Adempas (riociguat) / Bayer, Merck (MSD) - LARVOL DELTA

Pleural Effusion Formation Linked to Altered Transporter Expression Involved in Alveolar Fluid Clearance: Insights From the Monocrotaline Model of Pulmonary Hypertension. (PubMed, Basic Clin Pharmacol Toxicol) - "This study investigates changes in alveolar fluid clearance (AFC) transporter expression in relation to lung fluid accumulation and PLEF formation during PAH progression, as well as the effects of terbutaline (TER) and riociguat (RIO) treatment...Conversely, RIO showed trends towards fluid accumulation, indicated by perivascular oedema in control animals and reduced oxygen saturation in MCT-treated rats. These findings support a potential role of impaired AFC in the pathogenesis of PLEF in PAH and suggest that pharmacological interventions may differentially affect lung fluid homeostasis in this setting."

Journal • Pleural effusion • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • ATP1B1

OPTIMIZING RIOCIGUAT THERAPY FOR PULMONARY HYPERTENSION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF DOSE VARIABILITY, SAFETY, AND EFFICACY (CHEST 2025) - No abstract available

Retrospective data • Review • Cardiovascular • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Treatment and monitoring of CTD-ILDs (ERS 2025) - "We describe recent advances in the treatment of CTD-ILD, including novel data and trials as well as post hoc analyses of clinical trials on mycophenolate, cyclophosmphamide, tocilizumab, rituximab, riociguat and nintedanib. Lastly, we elucidate on peripheral blood cell gene expression profiling as a novel way to identify patients with a better treatment response to mycophenolate."

Rheumatology

Differential effects of riociguat and vericiguat on pulmonary vessels and airways in precision-cut lung slices and in the isolated perfused rat lung (DGT 2025) - "Riociguat and vericiguat caused vasodilation of the pulmonary arteries in PCLS. In isolated lung perfusion, riociguat was significantly more potent than vericiguat, resulting in a 10% greater reduction in pulmonary arterial pressure. Neither riociguat nor vericiguat showed a significant effect on the pulmonary veins."

Preclinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • EDN1 • IL6

RIALTO: A Long-term Extension Study of Riociguat in Patients With Symptomatic Pulmonary Arterial Hypertension. (clinicaltrials.gov) - P4 | N=25 | Active, not recruiting | Sponsor: Bayer | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2025 ➔ Sep 2025 | Trial primary completion date: Dec 2025 ➔ Sep 2025

Enrollment closed • Trial completion date • Trial primary completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Investigational randomized controlled trial of patients with inoperable chronic thromboembolic pulmonary hypertension treated with riociguat vs selexipag (ESC-WCC 2025) - "Riociguat and selexipag was significantly effective in treatment naive patients with inoperable CTEPH. Selecting the drug based on the characteristics of each drug could contribute to more favorable result in patients with CTEPH."

Clinical • Cardiovascular • Pulmonary Embolism

Hemodynamic effects of add-on therapies in pulmonary arterial hypertension: an additive component network meta-analysis. (ESC-WCC 2025) - "Out of 1,974 identified studies, 12 RCTs (1,312 patients with baseline and follow-up right heart catheterization) met inclusion criteria. Most patients were WHO functional class II or III, with a baseline 6MWD of 375±85 meters. The effect of add-on therapies on PVR was -3.2 WU for ERA, -2.9 WU for sotatercept, -2.3 WU for riociguat, -2.1 WU for oral prostanoids, -2.0 WU for PDE5i, -1.2 WU for seralutinib, and -0.3 WU for inhaled prostanoids."

Retrospective data • Cardiovascular • Congestive Heart Failure • Heart Failure

Impact of medical therapy on balloon pulmonary angioplasty outcomes in chronic thromboembolic pulmonary hypertension (ESC-WCC 2025) - " Seventeen patients were treated with subcutaneous Treprostinil, 41 with Riociguat, and 24 did not receive medical therapy prior to BPA... Our findings indicate that pre-treatment with Treprostinil before BPA can significantly reduce right ventricular afterload in inoperable CTEPH patients, leading to similar final hemodynamic outcomes compared to those not receiving therapy. Treprostinil induced the largest hemodynamic improvements and could be safely discontinued in the majority of patients without affecting the overall BPA results."

Cardiovascular • Pulmonary Embolism

Switching sildenafil to riociguat in chronic thromboembolic pulmonary hypertension after balloon pulmonary angioplasty - the S2R study (ESC-WCC 2025) - "In patients with CTEPH who have completed BPA treatment, switching PDE5i to riociguat improved pulmonary haemodynamics and functional outcomes despite significant treatment-related adverse events. These findings support the use of riociguat for CTEPH patients after BPA."

Cardiovascular • Hypotension • Pulmonary Embolism

Safety and efficacy of macitentan and riociguat upfront combination therapy in patients with idiopathic pulmonary arterial hypertension at intermediate risk. (ESC-WCC 2025) - "These preliminary data support the safety and the efficacy of initial macitentan and riociguat combination therapy in patients with idiopathic PAH. Larger randomized trials are warranted to extend this approach to clinical practice."

Clinical • Combination therapy • Cardiovascular • NPPB

LEPHT: A Study to Test the Effects of Riociguat in Patients With Pulmonary Hypertension Associated With Left Ventricular Systolic Dysfunction (clinicaltrials.gov) - P2 | N=202 | Completed | Sponsor: Bayer | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CST3 • SPP1

Klippel-Trenaunay Syndrome with Chronic Thromboembolic Pulmonary Hypertension Treated with Balloon Pulmonary Angioplasty. (PubMed, Pneumologie) - "Da eine pulmonale Endarteriektomie nicht möglich war, wurde eine medikamentöse Behandlung mit Riociguat eingeleitet...Wir präsentieren diesen Fall, da bei KTS-Patienten Thromboembolien und die Entwicklung einer CTEPH berücksichtigt werden müssen. Therapeutische Optionen sind PEA-Operation, interventionelle BPA-Behandlung und medikamentöse Behandlung."

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Pulmonary Embolism • Respiratory Diseases

Myocardial cGMP-PKG1α dysregulation contributes to ventricular tachycardia pathogenesis in type II diabetes and metabolic syndrome. (PubMed, Heart Rhythm) - "In DMII and MBS, reduced cGMP-PKG1α signaling drives GSK3β hyperstimulation, calcium dyshomeostasis, and VT. Pharmacological modulation of these pathways opposes VT pathogenesis."

Journal • Cardiovascular • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • Ventricular Tachycardia • LEP • LEPR

Effect of riociguat on exercise following balloon pulmonary angioplasty in patients with inoperable chronic thromboembolic pulmonary hypertension in Japan (THERAPY-HYBRID-BPA): a multicentre, double-blind, randomised, controlled, phase 4 trial. (PubMed, Lancet Respir Med) - P2 | "Our findings suggested that the continuation of riociguat post-BPA might attenuate the worsening of exercise intolerance without increasing the risk of adverse events; discontinuation might require more careful consideration. These results should be explored in long-term studies."

Journal • P4 data • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Pulmonary Embolism • Respiratory Diseases

Pathogenesis, Diagnosis, and Management of Chronic Thromboembolic Pulmonary Hypertension. (PubMed, Card Electrophysiol Clin) - "The only potentially curative treatment for CTEPH is pulmonary endarterectomy However, approximately 40% of patients are inoperable. Currently, only Riociguat is Food and Drug Administration approved specifically for CTEPH, with additional drug trials underway."

Journal • Review • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Pulmonary Embolism • Respiratory Diseases

Predicting Response to Switching From Phosphodiesterase Type 5 Inhibitor to Riociguat in Patients With Pulmonary Arterial Hypertension: Biomarker and Responder Analysis of the RESPITE and REPLACE Studies. (PubMed, Pulm Circ) - "No baseline threshold value of any biomarker provided a good likelihood of predicting the response to riociguat. Overall, the biomarkers evaluated did not help to identify patients who were more likely to respond to switching from PDE5is to riociguat."

Biomarker • Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • GDF15

Impact of Multiple Doses of BAY63-2521 on Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Patients With Interstitial Lung Disease (ILD) Associated Pulmonary Hypertension (PH) (clinicaltrials.gov) - P2 | N=22 | Completed | Sponsor: Bayer | Active, not recruiting ➔ Completed | Trial completion date: Oct 2025 ➔ Jul 2025 | Trial primary completion date: Oct 2025 ➔ Jul 2025

Trial completion • Trial completion date • Trial primary completion date • Cardiovascular • Hypertension • Interstitial Lung Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

PATENT-CHILD: Riociguat in Children With Pulmonary Arterial Hypertension (PAH) (clinicaltrials.gov) - P3 | N=24 | Active, not recruiting | Sponsor: Bayer | Trial completion date: Jul 2026 ➔ Aug 2027

Trial completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Assessing the role of endothelium-protective drugs: Functional and molecular insights into chronic thromboembolic pulmonary hypertension derived endothelial cells. (PubMed, Biomed Pharmacother) - "Therapeutic approaches targeting endothelial dysfunction and the NO/sGC pathway in CTEPH partially restore endothelial function, highlighting the dual action of Riociguat and Sildenafil, stimulating sGC while exerting upstream effects by enhancing eNOS signaling. These findings underscore the importance of targeted pharmacological approaches to improve patient outcomes."

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Pulmonary Embolism • Respiratory Diseases • NOS3

A management of a patient with chronic thromboembolic pulmonary hypertension prior to surgical resection for lung cancer. (PubMed, Respir Med Case Rep) - "We prioritized the treatment of CTEPH, starting oral riociguat followed by BPA three times...This case report presents a method for managing both CTEPH and primary lung cancer. The essence was the intensification of CTEPH treatment in anticipation of lobectomy."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Arterial Hypertension • Pulmonary Disease • Pulmonary Embolism • Respiratory Diseases • Solid Tumor

Successful upfront combination therapy against pulmonary arterial hypertension associated with unilateral absence of the pulmonary artery: a case report. (PubMed, Eur Heart J Case Rep) - "Therefore, triple therapy with macitentan (10 mg), selexipag (0.4 mg), and riociguat (3 mg) was initiated...One year later, due to recurrent dyspnoea on light exertion, iloprost inhalation therapy was initiated. The patient has since progressed well, maintaining WHO class II during a 7-year follow-up period. Prostacyclin inhalation combined with triple therapy can be an effective treatment strategy for patients with UAPA-associated pulmonary arterial hypertension."

Journal • Acute Coronary Syndrome • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Sleep Apnea • Sleep Disorder

Rheumatologists' Adherence to EULAR Recommendations for Systemic Sclerosis Treatment: Experience of a Single Center in Serbia. (PubMed, J Clin Med) - "Medications such as iloprost, phosphodiesterase type 5 (PDE-5) inhibitors, fluoxetine, and bosentan, recommended for the treatment of RP and digital ulcers, were not approved for SSc by the Republic Health Insurance Fund. Treatment for pulmonary arterial hypertension (PAH) was administered to only 16 patients (4.2%), including 2 who received bosentan, 10 who received PDE-5 inhibitors, and 4 who were treated with riociguat...Cyclophosphamide was consistently prescribed for interstitial lung disease (ILD), with an increased frequency observed after the guideline update. No significant differences were observed in the use of methotrexate for skin involvement, ACE inhibitors for scleroderma renal crisis, or antibiotics for gastrointestinal symptoms... Rheumatologists' adherence to the EULAR/EUSTAR guidelines varied considerably, with 25% to 100% of eligible patients receiving the recommended treatments. Concordance improved in the management of PAH, ILD, and..."

Journal • Cardiovascular • Hypertension • Immunology • Interstitial Lung Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Rheumatology • Scleroderma • Systemic Sclerosis

RIVERII: Effects of Riociguat on RIght VEntricular Size and Function in PAH and CTEPH (clinicaltrials.gov) - P4 | N=30 | Active, not recruiting | Sponsor: Heidelberg University | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2026 ➔ Aug 2025 | Trial primary completion date: Mar 2026 ➔ Jul 2025

Enrollment closed • Trial completion date • Trial primary completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Pulmonary Embolism • Respiratory Diseases

ESRA: Efficacy and Safety of Riociguat in Incipient Pulmonary Vascular Disease as an Indicator for Early PAH (clinicaltrials.gov) - P2 | N=70 | Active, not recruiting | Sponsor: Heidelberg University | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2026 ➔ Jul 2025 | Trial primary completion date: Oct 2025 ➔ Jul 2025

Enrollment closed • Trial completion date • Trial primary completion date • Cardiovascular • Hypertension • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis

New horizons in systemic sclerosis treatment: advances and emerging therapies in 2025. (PubMed, RMD Open) - "While recent EULAR recommendations have updated the standard of care for SSc, the field is rapidly evolving with novel therapeutic strategies and precision medicine approaches.Traditional immunosuppressive therapies-including mycophenolate mofetil, cyclophosphamide and rituximab-remain essential for controlling skin and lung involvement while autologous haematopoietic stem cell transplantation offers a proven disease-modifying option for selected high-risk patients. Tocilizumab and nintedanib have established roles in lung preservation in SSc-associated interstitial lung disease (SSc-ILD). In pulmonary arterial hypertension (PAH), early combination therapy with endothelin receptor antagonists and phosphodiesterase-5 inhibitors, complemented by newer agents such as selexipag and riociguat, has improved survival and quality of life. Advances in gastrointestinal, renal and musculoskeletal management continue to evolve, with promising roles for intravenous immunoglobulin and..."

IO biomarker • Journal • Review • Bone Marrow Transplantation • Cardiovascular • Fibrosis • Gastrointestinal Disorder • Hypertension • Immunology • Interstitial Lung Disease • Musculoskeletal Diseases • Peptic Ulcer • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Rheumatology • Scleroderma • Systemic Sclerosis • Transplantation