Φαρµακοθεραπεία στη Πνευµονική Αρτηριακή Υπέρταση: Αρχική ή διαδοχική συνδυαστική θεραπεία

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1 37 ο Πανελλήνιο Καρδιολογικό Συνέδριο Αθήνα, Οκτώβριος 2016 k Φαρµακοθεραπεία στη Πνευµονική Αρτηριακή Υπέρταση: Αρχική ή διαδοχική συνδυαστική θεραπεία Αναστασία Ανθη Β Κλιν. Εντατικής Θεραπείας & Διακλινικό Ιατρείο Πνευµ. Υπέρτασης Π.Γ.Ν. «ΑΤΤΙΚΟΝ»

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

3 Humbert et al. Circulation. 2014;130:2189-2

4 JACC, June 2009 PAH Evidence-Based Algorithm

5 JACC, June 2009 PAH Evidence-Based Algorithm

6 Goal-oriented use of combination therapy for PAH in 2009 Diagnosis of PAH Vasoreactivity test negative Baseline examination and 3 to 6 monthly re-evaluation to assess treatment goals (Clinically stable, NYHA II, 6-MWD>400m, RAP/CI normal) Treatments goals not met Treatments goals met Start ERA or PDE-5I Continue treatment Add ERA or PDE-5I Continue treatment Parenteral prostanoids and/or enrolment in clinical trials Continue treatment Urgent lung transplantation

7 Recommendations for efficacy of specific therapy for PAH (group 1) according to WHO - FC ESC/ERS guidelines 2009

8 Recommendations for efficacy of specific therapy for PAH (group 1) according to WHO - FC ESC/ERS guidelines 2009

9 PAH: A Progressive Disease of Poor Survival 100 PAH Survival 75 Survival (%) 50 68% 48% 25 34% Years of Followup Adapted from: D Alonzo et al. Ann Internal Med. 1991

10 83% 67% 58% Humbert M et al. Circulation 2010;122: Copyright American Heart Association

11 Hoeper M et al. Lancet RM

12 Hoeper M et al. Lancet RM

13 Hoeper M et al. Lancet RM 2016

14 Hoeper M et al. Lancet RM 2016

15 Seraphin study: Demographics & baseline characteristics N Engl J Med 2013; 369:

16 Patients without the event (%) Seraphin study: Morbidity and mortality up to end of treatment (primary endpoint) Macitentan 10 mg Macitentan 3 mg Placebo Patients at risk Time from treatment start (months) Risk reduction of primary endpoint event vs placebo Macitentan 10 mg: 45% Macitentan 3 mg: 30% Macitentan 10 mg Macitentan 3 mg Placebo Pulido T, et al. N Engl J Med 2013; 369:

17 Seraphin study: Macitentan in combination Morbidity and mortality in pts on background PAH therapy 100 Patients without the event (%) Patients at risk Macitentan 10 mg Macitentan 3 mg Placebo Time from treatment start (months) Risk reduction of primary endpoint event vs placebo Macitentan 10 mg: 38% Macitentan 3 mg: 17% Macitentan 10 mg Macitentan 3 mg Placebo Pulido T, et al. N Engl J Med 2013; 369:

18 Griphon study: Selexipag for the Treatment of PAH Patient demographics: Background PAH medications Total number of patients: ,5% 20,4% None ERA monotherapy PDE-5i monotherapy ERA and PDE-5i in com 14,7% 32,4% Sitbon O, et al. New Engl J Med 2015; 373:

19 Griphon study: Time to first morbidity or mortality event (primary endpoint) 100 Patients without an event (%) Risk reduction 40% selexipag vs placebo Selexipag Placebo Months No. at risk Placebo Selexipag Sitbon O, et al. New Engl J Med 2015; 373:

20 Griphon study: Consistent treatment effect of selexipag on primary composite endpoint according to background therapy Selexipag vs placebo Hazard ratio (99% CI) Selexipag Placebo No. of patients/ no. of events All patients 574/ /242 PAH specific therapy at baseline (interaction ERA + PDE-5i p value = 0.95) 179/47 197/80 ERA monotherapy 94/23 76/29 PDE-5i monotherapy 189/54 185/84 No PAH-specific therapy 112/31 124/49 Favours selexipag Favours placebo Sitbon O, et al. N Engl J Med 2015;373:

21 Ambition study NEJM August 27, 2015

22 Ambition study: upfront combination therapy with ambrisentan/ tadalafil reduced the risk of morbidity/mortality 50% Risk Reduction N. Galiè, et al. N Engl J Med 2015;373:834-44

23 N. Galiè, et al. N Engl J Med 2015;373: Ambition study: upfront combination therapy with ambrisentan/ tadalafil CONFIDENTIAL

24 Patent-1 study: Riociguat for the Treatment of PAH N Engl J Med 2013;369:330-40

25 Patent-1 study: Riociguat for the Treatment of PAH N Engl J Med 2013;369:330-40

26 Patent-2 study: long-term extension trial Lancet R M 2016; 4:

27 Evidence based treatment algorithm for PAH patients PH guidelines

28 Evidence based treatment algorithm for PAH patients PH guidelines

29 Risk assessment in pulmonary arterial hypertension guidelines 2015 PH

30 Risk assessment in pulmonary arterial hypertension Achievement/maintenance of an intermediate-risk profile should be considered an inadequate treatment response for most patients with PAH guidelines 2015 PH

31 Risk assessment in pulmonary arterial hypertension Achievement/maintenance of an intermediate-risk profile should be considered an inadequate treatment response for most patients with PAH Achievement/maintenance of a low-risk profile is recommended as an adequate treatment response for patients with PAH guidelines 2015 PH

32 Risk assessment in pulmonary arterial hypertension guidelines 2015 PH

33 Evidence based treatment algorithm for PAH patients PH guidelines

34 Evidence based treatment algorithm for PAH patients Initial monotherapy PH guidelines

35 Evidence based treatment algorithm for PAH patients Initial oral combination PH guidelines

36 Evidence based treatment algorithm for PAH patients Initial Combination therapy including iv PCA PH guidelines

37 Recommendations for efficacy of initial drug combination therapy for PAH (group 1) according to WHO FC PH guidelines 2015

38 Recommendations for efficacy of sequential drug combination therapy for PAH (group 1) according to WHO FC PH

39 Evidence based treatment algorithm for PAH patients PH guidelines

40 Upfront triple combination therapy in pulmonary arterial hypertension: a pilot study 1697 Sitbon O. et al. Eur Respir J 2014; 43: 1691

41 Initial dual oral combination therapy in PAH Eur Respir J 2016; 47:

42 Initial dual oral combination therapy in PAH Eur Respir J 2016; 47:

43 Initial dual oral combination therapy in PAH Eur Respir J 2016; 47: