomised to single oral doses of placebo or riociguat (0.5, 1, or 2mg). Riociguat resulted with no significant change in peak decrease in mPAP compared with placebo after six hours. However, riociguat 2mg significantly increased stroke volume (+9 ml; p=0.04) and decreased systolic blood pressure (–12 mmHg; p=0.03) and right

ventricular end-diastolic area (–5.6cm2


p=0.04), without significantly changing heart rate, PAWP, transpulmonary pressure gradient, or PVR. In patients with HFpEF and PH, riociguat showed no significant effect on haemodynamics, but it improved exploratory haemodynamic and echocardiographic parameters.


Riociguat is an efficacious treatment for PAH and CTEPH. The US Food and Drug Administration approved riociguat (Adempas®

, Bayer) on 8 October 2013. It

is indicated for the treatment of adult patients with inoperable or persistent/ recurrent CTEPH after PEA, and adult patients with PAH. European Medicines Agency’ approval was granted in March 2014. Currently it is the only treatment approved in both indications: PAH and adult patients with inoperable or persistent/recurrent CTEPH after PEA. l

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