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CTEPH: treatment


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;2(7):573–82.


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.


overall population, NT-proBNP changed by 416±1321pg/ml versus baseline. At one year, WHO FC had improved/ stabilised/worsened in 50/45/4%, respectively, of patients in the former riociguat group, 39/59/2% of patients in the former placebo group and 47/50/3% of patients in the overall population. The proportion of patients in the overall population in WHO FC I/II/III/IV at one year was 14/54/31/1%, respectively, compared with 1/31/65/3% at baseline. At the end of CHEST-1, mean±SD 6MWD had increased from CHEST-1 baseline by +50±59m in riociguat patients versus +8±63m in placebo patients. At two years in CHEST-2, the increase was +50±68m (n=162). At the end of CHEST-1 WHO FC improved/ stabilised/worsened in 35/62/3% of riociguat patients versus 16/81/2% of placebo patients; proportions were 39/58/3% at two years. At two years, survival was 93% and 15 patients (10%) were receiving additional PAH therapy.18


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Safety and tolerability The safety profile of riociguat in CHEST-2 was similar to CHEST-1, with no new safety signals. The most drug- related adverse events (AEs) were dizziness (11%), dyspepsia (8%) and hypotension (5%). There were seven (3%) drug-related syncope serious AEs; four (2%) pulmonary bleeding serious AEs were not drug-related. With respect to safety and tolerability, in CHEST-2, three cases of haemoptysis were reported


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at years one and two (one mild, one moderate and one severe). No cases were considered to be study drug-related.18


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 and only 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 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.


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: a long-term extension study (CHEST-2). Eur Resp J 2015;45(5):1293–302.


18. 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.


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