Pulmonary Arterial Hypertension: The Approach to Management in 2019
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1 Pulmonary Arterial Hypertension: The Approach to Management in 2019 Munir S. Janmohamed M.D. FACC Medical Director Mechanical Circulatory Support/Heart Failure Program Mercy General Hospital/Mercy Medical Group Cardiology
2 Disclosures Actelion Novartis Abbott 2
3 Disclosures 3
4 Outline Future Directions Therapy Risk Assessment Hemodynamic Definition WHO Groups 4
5 1st: Geneva, Switzerland nd : Evian, France rd : Venice, Italy th : Dana Point, CA,USA th : Nice, France 2013 World Symposium on PAH: 5
6 Eur Respir J
7 7 Eur Respir J 2018
8 Previous Definition of PH: mpap >25 8
9 Therapeutic Targets for PAH 9
10 10
11 CASE 42 year old female CC: 3 month history of progressive dyspnea initially with climbing stairs, now with daily activities PMX: None Social History: Negative Labs: NT-Pro BNP 700 ECHO: 6 Min walk Test: 400 meters 11
12 CASE RHC: Diagnosis: Idiopathic PAH RA: 13 mpap: 48/22 (31) PAWP: 10 CO: 3.5 TPG: 21 PVR: 6 Negative ino challenge How to Treat? 12
13 Phosphodiesterase inhibitor and and guanylate cyclase stimulators Drug Starting Dose Considerations Sildenafil 20 mg PO TID TID Dosing Tadalafil 20mg PO QD QD Drug Starting Dosing Considerations Riociguat 1 mg PO TID TID Dosing, Hypotension 13
14 Endothelin receptor antagonists (ERAs) Drug Starting Dose Considerations Bosentan 125mg PO BID BID Dosing, Hepatotoxicity Ambrisentan 5mg PO QD QD, Less Hepatoxic Macitentan 10mg PO QD QD, Less Hepatoxic 14
15 Prostacyclin Analogs and prostacyclin receptor agonists Route Drug Route Drug PO Treprostinil SQ Treprostinil PO Selexipag Route Drug Route Drug IV Epoprostenol Inhaled Treprostinil IV Treprostinil Inhaled Iloprost 15
16 Supportive Care Therapy Diuretics O2 Therapy Anticoagulation Indications RHF Hypoxia IPAH, Heritable, Drug Induced from Anorexiants 16
17 Clinical Trials Monotherapy/Placebo Small Numbers/Duration Endpoint: 6 MWT Dana Point 2008 Endpoint: Time to Clinical Worsening 17
18 SERAPHIN Study N ENGL J MED 369;9 NEJM.org August 29,
19 SERAPHIN Study N ENGL J MED 369;9 NEJM.org August 29,
20 SERAPHIN Study 45% Reduction in Primary Endpoint N ENGL J MED 369;9 NEJM.org August 29,
21 N: 500 patients 2:1:1 Tadalafil 40mg plus ambrisentan 10mg PO QS Tadalafil plus plabebo Ambrisentan plus placebo N Engl J Med 2015; 373:
22 AMBITON Study 50% Reduction in Primary Endpoint N ENGL J MED 373;9 nejm.org August 27,
23 GRIPHON Study 23
24 GRIPHON Study 24
25 GRIPHON Trial Death (from any cause) or a complication related to pulmonary arterial hypertension (disease progression or worsening of pulmonary arterial hypertension that resulted in hospitalization, initiation of parenteral prostanoid therapy or long-term oxygen therapy, or the need for lung transplantation or balloon atrial septostomy. 40% RR Sitbon O et al. N Engl J Med 2015;373:
26 Clinical Trials 26
27 Risk Scores 27
28 ESC/ERS PH Guidelines European Heart Journal (2016) 37,
29 Case: 42 year old female with IPAH 6 MWT: 400 Meters Labs: NT-Pro BNP 700 RA: 13 mm Hg 29
30 30
31 Treatment European Heart Journal (2016) 37,
32 Future Developments Genetics Epigenetics DNA Damage Growth Factors Metabolisms Inflammation and immune modulation Ostrogen signaling Oxidative and hypoxic stress Serotonin and humoral modulation Pulmonary Artery denervation Stem cell therapies. 32
33 Summary: Pulmonary Arterial Hypertension: The Approach to Management in 2019 Identification of WHO Group (s), referral to PH Specialist Always reassessing risk given progressive nature of PAH and possible RHF Combination therapy first line Triple Therapy? Need for continued research on novel pathways 33
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