CLINICAL CASE OF REPLACEMENT OF ENDOTHELIN RECEPTOR ANTAGONIST (BOSENTAN) BY SOLUBLE GUANYLATE CYCLASE STIMULATOR (RIOCIGUAT) IN THE PATIENT WITH PULMONARY ARTERIAL HYPERTENSION

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by progressive increase in pulmonary vascular resistance (PVR), higher pulmonary arteries mean pressure (mPAP), decrease in cardiac minute output (CMO) and other hemodynamic, functional and biochemical disorders. Existing PAH therapeutic algorithm, described in the European and Russian clinical guidelines, mainly suggest strategy of sequential combination therapy in the case of inadequate response to initial monotherapy. At this, switching from one PAH-specific drug to another is studied to a lesser extent. At the present similar approach (switching) has already been tested, for example, in switching from one endothelin receptor antagonist (ERA) to another, or from phosphodiesterase type 5 inhibitor (iPDE-5) to soluble guanylate cyclase stimulator (sGC). There are virtually no data about change of monotherapy when drugs target different molecular pathways of vascular tone regulation, in particular, in the pulmonary circulation vessels. This article describes clinical case of female patient with FC III pulmonary arterial hypertension (WHO) switched from therapy by endothelin-1 receptor antagonist (bosentan) to soluble guanylate cyclase stimulator (riociguat). Female, 37 years old, with verified by the right heart catheterization (RHC) diagnosis of idiopathic PAH (iPAH) received PAH-specific monotherapy of bosentan. Due to condition deterioration on the background of bosentan dose increase, medical conference decided to switch this patient to another class of PAH-specific therapy (sGC stimulator riociguat) with consequent follow-up. As a result of such approach positive changes in patient's condition, improvement of hemodynamic parameters, increased tolerance of physical exercise was demonstrated in comparison with previous therapy. This clinical case demonstrates safe and successful transfer from bosentan to riociguat in the patient with idiopathic PAH. Similar tactic for the change of therapy should be studied in further clinical trials.

pulmonary hypertension, pulmonary arterial hypertension, riociguat, bosentan, therapy

1. Russian clinical guidelines for the diagnosis and treatment of pulmonary hypertension 2016. Russian Medical Society for Arterial Hypertension. Link: http://cr.rosminzdrav.ru/#!/schema/136 [in Russian].

2. Chazova IE, Avdeev SN, Tsareva NA, Volkov AV, Martynyuk TV, Nakonechnikov SN Clinical recommendations for the diagnosis and treatment of pulmonary hypertension. Therapeutic archive. 2014; 9: 4-23 [in Russian].

3. Galie N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS). EurRespir J. 2015; 46(4):903-75.

4. MM Hoeper, HJ Bogaard, R. Condliffe et al. Definitions and Diagnosis of Pulmonary Hypertension. J Am Coll Cardiology. 2013; Vol. 62, Suppl D: D42–50.

5. D’Alonzo GE et al. Survival in Patients with Primary Pulmonary Hypertension Ann Intern Med 1991;115:343–349.

6. Galie N, Hoeper MM, Humbert M et al. Guidelines for the diagnosis and treatment of pulmonary hypertension: the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J. 2009;30:2493–2537.

7. McLaughlin VV, Archer SL, Badesch DB et al. ACCF/AHA 2009expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association. Circulation. 2009;119:2250–2294

8. Humbert M, Ghofrani H-A. The molecular targets of approved treatments for pulmonary arterial hypertension. Thorax. 2016;71:73-83.

9. Evgenov OV, Pacher P, Schmidt PM et al. NO-independent stimulators and activators of soluble guanylate cyclase: discovery and therapeutic potential. Nat Rev Drug Discov. 2006;5:755–68.

10. Ghofrani HA et al. Riociguat for the Treatment of Pulmonary Arterial Hypertension. N Engl J Med, 2013, 369:330-40. (DOI: 10.1056/NEJMoa1209655) + Protocol + Supplementary appendix.

11. Simonneau G, Gatzoulis MA, Adatia I, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 suppl D):34D–41D.

12. Tuder RM, Archer SL, Dorfmüller P, et al. Relevant issues in the pathology and pathobiology of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 suppl D):4D–12D.

13. Chazova I.Ye., Martynyuk T.V. Pulmonary hypertension. М.: Practice, 2015 [in Russian].

14. Adempas. Instructions for the medical use of the medicinal product. LP-002639-051017. Source: http://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=8bea0e5bb5d6-4154-b047-f667ce7430d7&t [in Russian].

15. Verdecchia A, Francisci S, Brenner H et al. Recent cancer survival in Europe: a 2000–02 period analysis of EUROCARE-4 data. Lancet Oncol/ 2007;8:784–796.

16. Ghofrani HA, Galie N, Grimminger F et al. Riociguat for the treatment of pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled study (PATENT-1). Chest. 2013, Atlanta GA, USA, 26–31 October 2013.

17. Rubin L, Galie N, Grimminger F et al. Riociguat for the treatment of pulmonary arterial hypertension (PAH): a phase III longterm extension study (PATENT-2). Am J Resp Crit Care Med. 2013;187:A3531.

18. Hossein-Ardeschir Ghofrani et al. Predictors of long-term outcomes in patients treated with riociguat for pulmonary arterial hypertension: data from the PATENT-2 open-label, randomised, long-term extension trial. Lancet Respir Med. 2016; 4:361–371.

19. D’Alonzo GE, Barst RJ, Ayres SM et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med. 1991;115:343-349.

20. Thenappan T, Shah SJ, Rich S et al. Survival in pulmonary arterial hypertension: a reappraisal of the NIH risk stratification equation. Eur Respir J. 2010;35:1079–1087.