The contribution of the soluble guanylate cyclase stimulator riociguat to changes in functional status and hemodynamic parameters in the combined approach to treating patients with inoperable chronic thromboembolic pulmonary hypertension

Objective: to study the contribution of the soluble guanylate cyclase stimulator riociguate to the overall effect of combined treatment of patients with inoperable chronic thromboembolic pulmonary hypertension.

Material and methods. The study included patients with an inoperable form of CTEPH who were treated with riociguat and underwent balloon pulmonary angioplasty (BPA). The patients were divided into 2 groups of 50 people "Riociguat+BPA" and "BPA+Riociguat". Patients of the "Riociguat+BPA" group received PAH-specific therapy with riociguat at the first stage of treatment, after which they underwent several sessions of BPA. Patients of the "BPA+Riociguat" group recieved a series of BPA, and then riociguat was initiated. Patients took riociguat for 6 months at a target dose of 7.5 mg/day in both groups. The average number of completed BPA sessions was 4. A control invasive measurement of hemodynamic parameters was performed at three points: before the start of treatment, after the first stage of treatment, and 6 months after the completion of the entire course of treatment.

Results. Following the administration of riociguat, there was a statistically significant increase in the 6MWT distance by 36 m in the “Riociguat+BPA” group and by 17 m in the “BPA+Riociguat” group. Improvement in key hemodynamic parameters was observed: in particular, after initiation of riociguat therapy, a decrease in mPAP by 6 mmHg and PVR by 1,97 Wood units was observed in the “Riociguat+BPA” group, while in the “BPA+Riociguat” group, a decrease in mPAP by 5 mmHg and PVR by 1,7 Wood units was observed. A smaller influence of riociguat was found with respect to gas exchange parameters. When comparing the results achieved at the end of the course of treatment, both groups demonstrated a good effect from the combined approach, regardless of which type of treatment was initiated first.

Conclusion. The contribution of riociguat is manifested in the improvement of the functional status and hemodynamic parameters both when prescribing the drug before a series of BPA sessions, and when adding the drug after endovascular treatment. The sequence of initiation of treatment methods within the framework of the combined approach should be determined individually.

1. Danilov N.M., Matchin Yu.G., Grankin D.S. et al. Russian consensus: balloon pulmonary angioplasty in treatment of chronic thromboembolic pulmonary hypertension. Eurasian heart journal. 2025;(1):30-49. (In Russ.) https://doi.org/10.38109/2225-16852025-1-30-49]

2. Chazova I.E., Martynyuk T.V., Avdeev S.N. et al. Expert consensus on approaches to risk stratification and choice of therapy in patients with inoperable and residual chronic thromboembolic pulmonary hypertension. Terapevticheskii arkhiv. 2025; 97.(3):279-288 (In Russ) https://doi.org/10.26442/00403660.2025.03.203237]

3. Chazova I.E., Martynyuk T.V., Shmalts A.A. et al. Eurasian guidelines for the diagnosis and treatment of pulmonary hypertension (2023). Eurasian heart journal. 2024;(1):6-85. (In Russ.)] https://doi.org/10.38109/2225-1685-2024-1-6-85

4. Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J.Oxford University Press. 2022;43(38):3618-3731. https://doi.org/10.1093/eurheartj/ehac237

5. Kim NH, D’armini AM, Delcroix M, et al. Chronic thromboembolic pulmonary disease. Eur Respir J. Published online 2024:2401294. https://doi.org/10.1183/13993003.01294-2024

6. Araújo P, Calé R, Pereira E, et al. Balloon pulmonary angioplasty and riociguat in the management of chronic thromboembolic pulmonary hypertension: a systematic review. Respir Med. 2025;244:108154. https://doi.org/10.1016/j.rmed.2025.108154

7. Pamukçu E, Kaya MO. Meta-Analysis of Real-World Clinical Practice to Assess the Effectiveness of Riociguat in Treating Chronic Thromboembolic Pulmonary Hypertension. The Journal of Clinical Hypertension. 2025;27(2):e70015. https://doi.org/10.1111/JCH.70015

8. Kim NH, D’Armini AM, Grimminger F, et al. Haemodynamic effects of riociguat in inoperable/recurrent chronic thromboembolic pulmonary hypertension. Heart. 2016;103(8):599-606. https://doi.org/10.1136/heartjnl-2016-309621

9. Kawakami T, Matsubara H, Shinke T, et al. Balloon pulmonary angioplasty versus riociguat in inoperable chronic thromboembolic pulmonary hypertension (MR BPA): an open-label, randomised controlled trial. Lancet Respir Med. 2022;10(10):949-960. https://doi.org/10.1016/S2213-2600(22)00171-0

10. Jaïs X, Brenot P, Bouvaist H, et al. Balloon pulmonary angioplasty versus riociguat for the treatment of inoperable chronic thromboembolic pulmonary hypertension (RACE): a multicentre, phase 3, open-label, randomised controlled trial and ancillary follow-up study. Lancet Respir Med. 2022;10(10):961-971. https:// doi.org/10.1016/S2213-2600(22)00214-4

11. Jain N, Sheikh MA, Bajaj D, et al. Periprocedural Complications With Balloon Pulmonary Angioplasty: Analysis of Global Studies. Cardiovascular Interventions. 2023;16(8):976-983. https://doi.org/10.1016/J.JCIN.2023.01.361

12. Dinevich E.O., Danilov N.M., Chazova I.E. The role of soluble guanylate cyclase stimulator riociguat in preventing the development of reperfusion lung injury after balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension. Systemic Hypertension. 2023;20(4):11-17. (In Russ.) https://doi.org/10.38109/2075-082X-2023-4-11-17]

13. Gerges C, Jevnikar M, Brenot P, et al. Effect of Balloon Pulmonary Angioplasty and Riociguat on Right Ventricular Afterload and Function in CTEPH: Insights from the RACE Trial. Circ Cardiovasc Interv. 2025;18(2):e014785. https://doi.org/10.1161/CIRCINTERVENTIONS.124.014785

14. Aoki T, Sugimura K, Terui Y, et al. Beneficial effects of riociguat on hemodynamic responses to exercise in CTEPH patients after balloon pulmonary angioplasty – A randomized controlled study. IJC Heart & Vasculature. 2020;29:100579. https://doi.org/10.1016/J.IJCHA.2020.100579