Riociguat for the treatment of pulmonary hypertension: Chinese subgroup analyses and comparison

Chen Wang, Zhi-Cheng Jing, Yi-Gao Huang, Da-Xin Zhou, Zhi-Hong Liu, Christian Meier, Sylvia Nikkho, John Curram, Peng Zhang, Jian-Guo He, Chen Wang, Zhi-Cheng Jing, Yi-Gao Huang, Da-Xin Zhou, Zhi-Hong Liu, Christian Meier, Sylvia Nikkho, John Curram, Peng Zhang, Jian-Guo He

Abstract

Objective: PATENT-1 and CHEST-1 were pivotal, international phase III trials assessing riociguat for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Here we compare Chinese patients from these studies with the overall populations, and report the clinical effect and safety of riociguat in Chinese patients with PAH and CTEPH.

Methods: PATENT-1 was a 12-week, randomised, double-blind, placebo-controlled trial of riociguat (maximum 2.5 mg three times daily or 1.5 mg three times daily (exploratory) in patients with PAH. CHEST-1 was a 16-week, randomised, double-blind, placebo-controlled trial of riociguat (maximum 2.5 mg three times daily) in patients with inoperable CTEPH or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy. The primary endpoint in each study was change from baseline to study end in 6 min walking distance (6MWD). Secondary endpoints included pulmonary vascular resistance (PVR), N-terminal prohormone of brain natriuretic peptide, WHO functional class (FC), and time to clinical worsening.

Results: Chinese patients in PATENT-1 (n=77) and CHEST-1 (n=32) were younger and had better baseline 6MWD and WHO FC versus the overall population. Riociguat increased 6MWD versus placebo in Chinese patients in PATENT-1 and CHEST-1, with a greater increase observed in CHEST-1 (least-squares mean differences +46 m and +102 m in PATENT-1 and CHEST-1, respectively). Riociguat also improved several secondary endpoints in both studies, and was well tolerated.

Conclusions: Chinese patients displayed differences in baseline characteristics versus the overall populations in PATENT-1 and CHEST-1. Riociguat improved 6MWD, PVR, WHO FC, and other clinical outcomes in Chinese patients with PAH or CTEPH.

Trial registration number: PATENT-1: NCT00810693, Results; CHEST-1 NCT00855465, Results.

Figures

Figure 1
Figure 1
Disposition of Chinese patients in PATENT-1 (A) and CHEST-1 (B). CTEPH, chronic thromboembolic pulmonary hypertension; PAH, pulmonary arterial hypertension.
Figure 2
Figure 2
Mean change from baseline in 6MWD in (A) Chinese patients with PAH in PATENT-1 and (B) Chinese patients with CTEPH in CHEST-1. Mean (±SEM) changes from baseline in 6MWD are shown for the modified intention-to-treat Chinese population without imputation of missing values, with the imputed values also provided at week 12 (PATENT-1) and week 16 (CHEST-1). The number of patients at each time point is indicated below the graph. Missing data were imputed at week 12/16 according to the last observation carried forward, except in cases of death or clinical worsening without a termination visit, where the worst value (0 m) was imputed. 6MWD, 6 min walking distance; CTEPH, chronic thromboembolic pulmonary hypertension; PAH, pulmonary arterial hypertension.

References

    1. Galiè 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). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J 2016;37:67–119.
    1. Schermuly RT, Ghofrani HA, Wilkins MR et al. . Mechanisms of disease: pulmonary arterial hypertension. Nat Rev Cardiol 2011;8:443–55.
    1. Kim NH, Delcroix M, Jenkins DP et al. . Chronic thromboembolic pulmonary hypertension. J Am Coll Cardiol 2013;62:D92–9.
    1. O'Connell C, O'Callaghan DS, Humbert M. Novel medical therapies for pulmonary arterial hypertension. Clin Chest Med 2013;34:867–80.
    1. Benza RL, Miller DP, Barst RJ et al. . An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry. Chest 2012;142:448–56.
    1. Zhang R, Dai LZ, Xie WP et al. . Survival of Chinese patients with pulmonary arterial hypertension in the modern treatment era. Chest 2011;140:301–9.
    1. Zhai Z, Wang J, Zhao L et al. . Pulmonary hypertension in China: pulmonary vascular disease: the global perspective. Chest 2010;137:69S–77S.
    1. Gu S, Liu Y, Su PX et al. . Pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension: preliminary exploration in China. Chin Med J 2010;123:979–83.
    1. Humbert M. Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: pathophysiology. Eur Respir Rev 2010;19:59–63.
    1. Ghofrani HA, Galiè N, Grimminger F et al. . Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med 2013;369:330–40.
    1. Ghofrani HA, D'Armini AM, Grimminger F et al. . Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med 2013;369:319–29.
    1. McGoon MD, Benza RL, Escribano-Subias P et al. . Pulmonary arterial hypertension: epidemiology and registries. J Am Coll Cardiol 2013;62:D51–9.
    1. Dong L, He JG, Liu ZH et al. . [Multicenter study of disease attributes in adult patients with pulmonary hypertension]. Zhonghua Yi Xue Za Zhi 2012;92:1087–90.
    1. Simonneau G, Barst RJ, Galiè N 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;165:800–4.
    1. Galiè N, Ghofrani HA, Torbicki A et al. . Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 2005;353:2148–57.
    1. Galiè N, Brundage BH, Ghofrani HA et al. . Tadalafil therapy for pulmonary arterial hypertension. Circulation 2009;119:2894–903.
    1. Olschewski H, Simonneau G, Galiè N et al. . Inhaled iloprost for severe pulmonary hypertension. N Engl J Med 2002;347:322–9.
    1. Galie N, Olschewski H, Oudiz RJ et al. . Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2. Circulation 2008;117:3010–19.
    1. Rubin LJ, Badesch DB, Barst RJ et al. . Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 2002;346:896–903.
    1. Dai LZ, Jiang X, Wang Y et al. . [The efficacy and safety of bosentan therapy for Chinese patients with idiopathic pulmonary arterial hypertension: an open-label, prospective multicenter study]. Zhonghua Xin Xue Guan Bing Za Zhi 2011;39:124–7.
    1. Zeng WJ, Xiong CM, Zhao L et al. . Atorvastatin in pulmonary arterial hypertension (APATH) study. Eur Respir J 2012;40:67–74.
    1. Chen FD, Zhou DX, Di RM et al. . [Efficacy and safety of ambrisentan therapy in Chinese patients with pulmonary hypertension]. Zhonghua Yi Xue Za Zhi 2013;93:2736–8.
    1. Xiong CM, Lu XL, Shan GL et al. . Oral sildenafil therapy for Chinese patients with pulmonary arterial hypertension: a multicenter study. J Clin Pharmacol 2012;52:425–31.
    1. Xu XQ, Jing ZC, Zhang JH et al. . The efficacy and safety of sildenafil in Chinese patients with pulmonary arterial hypertension. Hypertens Res 2009;32:911–15.
    1. Jing ZC, Strange G, Zhu XY et al. . Efficacy, safety and tolerability of bosentan in Chinese patients with pulmonary arterial hypertension. J Heart Lung Transplant 2010;29:150–6.
    1. Gabler NB, French B, Strom BL et al. . Validation of 6-minute walk distance as a surrogate end point in pulmonary arterial hypertension trials. Circulation 2012;126:349–56.
    1. Mathai SC, Puhan MA, Lam D et al. . The minimal important difference in the 6-minute walk test for patients with pulmonary arterial hypertension. Am J Respir Crit Care Med 2012;186:428–33.
    1. Jaïs X, D'Armini AM, Jansa P 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;52:2127–34.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner