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Pulmonary hypertension Goal directed therapy

Pulmonary hypertension Goal directed therapy

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Pulmonary hypertension Goal directed therapy

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  1. Pulmonary hypertensionGoal directed therapy Pulmonary Hypertension Programme University of Toronto FMD

  2. Disclaimer (1999) • Support from • No one in particular

  3. Disclaimer (2011) • Support from • Actelion • Glaxo • Pfizer • United Therapeutics / Northern Therapeutics • Gilead • Lilly • Bayer

  4. Goals • Identify modifiable and non-modifiable prognostic factors in patients with pulmonary arterial hypertension • Interpret changes in hemodynamics and other indicators of disease severity • Recognize how therapy is targeted in patients with pulmonary hypertension

  5. Dana Point Classification of PH Galiè N et al. Eur Heart J 2009; 30:2493-537 Galiè N et al. Eur Resp J 2009; 34:1219-63

  6. Caregiver burden • Emergent themes were • stresses on physical and mental well-being, • Stress on social and personal lives, • Threats to financial security and career paths. • The interviewees reported a sense of isolation as related to dealing with a disease that is relatively unknown to the majority of friends and family.

  7. “The unwillingness to admit to their loved-ones, or indeed to themselves, that the caregiver role was taxing, augmented the sense of isolation”

  8. An imbalance... Vasoconstrictors Vasodilators

  9. What is it?

  10. Echo measures of RV function TAPSE Tei Index = (a – b) / b Eccentricity index

  11. Goals of treatment • Improve quality of life • Restore exercise capacity • Improve survival

  12. Treatment paradigm • Add therapy for disease progression

  13. Dead Off bosentan On dual agents On bosentan alone % of patients (n=169) 12 months 24 months 2005; 25: 244–249

  14. Treatment paradigm • Add therapy for disease progression • Add therapy for failure to reach goals

  15. Respiratory Medicine (2010) 104, 1588e1607

  16. Respiratory Medicine (2010) 104, 1588e1607

  17. Impact of Functional Class on Survival Functional Class at Baseline Functional Class at 17±15 mos 100 100 80 80 FC=1 60 60 Survival (%) FC=3 Survival (%) FC=2 40 40 20 20 FC=3 FC=4 p=0.0001 by log-rank test FC=4 0 0 84 0 12 24 36 48 60 72 84 0 12 24 36 48 60 72 115 112 86 63 46 30 20 10 No. at risk 162 33 95 70 48 30 20 10 No. at risk: Months Months McLaughlin VV, et al. Circulation. 2002;106:1477-1482.

  18. JACC Vol. 40, No. 4, 2002

  19. Circulation. 2006;114:1482-1489

  20. Multivariate predictors of 1 year outcome in REVEAL Predicting survival in pulmonary arterial hypertension: insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL). Benza RL; Miller DP; Gomberg-Maitland M; Frantz RP; Foreman AJ; Coffey CS; Frost A; Barst RJ; Badesch DB; Elliott CG; Liou TG; McGoon MD Figure 2. Cox proportional-hazards estimates for multivariable model of survival, limited to terms included in the final stepwise model. Parameters significantly associated with 1-year survival only in univariable analyses included the Borg dyspnea scale, right ventricular dysfunction, pulmonary vascular resistance (PVR) index, pulmonary capillary wedge pressure, cardiac index, mean pulmonary artery pressure, and total serum bilirubin. Candidate predictor variables that were not significant at the univariable level included Tei index, vasoreactivity, race, newly diagnosed PAH, and income. Missing Borg scale and missing PVR index were both associated with lower-than-average observed survival and were therefore considered candidate predictor variables. APAH indicates associated I PAH; ECHO, echocardiogram; FPAH, familial PAH; mRAP, mean right atrial pressure; PoPH, portopulmonary hypertension; and RHC, right heart catheterization. *Reference category: NYHA/WHO functional class (Fn) II or missing. +If N-terminal proBNP is available and BNP is not, listed cut points are replaced with 1500 pg/mL. ++Restricted to tests performed within 1 year of enrollment; otherwise, the indicator is set to 0. Circulation. 122(2):164-72, 2010 Jul 13. 2

  21. REVEAL observed 1-year survival from time of enrollment according to predicted risk strata. Risk 1 yr survival Low > 95% Average 90-95% Mod high 85-90% High risk 70-85% Very high risk <70%

  22. 15 possible risk factors 4 possible protective factors 0 - 22 Actual scores ranged from 1 – 15 With a mean of 7.4

  23. Prevalent cases Incident cases

  24. Combination therapy • 26 observational studies and 5 randomized trials were identified. • PDE-5 inhibitor and prostanoids,6/7 studies reported improvement in 6MWD, 6/8 studies reported improvement in functional class, 6/6 studies reported improvement in hemodynamics and 1/2 trials demonstrated improvement in quality of life and time-to-clinical worsening. • ERA and prostanoids, 4/6 studies and 1 trial reported improvement in 6MWD, 3/3 studies and 1/4 trials reported improvement in functional class, 4/5 studies and 1/4 trials reported improvement in PAP. • ERA and PDE-5 inhibitor, 4/7 studies reported an improvement in 6MWD, and 2/6 studies report improvement in functional class.

  25. Galiè N et al. Eur Heart J 2009; 30:2493-537 Galiè N et al. Eur Resp J 2009; 34:1219-63

  26. Galiè N et al. Eur Heart J 2009; 30:2493-537 Galiè N et al. Eur Resp J 2009; 34:1219-63

  27. Prognosticallyimportant variablesandtreatmentgoals

  28. CHEST 2006; 130:214–217

  29. IIt’s best to avoid standing directly between a competitive jerk and his goals