Haemodynamic effects of riociguat in inoperable/recurrent chronic thromboembolic pulmonary hypertension.

We compared the haemodynamic effects of riociguat in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent/recurrent CTEPH after pulmonary endarterectomy in the Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase-Stimulator Trial 1 study. Patients with inoperable or persistent/recurrent CTEPH (n=261; mean± SD age 59±14 years; 66% women) were randomised to riociguat (up to 2.5 mg three times daily) or placebo. Haemodynamic parameters were assessed at baseline and week 16. Riociguat decreased pulmonary vascular resistance (PVR) in inoperable (n=189; least-squares mean difference: -285 dyn s/cm5 (95% CI -357 to -213); p<0.0001) and persistent/recurrent (n=72; -131 dyn s/cm5 (95% CI -214 to -48); p=0.0025) patients. Cardiac index improved in inoperable patients by a least-squares mean difference of +0.6 L/min/m2 (95% CI 0.4 to 0.7; p<0.0001), while in persistent/recurrent patients the change was +0.2 L/min/m2 (95% CI -0.1 to 0.5; p=0.17). Mean pulmonary artery pressure decreased in inoperable and persistent/recurrent patients(-4.7 mm Hg (95% CI -6.9 to -2.6; p<0.0001 and -4.8 mm Hg (-8.2 to -1.5; p=0.0055), respectively). For all patients, changes in 6 min walk distance correlated with changes in PVR (r=-0.29 (95% CI -0.41 to -0.17); p<0.0001) and cardiac index (r=0.23 (95% CI 0.10 to 0.35); p=0.0004). Riociguat improved haemodynamics in patients with inoperable CTEPH or persistent/recurrent CTEPH. NCT00855465.

Kim NH ，D'Armini AM ，Grimminger F ，Grünig E ，Hoeper MM ，Jansa P ，Mayer E ，Neurohr C ，Simonneau G ，Torbicki A ，Wang C ，Fritsch A ，Davie N ，Ghofrani HA ... -  《-》

Riociguat for the treatment of chronic thromboembolic pulmonary hypertension.

Ghofrani HA ，D'Armini AM ，Grimminger F ，Hoeper MM ，Jansa P ，Kim NH ，Mayer E ，Simonneau G ，Wilkins MR ，Fritsch A ，Neuser D ，Weimann G ，Wang C ，CHEST-1 Study Group ... -  《-》

Bosentan for treatment of inoperable chronic thromboembolic pulmonary hypertension: BENEFiT (Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension), a randomized, placebo-controlled trial.

Jaïs X ，D'Armini AM ，Jansa P ，Torbicki A ，Delcroix M ，Ghofrani HA ，Hoeper MM ，Lang IM ，Mayer E ，Pepke-Zaba J ，Perchenet L ，Morganti A ，Simonneau G ，Rubin LJ ，Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension Study Group ... -  《-》

Pharmacological therapy for patients with chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but life-threatening disease resulting from unresolved thromboembolic obstructions. Pulmonary endarterectomy (PEA) surgery is the gold-standard treatment as it is potentially curative; however, not all patients are deemed operable and up to one-third have persistent or recurrent CTEPH after the procedure. Pulmonary arterial hypertension (PAH) and CTEPH have similar clinical presentations and histopathological features, so agents shown to be effective in PAH have often been prescribed to patients with CTEPH in the absence of proven therapies. However, clinical evidence for this strategy is not compelling. A number of small uncontrolled trials have investigated endothelin receptor antagonists, prostacyclin analogues and phosphodiesterase type 5 inhibitors in CTEPH with mixed results, and a phase III study of the endothelin receptor antagonist bosentan met only one of its two co-primary end-points. Recently, however, the soluble guanylate cyclase stimulator, riociguat, was approved in the USA and Europe for the treatment of inoperable or persistent/recurrent CTEPH following positive results from the phase III CHEST study (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase-Stimulator Trial). This article reviews the current evidence for the use of pharmacological therapies in CTEPH.

Hoeper MM 《-》

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry.

The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits and collated via case report forms. In total, 956 patients with CTEPH were included in the analysis. The most common AEs in these patients were peripheral edema/edema (11.7%), dizziness (7.5%), right ventricular (RV)/cardiac failure (7.7%), and pneumonia (5.0%). The most common SAEs were RV/cardiac failure (7.4%), pneumonia (4.1%), dyspnea (3.6%), and syncope (2.5%). Exposure-adjusted rates of hemoptysis/pulmonary hemorrhage and hypotension were low and comparable to those in the long-term extension study of riociguat (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase-Stimulator Trial [CHEST-2]). Data from EXPERT show that in patients with CTEPH, the safety of riociguat in routine practice was consistent with the known safety profile of the drug, and no new safety concerns were identified.

Ghofrani HA ，Gomez Sanchez MA ，Humbert M ，Pittrow D ，Simonneau G ，Gall H ，Grünig E ，Klose H ，Halank M ，Langleben D ，Snijder RJ ，Escribano Subias P ，Mielniczuk LM ，Lange TJ ，Vachiéry JL ，Wirtz H ，Helmersen DS ，Tsangaris I ，Barberá JA ，Pepke-Zaba J ，Boonstra A ，Rosenkranz S ，Ulrich S ，Steringer-Mascherbauer R ，Delcroix M ，Jansa P ，Šimková I ，Giannakoulas G ，Klotsche J ，Williams E ，Meier C ，Hoeper MM ，NEW COLLABORATORS LIST ... -  《-》