Διέγερση της sgc στη κλινική πράξη: Περιστατικό Πνευμονικής Αρτηριακής Υπέρτασης Αναστασία Ανθη Β Κλινική Εντατικής Θεραπείας & Ιατρείο Πνευμονικής Υπέρτασης Π.Γ.Ν. «ΑΤΤΙΚΟΝ»
Disclosures Sponsored to attend scientific meetings, or honoraria by: Actelion Bayer Galenica GSK MSD Pfizer
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)
Echocardiography LV : EF 65 % RV: διάταση & διάχυτη υποκινησία TRV: 3,9 m/s
Echocardiography LV : EF 65 % RV: διάταση & διάχυτη υποκινησία TRV: 3,9 m/s
Echocardiography LV : EF 65 % RV: διάταση & διάχυτη υποκινησία TRV: 3,9 m/s
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
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
Clinical classification of Pulmonary Hypertension (ESC/ERS guidelines 2015)
ESC/ERS PH guidelines 2015
Risk assessment in pulmonary arterial hypertension ESC/ERS PH guidelines 2015
Risk assessment in pulmonary arterial hypertension ESC/ERS PH guidelines 2015
Evidence based treatment algorithm for PAH patients PH guidelines 2015
Riociguat sgc stimulator enhances cgmp production is potentially effective also in conditions in which endogenous NO is depleted
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
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
PATENT-1 study N Engl J Med 2013;369:330-40.
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
WHO FC Eur Respir J 2015; 45: 1303 1313
WHO FC Eur Respir J 2015; 45: 1303 1313
PATENT-1: PAH-CTD subgrouping PAH-CTD patients were further analyzed in 3 subgroups (SSc, CTD other than SSc and unspecified CTD)
Patent-1: Baseline parameters and demographics of PAH-CTD patients
PATENT-1: Effect of riociguat on WHO FC by PAH-CTD subgroup at week 12
PATENT-1: Effect of riociguat on hemodynamic endpoints in the overall PAH-CTD population
PATENT-2: Efficacy in 6MWD was maintained over 2 years in patients with PAH-CTD receiving riociguat
Baseline 12 weeks Right Heart Catheterization RAP 9 11 mmhg PAP 59/26/37 62/26/38 mmhg (S/D/M) PAWP 11 13 mmhg CO 4 4,4 l/min CI 2,5 2,8 l/min/m 2 PVR 6,5 5,6 Wood Units SvO2 68 75 % 6MWT: 387 430 m WHO class: ΙΙI late III early NT-proBNP: 205 196 pg/ml
Change in 6-min walking distance (6MWD) from baseline to 2 years Baseline 12 12 6 9 1 15 18 21 2 weeks weeks months months year months months months years PATENT - 1 PATENT - 2
Update in systemic sclerosis-associated PAH M. Gashouta, M. Humbert, P. Hassoun. Presse Med. 2014
Recommendations for pulmonary arterial hypertension screening ESC/ERS PH guidelines 2015
Survival rate (%) Screening improves long-term outcomes in SSc patients 100 90 100% 81% 73% p = 0.0037 HR = 4.15 (95% CI 1.47-11.71) 80 70 60 50 40 30 20 10 75% 31% 25% 64% 17% Screened PAH-SSc (n = 16) Routine practice PAH-SSc (n = 16) 0 34; 20 March 2016 1 year 3 years 5 years 8 years Follow-up (years) Humbert M, et al. Arthritis Rheum 2011; 63:3522-30.
Cumulative survival from date of diagnosis for common diagnostic subgroups of PH Hurdman J et al. Eur Respir J 2012; 39: 945 955
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):448 456
Lancet Respir Med, May 2016; 4: 361 71
Lancet Respir Med, May 2016; 4: 361 71
Lancet Respir Med, May 2016; 4: 361 71
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: 361 71