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CTEPH: treatment


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Patent-1 RCT


Patent-2 open label study


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8 Figure 2: Effect of riociguat therapy on 6MWD in PAH patients Safety and tolerability


With respect to safety and tolerability, in CHEST-2, three cases of haemoptysis were reported at years 1 and 2 (one mild, one moderate and one severe). No cases were considered to be study drug-related.17 Data from the PATENT-1 and PATENT-2 study did report haemoptysis in five patients; however, no cases of haemoptysis were considered to be related to riociguat treatment. One out of two occurrences of pulmonary haemorrhage was considered related to the study drug.18 In addition to the two study drug-related severe adverse events that were fatal in the first year of PATENT-2 (one of PAH and one of pulmonary haemorrhage), there was one new case of haemoptysis in the second year of PATENT-2 that was fatal and considered study drug-related.19


Conclusions Riociguat is a first-in-class medication, and was approved for the treatment of inoperable CTEPH or persistent PH following pulmonary endarterectomy in 2013. It is the first drug to be approved for this indication. It is important to recognise that pulmonary endarterectomy remains the treatment of choice for CTEPH patients; in patients eligible for surgical intervention, riociguat is not currently indicated. Medical therapy with riociguat should not delay or replace surgical intervention when feasible. In addition, there are no other PAH-specific therapies currently approved for the use in patients with persistent PH following endarterectomy or inoperable CTEPH. Ongoing clinical trials are evaluating the use of riociguat in other types of PH,


including PH associated with lung disease and PH associated with left heart dysfunction (preserved and reduced ejection fraction) has been investigated. Until the results of these clinical trials, riociguat should not be prescribed in these groups of patients. l


References 1. Grimminger F et al. First acute haemodynamic study of soluble guanylate cyclase stimulator riociguat in pulmonary hypertension. Eur Respir J 2009;33:785–92.


2. Ghofrani HA et al. Riociguat for the treatment of chronic thomboembolic pulmonary hypertension. N Engl J Med 2013;369:319–29.


3. Ghofrani HA et al. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med 2013;369:330–40.


4. Hoeper MM et al. Chronic thromboembolic pulmonary hypertension. Lancet Respir Med 2014 [Epub ahead of print].


5. Ribeiro A et al. Pulmonary emboslim: one-year follow-up with echocardiography Doppler and five-year survival analysis. Circulation 1999;99:1325–30.


6. Pengo V et al. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med 2004;350:2257–64.


7. Bonderman D et al. Risk factors for chronic thromboembolic pulmonary hypertension. Eur Respir J 2009;33:325–31.


8. Moser KM, Bloor CM. Pulmonary vascular lesions occurring in patients with chronic major vessel thromboembolic pulmonary hypertension. Chest 1993:103:685–92.


9. Lewczuk J et al. Prognostic factors in medically treated patients with chronic pulmonary embolism. Chest 2001;119:818–23.


10. Lang IM et al. Risk factors and basic mechanisms


of chronic thromboembolic pulmonary hypertension: a current understanding. Eur Respir J 2013;41:462–8.


11. Cannon JE, Pepke-Zaba J. Riociguat for pulmonary hypertension. Expert Rev Clin Pharmacol 2014;7:259–70.


12. Schermuly RT et al. Expression and function of soluble guanylate cyclase in pulmonary arterial hypertension. Eur Respir J 2008;32:881–91.


13. Abe K et al. Formations of plexiform lesions in experimental severe pulmonary arterial hypertension. Circulation 2010;121:2747–54.


14. Ghofrani HA et al. Riociguat for chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension: a phase II study. Eur Respir J 2010;36:792–9.


15. Suntharalingam J et al. Long-term use of sildenafil ininoperable chronic thromboembolic pulmonary hypertension. Chest 2008;134:229–36.


16. Jais X et al. Bosentan for treatment of inoperable chronic thromboembolic pulmonary hypertension:BENEFIT (Bosentan Effects in iNopErable Forms of chronic Thormboembolic pulmonary hypertension); a randomized, placebo-controlled tiral. J Am Coll Cardiol 2008;52:2127–34.


17. Simonneau G et al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension: 2-year results from the CHEST-2 long-term extension. European Respiratory Society International Congress; 6–10 September 2014; Munich, Germany: P1802.


18. Rubin LJ et al. Riociguat for the treatment of pulmonary arterial hypertension (PAH): A Phase III long-term extension study (PATENT-2). ATS 2013; Philadelphia, USA: oral presentation.


19. Rubin LJ et al. Riociguat for the treatment of pulmonary arterial hypertension: 2-year results from the PATENT-2 long-term extension. European Respiratory Society International Congress; 6–10 September 2014; Munich, Germany: P1803.


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Change from baseline in six-minute walk distance (m)


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