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CTEPH: medical treatment


messenger cGMP.


Riociguat has a dual mode of action: it increases the sensitivity of sGC to endogenous bioavailable nitric oxide (NO) by stabilising the NO-sGC binding and stimulates directly sGC


independently of NO. Oral administration of riociguat results in an increase of cGMP with antifibrotic (vascular remodelling) and vasodilating effects. The most recent and largest RCT of medical treatment in CTEPH to date is the CHEST-1 (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial-1), including 261 patients of whom 27% had post-operative residual or persistent PH after PEA.20


Patients were randomised to


receive either placebo or riociguat and were studied for 16 weeks. The six minute walk distance increased from baseline by a mean of 39m in the riociguat group (95% confidence interval: 25 to 67; p<0.001). PVR decreased by 226 dyn.sec. cm-5 in the riociguat group (95% confidence interval: –303 to –190; p<0.001). Riociguat therapy was also associated with significant improvements in NT-proBNP level (p<0.001) and WHO functional class (p=0.003). This study became the first to show significant clinical efficacy in CTEPH and was pivotal for the approval by the US Food and Drug Administration and by the European Medical Agency for the treatment of patients with inoperable or persistent/ recurrent pulmonary hypertension after PEA.


Other treatment options In select inoperable cases, or after PEA failure, lung transplantation could be considered.


Balloon pulmonary angioplasty, a technique developed in Japan, could become a potential promising alternative for inoperable patients but needs further validation.21


(Figure 1) Conclusions


Once CTEPH is diagnosed, all patients should receive life-long anticoagulation therapy unless contra-indicated. The standard and potentially curative treatment for CTEPH is PEA, a surgical procedure in which the pulmonary blood vessels are cleared of obstructive material. Therefore all CTEPH patients should be evaluated for operability by an experienced CTEPH team.


34


If a patient is considered inoperable by an experienced CTEPH team, a second


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“Riociguat is the first, and so far only, drug to demonstrate significant clinical efficacy in patients with inoperable CTEPH or persistent/ recurrent CTEPH after pulmonary endarterectomy and has been approved by the EMA and FDA”


In select cases lung transplantation could be considered. Balloon pulmonary angioplasty, a technique developed in Japan, could become a potential promising alternative but further studies are required.21 l


References 1. Pepke-Zaba J et al. Chronic thromboembolic pulmonary hypertension (CTEPH): results from an international prospective registry. Circulation 2011;124(18):1973–81.


2. Mayer E et al. Surgical management and outcome of patients with chronic thromboembolic pulmonary hypertension: results from an international prospective registry. J Thorac Cardiovasc Surg 2011;141(3):702–10.


3. Kim NH et al. Chronic thromboembolic pulmonary hypertension. J Am Coll Cardiol 2013;62(25 Suppl):D92–D99.


4. Langer F et al. Circulating big endothelin-1: an active role in pulmonary thromboendarterectomy? J Thorac Cardiovasc Surg 2005;130(5):1342–7.


5. Moser KM, Bloor CM. Pulmonary vascular lesions occurring in patients with chronic major vessel thromboembolic pulmonary hypertension. Chest 1993;103(3):685–92.


6. Reesink HJ et al. Hemodynamic and clinical correlates of endothelin-1 in chronic thromboembolic pulmonary hypertension. Circ J 2006;70(8):1058–63.


7. Riedel M et al. Longterm follow-up of patients with pulmonary thromboembolism. Late prognosis and evolution of hemodynamic and respiratory data. Chest 1982;81(2):151–8.


12. Olschewski H et al. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med 2002;347(5):322–9.


13. Galie N et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 2005;353(20):2148–57.


14. Reichenberger F et al. Long-term treatment with sildenafil in chronic thromboembolic pulmonary hypertension. Eur Respir J 2007;30(5):922–7.


15. Suntharalingam J et al. Long-term use of sildenafil in inoperable chronic thromboembolic pulmonary hypertension. Chest 2008;134(2):229–36.


16. Rubin LJ et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 2002;346(12):896–903.


17. Jais X et al. Bosentan for treatment of inoperable chronic thromboembolic pulmonary hypertension: BENEFiT (Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension), a randomized, placebo-controlled trial. J Am Coll Cardiol 2008;52(25):2127–34.


18. Mittendorf J et al. Discovery of riociguat (BAY 63-2521): a potent, oral stimulator of soluble guanylate cyclase for the treatment of pulmonary hypertension. Chem Med Chem 2009;4(5):853–65.


19. Schermuly RT et al. Riociguat for the treatment of pulmonary hypertension. Expert Opin Investig Drugs 2011;20(4):567–76.


20. Ghofrani HA et al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med 2013;369(4):319–29.


21. Mizoguchi H et al. Refined balloon pulmonary angioplasty for inoperable patients with chronic thromboembolic pulmonary hypertension. Circ Cardiovasc Interv 2012;5(6):748–55.


opinion is recommended.


For inoperable patients, or patients with persistent pulmonary hypertension after pulmonary endarterectomy, medical treatment is recommended. Several open-label and randomised controlled trials of three to six months duration have reported different degrees of efficacy with medical treatment. Riociguat is the first and so far only drug to demonstrate significant clinical efficacy in patients with inoperable CTEPH or persistent/ recurrent CTEPH after pulmonary endarterectomy and has been recently approved by the American Food and Drug Administration and European Medical Agency.


8. Rubin LJ et al. Prostacyclin-induced acute pulmonary vasodilation in primary pulmonary hypertension. Circulation 1982;66(2):334–8.


9. Cabrol S et al. Intravenous epoprostenol in inoperable chronic thromboembolic pulmonary hypertension. J Heart Lung Transplant 2007;26(4):357–62.


10. Simonneau G et al. Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med 2002;165(6): 800–4.


11. Skoro-Sajer N et al. Treprostinil for severe inoperable chronic thromboembolic pulmonary hypertension. J Thromb Haemost 2007;5(3): 483–9.


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