Διέγερση της sgc στη κλινική πράξη: Περιστατικό Πνευμονικής Αρτηριακής Υπέρτασης

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1 Διέγερση της sgc στη κλινική πράξη: Περιστατικό Πνευμονικής Αρτηριακής Υπέρτασης Αναστασία Ανθη Β Κλινική Εντατικής Θεραπείας & Ιατρείο Πνευμονικής Υπέρτασης Π.Γ.Ν. «ΑΤΤΙΚΟΝ»

2 Disclosures Sponsored to attend scientific meetings, or honoraria by: Actelion Bayer Galenica GSK MSD Pfizer

3 Γυναίκα, 72 ετών Ατομικό αναμνηστικό: Αρτηριακή υπέρταση Δυσλιπιδαιμία Χολοκυστεκτομή Θυρεοειδεκτομή Εκκολπώματα παχέος εντέρου Φ. Raynaud από νεαρή ηλικία Διάγνωση σκληροδέρματος (από τριετίας) Aγωγή : Aprovel 150mg x 1 T4 137 mcg x 1 Lipitor 10 mg x 1 Amprisentan 5 mg x 1 (από τριετίας)

4 Echocardiography LV : EF 65 % RV: διάταση & διάχυτη υποκινησία TRV: 3,9 m/s

5 Echocardiography LV : EF 65 % RV: διάταση & διάχυτη υποκινησία TRV: 3,9 m/s

6 Echocardiography LV : EF 65 % RV: διάταση & διάχυτη υποκινησία TRV: 3,9 m/s

7 PFT s FVC 102 % pred. FEV1 90 % pred. FEV1/FVC 70 TLC 74 % pred. DLCO 32 % pred. Lung perfusion scan: αρνητικό για PE HRCT/CTA: διάταση πνευμ. αρτηρίας, δεξιών καρδ. Κοιλοτήτων Αιματολογικός, βιοχημικός ελεγχος: χωρίς ιδιαίτερα ευρήματα Ανοσολογικός ελεγχος: συμβατός με νόσο του συνδετικού ιστού

8 Baseline Right Heart Catheterization RAP 9 mmhg PAP 59/26/37 mmhg (S/D/M) PAWP 11 mmhg CO 4 l/min CI 2,5 l/min/m 2 PVR 6,5 Wood Units SvO2 68 % 6MWT: 387 m WHO class: ΙΙI late NT-proBNP: 205 pg/ml

9 Clinical classification of Pulmonary Hypertension (ESC/ERS guidelines 2015)

10 ESC/ERS PH guidelines 2015

11 Risk assessment in pulmonary arterial hypertension ESC/ERS PH guidelines 2015

12 Risk assessment in pulmonary arterial hypertension ESC/ERS PH guidelines 2015

13 Evidence based treatment algorithm for PAH patients PH guidelines 2015

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16 Riociguat sgc stimulator enhances cgmp production is potentially effective also in conditions in which endogenous NO is depleted

17 Riociguat sensitizes sgc to endogenous NO by stabilizing the NO sgc binding cgmp GTP sgc cgmp GTP sgc cgmp cgmp GTP cgmp GTP cgmp GTP cgmp GTP cgmp Stasch et al. Nature 2001;410:212 15; Evgenov et al. Nature Rev Drug Discov 2006;5:755 68; Stasch and Evgenov. Handb Exp Pharmacol 2013;218:279 31

18 Riociguat directly stimulates sgc via a different binding site, independently of NO GTP sgc GTP sgc cgmp cgmp GTP cgmp GTP cgmp GTP GTP Stasch et al. Nature 2001;410:212 15; Evgenov et al. Nature Rev Drug Discov 2006;5:755 68; Stasch and Evgenov. Handb Exp Pharmacol 2013;218:279 31

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20 PATENT-1 study N Engl J Med 2013;369:

21 Riociguat significantly improved the 6-MWD, PVR and several other secondary efficacy end points in patients with symptomatic PAH who were receiving no other treatment for the disease or ERAs or prostanoids

22 WHO FC Eur Respir J 2015; 45:

23 WHO FC Eur Respir J 2015; 45:

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25 PATENT-1: PAH-CTD subgrouping PAH-CTD patients were further analyzed in 3 subgroups (SSc, CTD other than SSc and unspecified CTD)

26 Patent-1: Baseline parameters and demographics of PAH-CTD patients

27 PATENT-1: Effect of riociguat on WHO FC by PAH-CTD subgroup at week 12

28 PATENT-1: Effect of riociguat on hemodynamic endpoints in the overall PAH-CTD population

29 PATENT-2: Efficacy in 6MWD was maintained over 2 years in patients with PAH-CTD receiving riociguat

30 Baseline 12 weeks Right Heart Catheterization RAP 9 11 mmhg PAP 59/26/37 62/26/38 mmhg (S/D/M) PAWP mmhg CO 4 4,4 l/min CI 2,5 2,8 l/min/m 2 PVR 6,5 5,6 Wood Units SvO % 6MWT: m WHO class: ΙΙI late III early NT-proBNP: pg/ml

31 Change in 6-min walking distance (6MWD) from baseline to 2 years Baseline weeks weeks months months year months months months years PATENT - 1 PATENT - 2

32 Update in systemic sclerosis-associated PAH M. Gashouta, M. Humbert, P. Hassoun. Presse Med. 2014

33 Recommendations for pulmonary arterial hypertension screening ESC/ERS PH guidelines 2015

34 Survival rate (%) Screening improves long-term outcomes in SSc patients % 81% 73% p = HR = 4.15 (95% CI ) % 31% 25% 64% 17% Screened PAH-SSc (n = 16) Routine practice PAH-SSc (n = 16) 0 34; 20 March year 3 years 5 years 8 years Follow-up (years) Humbert M, et al. Arthritis Rheum 2011; 63:

35 Cumulative survival from date of diagnosis for common diagnostic subgroups of PH Hurdman J et al. Eur Respir J 2012; 39:

36 An Evaluation of Long-term Survival From Time of Diagnosis in Pulmonary Arterial Hypertension From the REVEAL Registry Benza RL et al. CHEST 2012; 142(2):

37 Lancet Respir Med, May 2016; 4:

38 Lancet Respir Med, May 2016; 4:

39 Lancet Respir Med, May 2016; 4:

40 These results support the long-term use of riociguat in patients with pulmonary arterial hypertension, and emphasise the prognostic value of 6MWD, WHO functional class, and NT-proBNP concentrations. Lancet Respir Med, May 2016; 4: