1. Exploring Early Combination Therapy in PAH

3. Program Overview

4. Assessing Risk of Disease Progression in PAH

5. A Multi-Parameter Risk Assessment Is Needed

6. Comprehensive Prognostic Evaluation and Risk Assessment

7. Risk Assessment in PAH

8. Risk Assessment Is Fundamental for Determining an Optimal Treatment Strategy

9. Case Example: 25-Year-Old Woman With Heritable PAH*

10. 2015 ESC/ERS Guidelines: Risk Stratification in PAH

11. Mortality in PAH: Prediction by the 2015 European PH Guidelines Risk Stratification Model

12. PAH Risk Assessment and Survival in COMPERA

13. PAH Risk Assessment and Survival in COMPERA

14. Risk Assessment, Prognosis, and Guideline Implementation in PAH

15. Risk Assessment and Survival: The French Registry

16. Variables Associated With a Higher Risk of Death or Transplantation

17. Variables Associated With a Higher Risk of Death or Transplantation (cont)

18. Risk Assessment and Survival: The French Registry (cont)

19. 2015 ESC/ERS Guidelines: Goal of Therapy

20. Using the Risk Stratification Table From the ESC/ERS PH Guidelines: Practical Recommendations

21. Patient Risk: NYHA FC I/II Is Still Advanced Disease

22. Patient Risk: NYHA FC Is Still Advanced Disease (cont)

23. AMBITION: Disease Severity at Baseline*

24. AMBITION*: Significant Improvement in Outcomes With Initial Ambrisentan + Tadalafil

25. AMBITION: Initial Combination Therapy in Patients With FC II or III PAH

26. 24-Year-Old "Asymptomatic" BMPR 2 Mutation Carrier Diagnosed With PAH During Screening

27. 24-Year-Old "Asymptomatic" BMPR 2 Mutation Carrier Diagnosed With PAH During Screening (cont)

28. 24-Year-Old "Asymptomatic" BMPR 2 Mutation Carrier Diagnosed With PAH During Screening (cont)

29. PAH Progresses Rapidly in Patients on Monotherapy

30. AMBITION: First Adjudicated Clinical Failure by Subgroup

31. 2015 ESC/ERS Guidelines: Combination Therapy Is Widely Recommended and Supported by Clinical Trial Data

32. Hemodynamic Effects of Different Types of Initial Oral Combination Therapy in PAH

33. Ambrisentan + Tadalafil: Improved Outcomes With Initial Combination Therapy vs Monotherapy*

34. Bosentan + Tadalafil: Improved Outcomes With Initial Combination Therapy vs Monotherapy*

35. Initial Dual Oral Combination Therapy: All Regimens Were Associated With Improved HDs

36. OPTIMA*: Combination Therapy With Macitentan and Tadalafil Led to Improvements in HDs and FC

37. Summary: Treatment Recommendations

38. Residual Role of Monotherapy in a Minority of PAH Subsets

39. Potential Barriers to Starting Initial Combination Therapy

40. AMBITION: AEs Leading to Treatment Discontinuation

41. Potential Barriers to Starting Initial Combination Therapy (cont)

42. Potential Barriers to Starting Initial Combination Therapy (cont)

43. Potential Barriers to Starting Initial Combination Therapy (cont)

44. Potential Barriers to Starting Initial Combination Therapy (cont)

45. Common AEs of Initial Combination Therapy

46. Managing Potential AEs

47. Conclusions

48. Abbreviations

49. Abbreviations (cont)

50. Abbreviations (cont)

51. Abbreviations (cont)