riociguat / Generic mfg. - LARVOL DELTA

PATENT-CHILD: Riociguat in Children With Pulmonary Arterial Hypertension (PAH) (clinicaltrials.gov) - P3 | N=24 | Active, not recruiting | Sponsor: Bayer | Trial completion date: Aug 2027 ➔ May 2028

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

Effective arterial elastance relates more closely to pulsatile than resistive indices during routine haemodynamic assessment of inoperable chronic thromboembolic pulmonary hypertension. (PubMed, ERJ Open Res) - "Total PA stiffness was the strongest linear correlate of total PA load, reflected by effective arterial elastance, and thus a key contributor to RV-PA uncoupling at baseline and after treatment (balloon angioplasty or riociguat) in inoperable CTEPH https://bit.ly/4wvje3V."

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

Riociguat as inpatient rescue therapy for acute decompensation of inoperable chronic thromboembolic pulmonary hypertension. (PubMed, BMJ Case Rep) - "He was discharged on rivaroxaban and referred to the heart failure and respiratory clinic. Subsequent right heart catheterisation confirmed inoperable CTEPH. He was reviewed at the National Pulmonary Hypertension Clinic, and following multidisciplinary discussion, given insufficient surgically accessible thromboembolic burden and coexisting left ventricular dysfunction, the decision was made to continue riociguat as long-term medical therapy."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Pulmonary Embolism • Respiratory Diseases

Endothelial Cell Transcriptomics Reveal Activation of Ribosomal-related Pathways in Chronic Thromboembolic Pulmonary Hypertension. (PubMed, Arch Bronconeumol) - "Dysregulated protein biosynthesis is a characteristic feature of CTEPH, distinguishing them from PAH. Our findings highlight a coordinated translation-mitochondria-MAM axis potentially involved in endothelial dysfunction and vascular remodelling, supporting the need for therapies targeting disease-specific molecular pathways beyond soluble guanylate cyclase stimulation."

Journal • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Pulmonary Embolism • Respiratory Diseases

Residual pulmonary hypertension after pulmonary endarterectomy or balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension – insights from the New International Chronic Thromboembolic Pulmonary Hypertension Database (ERS 2026) - P=N/A | "In both groups, riociguat monotherapy was most frequent...However, during the observational period, PEA programs were well established, whereas BPA programs were at an early stage outside Japan. Table: FC by mPAP at first RHC post PEA/BPA Post PEA Post BPA mPAP <25 mmHg ≥25 mmHg <25 mmHg ≥25 mmHg FC I/II 92% 79% 100% 79%"

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

IMPACT OF RIOCIGUAT ON HOSPITALIZATION IN PATIENTS WITH CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION (CHEST 2026) - No abstract available

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

OPTIMIZING RIOCIGUAT THERAPY FOR PULMONARY HYPERTENSION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF DOSE VARIABILITY, SAFETY, AND EFFICACY (CHEST 2026) - No abstract available

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

EFFICACY AND SAFETY OF RIOCIGUAT IN PULMONARY HYPERTENSION WITH CARDIAC DYSFUNCTION: A SYSTEMATIC REVIEW AND META-ANALYSIS (CHEST 2026) - No abstract available

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

EPIPHANY: Effects of Combination Medical Therapy Followed by BPA on Right Ventricular-PA Coupling and Hemodynamics in CTEPH (clinicaltrials.gov) - P3 | N=7 | Terminated | Sponsor: Dr Sudarshan Rajagopal | N=15 ➔ 7 | Trial completion date: Dec 2026 ➔ May 2026 | Recruiting ➔ Terminated | Trial primary completion date: Dec 2026 ➔ Mar 2026; Sponsor Requested

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

Targeting Novel Pathways in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis of New Therapeutic Agents. (PubMed, Niger Med J) - "Udenafil and fasudil showed modest benefits, while anastrozole had mixed results with possible sex-specific effects. At the individual trial level, sotatercept (0.7 mg/kg), riociguat (2.5 mg), and metformin (500 mg with bosentan) showed the most favourable benefit profiles. Standardised trial designs and consistent outcome reporting are needed to confirm these potential disease-modifying effects."

Journal • Retrospective data • Cardiovascular • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Soluble guanylate cyclase stimulators and activators: Chemistry, biology, and therapeutic advances. (PubMed, Eur J Med Chem) - "Although first-in-class sGC stimulators (e.g., riociguat, vericiguat) and activators (e.g., cinaciguat) have advanced into clinical use or development, most subsequent candidates continue to be refined to optimize efficacy, safety, and target selectivity. Specifically, these small molecules are classified and elaborated based on their mechanisms of action, structural characteristics, and development trajectories; for each category, the binding modes, structural features, and pharmacological activities of representative compounds are analyzed in detail, while their inherent advantages and limitations are critically evaluated. Collectively, this review offers valuable insights and guidance for the future research and development of safer, more effective, and more precisely targeted sGC modulators."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetic Retinopathy • Heart Failure • Hypertension • Nephrology • Pulmonary Arterial Hypertension • Pulmonary Disease • Renal Disease • Respiratory Diseases • Retinal Disorders

Comparable exercise hemodynamic improvements with riociguat and selexipag under multimodal therapy including balloon pulmonary angioplasty in inoperable chronic thromboembolic pulmonary hypertension (ESC 2026) - "In patients with inoperable CTEPH undergoing multimodal treatment including BPA, both riociguat and selexipag significantly improved resting and exercise hemodynamics. Selexipag demonstrated efficacy comparable to riociguat, suggesting that effective hemodynamic improvement can also be achieved with selexipag in this clinical setting."

Cardiovascular • Pulmonary Embolism

Extended prospective follow-up of a randomised comparison of riociguat and selexipag under multimodal therapy in inoperable chronic thromboembolic pulmonary hypertension (ESC 2026) - "The mean pulmonary arterial pressure–cardiac output slope decreased from baseline to post-BPA in both groups (riociguat: 11.59 [IQR 6.91–16.68] to 4.4 [3.74–7.94]; selexipag: 9.87 [6.76–14.9] to 4.68 [4.02–5.88]; both p = 0.031).ConclusionBoth riociguat and selexipag demonstrated significant hemodynamic improvements in treatment-naïve patients with inoperable CTEPH before and after BPA. Selexipag showed efficacy comparable to riociguat within a multimodal treatment strategy, supporting its role as an effective pulmonary vasodilator in this setting."

Clinical • Cardiovascular • Pulmonary Embolism

Impaired arterial baroreflex function as a potential mechanism for riociguat-induced hypotension: insights from a baroreflex open-loop analysis in sugen–hypoxia pulmonary hypertension rats (ESC 2026) - "However, it may also induce systemic hypotension, which could be accompanied by a reduction in baroreflex operating-point gain. Under riociguat-induced hypotension, the reduction in SVR cannot be adequately buffered due to impaired baroreflex function, potentially resulting in prolonged hypotension."

Preclinical • Reflex • Cardiovascular • Hypotension • Pulmonary Embolism

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 | Terminated | Sponsor: Bayer | Completed ➔ Terminated; The sponsor terminated the study for strategic reasons. This decision was not due to safety concerns for participants receiving treatment at the time the study was terminated.

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

PHoenix: Pulmonary Hypertension: Intensification and Personalisation of Combination Rx (clinicaltrials.gov) - P4 | N=70 | Active, not recruiting | Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust | Recruiting ➔ Active, not recruiting | N=40 ➔ 70 | Trial completion date: Jan 2027 ➔ Jan 2028 | Trial primary completion date: Jan 2027 ➔ Jan 2028

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

STOP-RIO study: protocol for a randomised, controlled, open-label non-inferiority trial to test the safety of discontinuation of riociguat after balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension. (PubMed, BMJ Open) - "Results will be disseminated through peer-reviewed publication and shared with patient organisations and scientific congress. EU Clinical Trials Register: 2024-5 19 225-38-00."

Clinical protocol • Head-to-Head • Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Pulmonary Embolism • Respiratory Diseases

Exploring the therapeutic landscape of pulmonary hypertension associated with interstitial lung disease, with a focus on idiopathic pulmonary fibrosis: a narrative review. (PubMed, Front Pharmacol) - "Most pulmonary arterial hypertension therapies have failed to show benefit in PH-IPF or have raised safety concerns, with ambrisentan and riociguat associated with harm. Inhaled treprostinil is currently the only approved therapy with randomized evidence of efficacy in PH associated with interstitial lung disease, including IPF. Supportive care, optimization of comorbidities, referral to expert centers, and timely lung transplantation evaluation remain essential components of management."

Journal • Review • Cardiovascular • Fibrosis • Hypertension • Idiopathic Pulmonary Fibrosis • Immunology • Infectious Disease • Interstitial Lung Disease • Pneumonia • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Transplantation

The Therapeutic Efficacy of Drugs Targeting the NO-sGC-cGMP Pathway in Treatment of Patients With Chronic Thromboembolic Pulmonary Hypertension: A Systematic Review. (PubMed, Pulm Circ) - "Pharmacological agents targeting the NO-sGC-cGMP pathway, particularly riociguat and sildenafil, demonstrate consistent improvements in exercise capacity, pulmonary hemodynamics, functional status, and biomarkers in patients with CTEPH...Nevertheless, further large-scale, high-quality randomized controlled trials are warranted to strengthen the evidence base and optimize treatment strategies. Systematic review registration: CRD42024510274, https://www.crd.york.ac.uk/PROSPERO/view/CRD42024510274."

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

Effects of riociguat on right ventricular size and function in pulmonary arterial hypertension (RIVER II): a prospective, phase IV study. (PubMed, Respir Res) - P4 | "Riociguat therapy resulted in a statistically significant improvement in right ventricular and atrial size and function with further improvements in exercise capacity and functional class. This prospective trial confirms the findings of previous retrospective studies and supports riociguat as an effective treatment option to improve RV geometry and performance."

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

Sepsis reporting signals associated with endothelin receptor antagonists and IFITM3-Centered interferon-responsive monocyte features: a pharmacovigilance and transcriptomic study. (PubMed, Front Pharmacol) - "FAERS analysis identified Maitentan and ambrisentan as PAH-targeted therapies with positive reporting signals for the MedDRA Preferred Term "Sepsis," with adjusted reporting associations persisting after adjustment for available demographic variables. These findings should be interpreted as reporting associations and transcriptomic hypotheses rather than evidence of causal drug-induced sepsis. The predicted riociguat-IFITM3 interaction provides a computational hypothesis for future experimental validation."

Adverse events • Journal • Cardiovascular • Hypertension • Infectious Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Septic Shock • IFIT1 • IFITM3 • IFNG • ISG15

Pharmacovigilance assessment of gout: a real-world study using the FAERS database. (PubMed, Front Pharmacol) - "These include Lenalidomide, Sacubitril valsartan, Ruxolitinib, Treprostinil, Octreotide, Selexipag, Rosuvastatin, Sitagliptin, Riociguat, Epoprostenol, Patiromer, Dasabuvir ombitasvir paritaprevir ritonavir, Tafamidis, Sparsentan, and Iloprost. These findings suggest the potential for targeted monitoring of drug-associated gout in clinical practice. When administering these medications, it may be crucial to regularly assess patients' uric acid levels and maintain heightened awareness for the possible onset of gout."

Adverse events • Journal • Real-world evidence • Cardiovascular • Gout • Hematological Disorders • Hematological Malignancies • Hypertension • Inflammatory Arthritis • Oncology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Rheumatology

Towards an integrated and proactive management of pulmonary hypertension in systemic sclerosis: a practical approach for early diagnosis and optimal patient management. (PubMed, Rheumatol Adv Pract) - "In SSc patients already receiving a dual combination, escalation to triple therapy including selexipag, or in selected cases switching to riociguat, should be promptly considered. Structured referral networks, implementation of the DETECT algorithm and involvement of a dedicated case manager and/or nurse can further improve timely diagnosis and continuity of care. Optimizing SSc-PAH management requires a proactive, integrated approach that bridges rheumatology and cardiology expertise."

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

Role of ROS, Soluble Guanylate Cyclase and cGMP in Mouse Lung Development During Hyperoxia. (PubMed, Am J Physiol Heart Circ Physiol) - "Those cells demonstrated impaired sGC-cGMP responsiveness to an NO donor, a response prevented by the cytosolic glutathione mimetic ebselen as well as by the sGC activator, cinaciguat, but not by mitochondrial matrix-targeted ebselen or by expression of an H2O2 scavenger in the mitochondrial intermembrane space (IMS-Prdx5). Neonatal mice exposed to 75% O2 for 2 weeks exhibited alveolar simplification and pulmonary artery (PA) wall thickening that were not rescued by cinaciguat or the sGC stimulator, riociguat...Collectively these studies demonstrate that separate mechanisms underlie the effects of hyperoxia on cGMP signaling and alveolarization in the newborn lung, with cytosolic oxidant stress responsible for impairing cGMP signaling and mitochondrial matrix ROS mediating the hyperoxia-induced impairment in lung alveolar development. Hence, the impairments in cGMP signaling and lung alveolar development during hyperoxia involve oxidant stress in distinct subcellular..."

Journal • Preclinical • Bronchopulmonary Dysplasia • Psychiatry • Pulmonary Disease • Respiratory Diseases • AVEN

Synergistic modulation of cAMP and cGMP rescues hemin-induced plasma membrane fragmentation. (PubMed, J Biol Chem) - "We found that pharmacological modulation of these pathways via NO donors (DEA/NO), soluble guanylyl cyclase (sGC) stimulators (riociguat) or IP receptor agonists (PGE1), and phosphodiesterase (PDE) inhibitors (PDE-5 inhibitor: sildenafil, PDE-3 inhibitor: ibudilast), phosphorylate the downstream vasodilator-stimulated phosphoprotein (VASP) and inhibit hemin-induced platelet activation and degranulation. In comparison, the PGE1-induced cAMP synthesis was enhanced in the presence of hemin. In conclusion, high concentrations of hemin change the cGMP and cAMP synthesis induced by their associated stimulators, while promoting plasma membrane destruction, which can be significantly inhibited by the simultaneous administration of riociguat DEA/NO and PGE1."

Journal • Thrombosis