Management of Pulmonary Arterial Hypertension: Evolution in Management

Transcription

1 Management of Pulmonary Arterial Hypertension: Evolution in Management Stephen C. Mathai, MD MHS The Johns Hopkins Pulmonary Hypertension Program Assistant Professor of Medicine Johns Hopkins University

2 Disclosures Grant monies: Na2onal Ins2tutes of Health/ NHLBI Pulmonary Hypertension Associa2on Consultant fee: Bayer HealthCare, Actelion

3 Learning Objec-ves Medical Therapies in PAH: What do the WHO Proceedings and CHEST Guidelines Tell Us? Define the World Health Organiza-on (WHO) Classifica-ons of pulmonary hypertension Iden-fy the necessary steps to appropriately diagnose pa-ents with PAH earlier in the course of the disease Iden-fy the pharmacologic therapies in PAH

4 Pre- Test Ques-ons Q 1. The Federal Drug Administra-on (FDA) has approved therapies for which of the following forms of pulmonary hypertension? 1. Pulmonary arterial hypertension 2. Pulmonary hypertension (PH) related to let heart disease 3. Chronic thromboembolic pulmonary hypertension 4. 1 and 3

5 Pre- Test Ques-ons Q 2. Selec-on of ini-al therapy for PAH should be based upon which of the following? NYHA/WHO func-onal class Mean pulmonary artery pressure 6MW distance How recently the agent was FDA approved

6 Case Presenta-on 45 year old female SLE diagnosed 4 years ago SLE complicated by severe Raynaud s dz Mul-ple digital ulcers treated with nifidipine Admi^ed 2 weeks ago for purple toe, dx= threatened digit loss Treated with alprostadil, nitrates

7 Case Presenta-on (con-nued) Diagnoses: Severe pulmonary hypertension, WHO Group 1 NYHA/WHO FC II (early) No RHF/preserved CO/normal RV on echo Pericardial effusion, probably SLE- related Severe Raynaud s disease SLE

8 Case Presenta-on (con-nued) Ini-ated PAH- specific therapy NO- ac-ve drugs (oral PDE- 5 inhibitors or oral soluble guanylate cyclase s-mulator) oral endothelin antagonists (ERAs) oral, IV, SQ, inhaled prostanoid

9 What the 5th World Symposium Statement and CHEST Guidelines Tell Us: The Five W s Who Where What When Why

10 Who? PH: Mean PAP 25 mmhg PAH IPAH CTD PPHN, HIV Anorexigens 1 Mul-factorial Sarcoidosis mpap 25mmHg PCWP 15 mmhg PVR > 3 Wood units Treatment Guidelines LeT Heart Disease PAH 2 CTEPH* HFrEF HFpEF Valvular 5 PH Sickle Cell Disease from Group I to Group V 4 Thrombo-c Embolic 3 Respiratory Disease Hypoxia Simonneau G et al. J Am Coll Cardiol 2013; 62:D34-41

11 Where? We suggest that, whenever possible, all PAH pa-ents be evaluated promptly at a center with exper-se in the diagnosis of PAH, ideally prior to the ini-a-on of therapy. collabora-ve and closely coordinated care of PAH pa-ents involving the exper-se of both local physicians and those with exper-se in PAH care. Grade of evidence: Consensus- Based Taichman DB et al. Pharmacologic therapy for pulmonary arterial hypertension in adults: CHEST guideline and expert panel report. Chest 2014;146(2):

12 What? And When? Taichman DB et al. Pharmacologic therapy for pulmonary arterial hypertension in adults: CHEST guideline and expert panel report. Chest 2014;146(2):

13 What? General Measures Prevent pregnancy 1,2 Rehabilita-on/Exercise 1 An-coagula-on, diure-cs, digitalis, oxygen 1 Vaccina-on 2 Air travel/al-tude 2 Surgery 2 5th Symposium 2 ACCP Guidelines 1

14 Treatment Selec-on Based on Func-onal Class Differs based on status Treatment- naïve Rela-ve stability vs. Rapid progression Currently on therapy Symptoma-c vs. unacceptable or deteriora-ng clinical status Pa-ent preference Grading systems differ by report

15 Evidence or agreement RCT/meta- analyses Single RCT Large CT Weight in favor Consensus Registries Less well established Galie N et al. J Am Coll Cardiol 2013;62:D60-72.

16 Grade/Evidence Recommenda-on Strong/High: 1A Benefits vs. Risk Clear benefit Methodologic Strength of Evidence Implica-ons Consistent RCT evidence; no limita-ons Most pa-ents Most situa-ons Strong/Moderate: 1B Clear benefit RCT with limita-ons Most pa-ents Most situa-ons* Strong/Low: 1C Clear benefit Flawed RCT with one cri-cal outcome Most pa-ents Many situa-ons Weak/High: 2A Balanced Consistent RCT evidence Strong observa-onal Best ac-on varies by pa-ent Weak/Moderate: 2B Balanced RCT with limita-ons Strong observa-onal Best ac-on varies by pa-ent Weak/Low: 2C Uncertain Observa-onal, case series, Other op-ons or RCT with major flaw reasonable Non- graded: Consensus- Based Uncertain, but expert opinion Insufficient evidence

17 Ini-al Therapy Recommenda-on Recommend Suggest Evidence FC II FC III FC IV Grade 1B Grade 1C Grade 2C Ambrisentan Sildenafil Bosentan Ambrisentan Sildenafil Consensus- Based Bosentan Macitentan Tadalafil Riociguat Macitentan IV epoprostenol Tadalafil IV trepros-nil Riociguat Inhaled Iloprost IV Epoprostenol or Trepros.nil + IV Trepros.nil Bosentan SQ Trepros.nil Taichman DB et al. Pharmacologic therapy for pulmonary arterial hypertension in adults: CHEST guideline and expert panel report. Chest 2014;146(2):

18 Combina-on Therapy Recommenda-on Evidence FC III/FC IV Unacceptable/Deteriora-ng Clinical Status Recommend Suggest Consensus- Based Oral + IV Epoprostenol IV/SQ/inhaled Trepros-nil Inhaled Iloprost Two classes + Third Class

19 When? Clinical Worsening 5th Symposium: WHO FC, exercise capacity, CI, RAP, NT- probnp, echocardiographic parameters, perceived need ACCP Guidelines No defini-on

20 Why? 5th Symposium: no specific goals ACCP Guidelines Specific indica-ons for each agent Improve WHO FC Improve 6MWD Delay -me to clinical worsening Improve cardiopulmonary hemodynamics

21 Limita-ons Despite review of 8,256 cita-ons iden-fied by the ACCP Guideline literature search, how many of the 79 recommenda-ons received an evidence grade (vs. consensus based)? Hemnes AR. Chest 2014;146:

22 To Be Determined Order of ini-a-on ERA vs. NO- agent vs. prostacyclin Ini-al combina-on vs. single agent Outcomes Is all -me- to- clinical worsening the same? RV func-on parameter? Quality of life; Pallia-ve care Other forms of PH?

23 Back to the Pa-ent: Post Test Ques-on 45 yo with SLE- PAH, WHO FC II symptoms with preserved RV func-on. Which of the following is not recommended or suggested as ini-al therapy according to the ACCP Guidelines? Sildenafil Ambrisentan Inhaled iloprost Macitentan

24 Summary: New Guidelines Applies only to adults with PAH Early referral to expert center and ongoing collabora-on with local provider important Stra-fica-on by func-onal class for ini-al selec-on of therapy No recommenda-ons for ini-al class of agent Combina-on therapy recommended for lack of clinical response to ini-al agent