Presentation on theme: "Learning Objectives Utilize knowledge regarding the specific disease pathways for PAH in order to identify the sites and targets for common therapies,"— Presentation transcript:
Learning Objectives Utilize knowledge regarding the specific disease pathways for PAH in order to identify the sites and targets for common therapies, including prostacyclin analogs, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors. Evaluate patients for comorbid conditions to determine the relative risk for PAH. Use evidence-based guidelines to select the most appropriate treatment. Apply determinants of risk to assess a patient’s prognosis and recognize when therapy needs to be augmented. Compare the side effect profiles and drug interaction potential of available PAH treatments to gauge the risk-benefit ratio of each option and to determine areas for patient monitoring.
Overview of PAH US prevalence = estimates up to 50,000 to 100,000 –15,000 to 25,000 diagnosed and treated Disease of small pulmonary arteries characterized by vascular narrowing and increased vascular resistance –Vasoconstriction –Cell proliferation and pulmonary vascular remodeling –Thrombosis in situ Common cause of death: Right ventricular (RV) failure Humbert, et al. J Am Coll Cardiol. 2004;43:13S-24S.
Mechanisms of Pathology for PAH Humbert, et al. N Engl J Med. 2004;351: Nitric oxide cGMP Vasodilatation and antiproliferation Endothelial cells Nitric oxide pathway PreproendothelinProendothelin L-arginine NOS Arachidonic acidProstaglandin I 2 cAMP Vasodilatation and antiproliferation Vasoconstriction and proliferation Endothelin- receptor A Endothelin- receptor B Endothelin pathwayProstacyclin pathway Endothelin-1 Endothelin- receptor antagonists Exogenous nitric oxide Prostacyclin derivates Phosphodiesterase type 5 inhibitor Phosphodiesterase type 5
Pathophysiology of PAH Genetic Predisposition Other Risk Factors (CTD, CHD, toxins, etc.) Altered Pathways And Mediators Vasoconstriction Cell Proliferation Thrombosis Vascular Remodeling }
Genetic Mutations in PAH Mutations in the gene that codes for BMPR2 –BMPR2 mutations are identified in ~ 70% of patients with heritable PAH –BMPR2 mutations are also found in ~ 20% of patients with I-PAH »Clinical course – poor response to acute vasodilator testing and treatment with calcium channel blockers Mutations in the gene that codes for: –Activin receptor-like kinase type 1 (ALK1) –Endoglin (ENG) »Cause hereditary hemorrhagic telangiectasia (HHT) and may lead to the development of PAH Machado, et al. J Am Coll Cardiol. 2009;54:S32-42.
Cell Proliferation in PAH High PVR Proliferative / angiogenic / apoptosis resistant –↑ Endothelin, serotonin (5-HT), VEGF, BMPR2 and ALK1 mutations –↓ Potassium channel expression/activity
Vascular Remodeling in PAH Poorly understood PAH cells are pro-proliferative Many factors implicated in pro-proliferative phenotype Proliferative and obstructive remodeling of the pulmonary vessel wall Some new therapies aimed at controlling cell growth Several potential mediators –Alterations in gene expression in growth-controlling pathways –Growth factors –Inflammatory mediators Galie, et al. Eur Heart J. 2009;30:
Revised Classification of Pulmonary Hypertension Group 1: Pulmonary Arterial Hypertension (PAH) Criteria mPAP ≥ 25 mm Hg PCWP 15 mm Hg No significant: –Obstructive/Restrictive lung disease –Left heart disease –Thromboembolic disease Types Idiopathic PAH Heritable PAH –BMPR2, ALK1, Endoglin Drug- and toxin-induced Associated with: –Connective tissue disease –HIV –Portal pulmonary –Congenital heart diseases –Schistosomiasis –Chronic hemolytic anemia Persistent pulmonary hypertension of the newborn Simonneau, et al. J Am Coll Cardiol. 2009;54:S43-54.
Differential Diagnosis of PAH Clinical presentation Electrocardiogram (ECG) Chest radiograph Pulmonary function tests and arterial blood gases ECHO (right heart hemodynamics) Ventilation / perfusion lung scan High-resolution CT, contrast CT, pulmonary angiography Cardiac MRI Blood tests and immunology Abdominal ultrasound scan Right heart catheterization and vasoreactivity Galie, et al. Eur Heart J. 2009;30:
Invasive Diagnostic Testing for PAH Right heart catheterization –Mandatory for all patients being tested for PAH –Pulmonary arterial pressure (PAP) –Cardiac output (CO) –Right atrial pressure (RAP) –Pulmonary arterial wedge pressure (PAWP) Badesch, et al. J Am Coll Cardiol. 2009;54:S55-66.
Prevalence of PAH in Associated Conditions 4 th World Symposium on PH (2008) Associated ConditionPrevalence of PAH Systemic sclerosis7-12 % HIV infection % Portal hypertension2-6 % Congenital heart disease per million in those with congenital systemic-to- pulmonary shunts → % affected by Eisenmenger syndrome Schistosomiasis4.6 % in those with hepatosplenic disease Chronic hemolytic anemiaHighly variable; currently being studied Simonneau, et al. J Am Coll Cardiol. 2009;54(1):S43-54.
Patient Evaluation Confirm presence of PH Determine type of PH present (PAH?) Gauge functional capacity Estimate prognosis (survival) Determine treatment and monitoring plan
NYHA/WHO Functional Classification for PAH Class I No limitation of physical activity. Ordinary physical activity does not cause undue dyspnea, fatigue, chest pain, or near syncope. Class II Slight limitation of physical activity; no discomfort at rest. Ordinary activity causes undue dyspnea, fatigue, chest pain, or near syncope. Class III Marked limitation of physical activity; no discomfort at rest. Less than ordinary physical activity causes undue dyspnea, fatigue, chest pain, or near syncope. Class IV Inability to perform any physical activity without symptoms; signs of right ventricular failure or syncope; dyspnea and/or fatigue may be present at rest; discomfort is increased by any physical activity. Taichman, et al. Clin Chest Med. 2007;28:1-22.
Predicting Survival in PAH Hemodynamics Response to acute vasodilator therapy (calcium channel blockers, CCB) Exercise capacity NYHA/WHO functional class Biomarkers (i.e., BNP levels) Badesch, et al. J Am Coll Cardiol. 2009;54:S55-66.
Years Long-term CCB responders (~50% of acute responders or ≤ 6% of IPAH patients) Long-term CCB non-responders Patients at risk (N) Cumulative Survival Long-term CCB responders Long-term CCB non-responders Sitbon, et al. Circulation. 2005;111: P = Response to CCB Therapy and Survival in Patients with PAH
Impact of Delay in Treatment on Patient Survival ABSTRACT: McLaughlin, et al. Am J Respir Crit Care Med. 2008;177:A697. N = Ambrisentan N = Placebo → Ambrisentan Event-Free Survival (% Patients) 86% 96% 84% 76% ↑ Transition placebo group to ambrisentan Weeks
Goals for Patients with PAH Ultimate goals –Feel better –Do more –Live longer Gap in understanding → ?Promote vasorelaxation ?Suppress cellular proliferation ?Induce apoptosis within pulmonary artery wall Archer, et al. N Engl J Med. 2009;361:
Amlodipine, diltiazem, nifedipine (B) YES ACUTE RESPONDER WHO Class I-IV Amlodipine, diltiazem, nifedipine (B) Sustained response (WHO I-II) Atrial septostomy (E/B) and/or lung transplant (E/A) INADEQUATE CLINICAL RESPONSE NO PAH Evidence-Based Treatment Algorithm Acute vasoreactivity test (A for IPAH) (E/C for APAH) Expert referral (E/A) Supportive therapy and general measuresAvoid excessive physical exertion (E/A) Birth control (E/A) Psychosocial support (E/C) Infection prevention (E/A) Oral anticoagulants (E/B) – IPAH/HPAH Diuretics (E/A) Oxygen (E/A) Digoxin (E/C) Supervised rehabilitation (E/B) Strength of RecommendationWHO Class IIWHO Class IIIWHO Class IV A Ambrisentan, Bosentan, Sildenafil Ambrisentan, Bosentan, Epoprostenol IV, Iloprost inh, Sildenafil Epoprostenol IV B Sitaxsentan, TadalafilSitaxsentan, Tadalafil, Treprostinil SC Iloprost inh CBeraprostTreprostinil SC E/B Iloprost IV, Treprostinil IV Initial combination therapy (see below) E/C Ambrisentan, Bosentan, Sildenafil, Sitaxsentan, Tadalafil Not approvedTreprostinil inh Sequential combination therapy PDE-5 IERA + (B) Prostanoids NON-RESPONDER 4 th World Symposium on PH. Dana Point, CA Barst, et al. J Am Coll Cardiol. 2009;54:S INADEQUATE CLINICAL RESPONSE
Acute Vasoreactivity Test for PAH Calcium Channel Blockers (CCB) –Acute vasoreactive response = –Positive response in < 10% of patients with IPAH –Responders are on higher than ordinary doses of CCB: amlodipine 10 mg twice daily; diltiazem 360 mg twice daily –Moderate recommendation based on scientific evidence Barst, et al. J Am Coll Cardiol. 2009;54:S Reduction of mean PAP ≥ 10 mm Hg to reach a mean PAP ≤ 40 mm Hg with a normalized or increased CO with acute pulmonary vasodilator challenge with either inhaled NO or IV epoprostenol
FDA-Approved Agents for the Treatment of PAH Prostacyclin analogs (PA) –Epoprostenol –Iloprost –Treprostinil Endothelin-receptor antagonists (ERA) –Ambrisentan –Bosentan Phosphodiesterase-5 inhibitors (PDE-I) –Sildenafil –Tadalafil
Comparison of Agents Agent Route of AdministrationAdverse Events EpoprostenolContinuous IV infusion Headache, jaw pain, flushing, nausea, diarrhea, skin rash, musculoskeletal pain IloprostInhalationHeadache, cough, flushing, jaw pain Treprostinil» Subcutaneous » IV » Inhalation* » Pain and erythema at injection site, headache, nausea, diarrhea, rash » Headache, jaw pain, flushing, nausea, diarrhea, skin rash, musculoskeletal pain » Cough, headache, flushing, throat irritation, nausea AmbrisentanOralHepatotoxicity (LFT elevation ≥ 3x ULN ~ 2.8%), peripheral edema BosentanOralHepatotoxicity (LFT elevation ≥ 3x ULN ~ 11%), peripheral edema, anemia SildenafilOralHeadache, flushing, dyspepsia, epistaxis TadalafilOralHeadache, dyspepsia, back pain, myalgia, flushing Adapted from McLaughlin, et al. J Am Coll Cardiol. 2009;53: *Benza, et al. ATS. San Diego, CA. May 15-20, 2009.
CADD pumpCentral line Epoprostenol for PAH Prostacyclin analog Indication – WHO group I - functional class III, IV Administration – continuous IV infusion via central venous catheter Dosage – ng/kg/min Storage – must keep medication cold with ice packs (stable for 8 hours at room temp)
Weeks Epoprostenol (N=41) Conventional therapy (N = 40) Epoprostenol for IPAH Patient Survival Patient Survival (%) P = Barst, et al. N Engl J Med. 1996;334:
Prostacyclin analog Indication – WHO group I - functional class III, IV Administration –Ultrasonic nebulizer –Dosage = 2.5 to 5 g, 6 to 9 times daily; maximum daily dosage evaluated in clinical studies = 45 g –Administration in well-ventilated areas Theoretical advantage of selectivity –Pulmonary vs systemic administration Iloprost for PAH
Iloprost for PAH Composite Primary Endpoint at Week 12 Olschewski, et al. N Engl J Med. 2002;347: Responders (% Patients) P = N = 203
Treprostinil for PAH Prostacyclin analog Indication – WHO group I - functional class II, III, IV Dosage – 1.25 – 40 ng/kg/min Administration –Subcutaneous –IV –Inhalation Infusion site reaction
Treprostinil SC for PAH Change in 6-MWD (from Baseline to Week 12) < 5.0 ng/kg/min ng/kg/min 8.2 – 13.8 ng/kg/min > 13.8 ng/kg/min Change from Baseline (meters) P = 0.03 Simonneau, et al. Am J Respir Crit Care Med. 2002;165: N = 470
Treprostinil IV for PAH Change from Baseline to Week 12 Change in 6-MWD Change from Baseline (meters) Tapson, et al. Chest. 2006;129: Weeks Number of Patients Change in Functional Class 12 Weeks Baseline N = 14
Treprostinil Inhalation for PAH: TRIUMPH-1 Clinical Trial Treprostinil inhalation FDA approval – July, 2009 Administered four times daily Study design – phase lll, randomized, double-blind, placebo-controlled, 12- week study Combination with bosentan or sildenafil Open-label extension for 24 months N= 206 Adverse events – cough, headache, nausea, diarrhea, flushing, throat irritation Months Change in 6-MWD from Baseline (meters) ABSTRACT: Benza, et al. ATS. San Diego, CA. May 15-20, 2009.
Endothelin Receptor Antagonists Comparison of Agents Source: FDA-approved product labeling for individual agents. BosentanAmbrisentan Use in pregnancyPregnancy category X (non- hormonal birth control method required) LFT elevationMonthly LFT monitoring required; ≥ 3x ULN in ~ 11% patients (pooled data from 16-week studies) Monthly LFT monitoring required; ≥ 3x ULN in 0.8% patients in 12-week studies, 2.8% patients in 1-year studies Peripheral edema1.7% patients (placebo-adjusted; fluid retention/edema) 6% patients (placebo-adjusted) Additional adverse events Respiratory tract infections, headache, fainting, flushing, low blood pressure, sinusitis, joint pain, irregular heartbeat Nasal congestion, sinusitis, flushing, palpitations, nasopharyngitis, abdominal pain, constipation
Endothelin Receptor Antagonists Comparison of Drug-Drug Interactions Source: FDA-approved product labeling for individual agents. 1) Barst, et al. J Am Coll Cardiol. 2009;54:S ) Galie, et al. Eur Heart J. 2009;30: ) Spence, et al. ATS. San Diego, CA. May 15-20, ) Harrison, et al. ATS. San Diego, CA. May 15-20, BosentanAmbrisentan Ritonavir Rifampin Cyclosporine A Hormonal contraceptives Sildenafil Tadalafil 1 Glyburide Simvastatin (+ other CYP3A-metabolized statins) CYP2C9 inhibitors (fluconazole, amiodarone) CYP3A inhibitors (ketoconazole, itraconazole, amprenavir, erythromycin, fluconazole, diltiazem) Tacrolimus Phenytoin 2 Warfarin 2 Ritonavir Rifampin Cyclosporine A Hormonal contraceptives 3 Omeprazole 4 Ketoconazole 2,4
Bosentan for PAH Endothelin receptor antagonist (ET A /ET B non selective) Indication – WHO group I - functional class II, III, IV Dosage – 62.5 mg oral twice daily for 4 weeks then 125 mg oral twice daily
62.5 mg bid 125 or 250 mg bid Bosentan Bosentan (N= 144) Placebo (N= 69) BaselineWeek 4Week 8Week 16 P = Change from Baseline (meters) Rubin, et al. N Engl J Med. 2002;346: Bosentan for PAH: BREATHE Clinical Trial Change in 6-MWD (from Baseline to Week 16)
Bosentan for PAH Comparison of 6-MWD in 6-Month, Open-Label Study Sitbon, et al. Chest. 2003;124: Six-month, open-label study of bosentan (125 mg bid) after a double-blind, placebo-controlled, four-month study Delay in treatment in former placebo patients → less robust improvement in 6-MWD during open-label extension N= 29 Change from Baseline (meters)
Bosentan for PAH: EARLY Clinical Trial Change in PVR (from Baseline to Week 24) Galie, et al. Lancet (9630): Valerio et al. Vasc Health Risk Manag. 2009;5: % of Baseline PVR at Week 24 (geometric means) P < Decrease in PVR: Surrogate marker for delaying disease progression Treatment effect = %
Bosentan for PAH: EARLY Clinical Trial 10 5 weeks Placebo (N= 91) Bosentan (N= 86) P = 20 1515 Change in 6-MWD (from Baseline to Week 24) Treatment effect = meters Change in 6-MWD (meters) Galie, et al. Lancet (9630): Valerio et al. Vasc Health Risk Manag. 2009;5: weeks
Bosentan for PAH: EARLY Clinical Trial Event-Free Patients (%) Patients at risk (N) Placebo Bosentan P < 0.02 Time to Clinical Worsening (from Baseline to Week 32) weeks Galie, et al. Lancet (9630): Valerio et al. Vasc Health Risk Manag. 2009;5:
Ambrisentan for PAH Endothelin receptor antagonist (ET A selective) Indication – WHO group I - functional class II, III Dosage – 5 mg and 10 mg oral daily
Ambrisentan for PAH Change in 6-MWD (from Baseline to Week 12) Galie, et al. Circulation. 2008;117: weeks 10 mg: m 5 mg: m Placebo: -7.8 m N= weeks 5 mg: m 2.5 mg m Placebo: m N=192 Change from Baseline (meters) ARIES 1 ARIES 2 Placebo-adjusted change at week 12: Ambrisentan 5 mg = 31 m; 10 mg = 51 m Placebo-adjusted change at week 12: Ambrisentan 2.5 mg = 32 m; 5 mg = 59 m
Ambrisentan for PAH: ARIES 1 and 2 Clinical Trials Time to Clinical Worsening --- Placebo mg (P = 0.03) mg (P = 0.005) mg (P = 0.03) Weeks Event-Free Patients (%) Ambrisentan → 71% relative risk reduction Galie, et al. Circulation. 2008;117:
Ambrisentan for PAH: ARIES-E Change in 6-MWD (from Baseline to 24 Months) Mean ± 95% CI; LOCF for missing data Change from Baseline (meters) 2.5 mg (N = 93) 5 mg (N = 186) 10 mg (N = 96) Years m 23 m 28 m Oudiz, et al. J Am Coll Cardiol. 2009;54(21):
Ambrisentan for PAH: ARIES-E Change in WHO Functional Class Years Patients (%) Maintained or Improved Worsened 2.5 mg (N= 94) 5 mg (N = 187) 10 mg (N = 96) LOCF for missing data 79% 86% 90% 10% 14% 21% Oudiz, et al. J Am Coll Cardiol. 2009;54(21):
Sildenafil for PAH PDE-5 inhibitor Indication – to increase exercise capacity, decrease clinical worsening in patients with WHO group I – functional class II, III, IV Dosage – 20 mg oral three times daily IV formulation –Approved December, 2009 –Dosage – 10 mg three times daily
Sildenafil for PAH: SUPER Clinical Trial Change in WHO Functional Class (from Baseline to Week 12) Placebo (N= 70) Sildenafil (N= 203) Patients (%) 0% 20% 40% 60% 80% 100% BaselineWeek 12BaselineWeek 12 Class IClass IIClass IIIClass IV Galie, et al. N Engl J Med. 2005;353:
Sildenafil for PAH: Long-Term Extension of SUPER Clinical Trial Change in 6-MWD (from Baseline) Change from Baseline (meters) (N= 222) (N= 273) Galie, et al. N Engl J Med. 2005;353:
Sildenafil for PAH: SUPER 2 Clinical Trial Study design –Open-label, long-term extension of SUPER clinical trial Patients –N= 259 enrolled; 180 completed 3 years of follow-up Dosage = mg three times daily Study results at 3 years –Functional class – improved in 30%; unchanged in 31% –Kaplan-Meier estimated survival = 79% –Patient disposition – 53 patients died (29%); 44 discontinued therapy (24%) –Combination therapy – 20% –Adverse effects – mild/moderate in severity ABSTRACT: Rubin, et al. CHEST. Philadelphia, PA. Oct , 2008.
Tadalafil for PAH FDA approval – May, 2009 PDE-5 inhibitor Indication – to increase exercise capacity, decrease clinical worsening in patients with WHO group I – functional class II, III, IV Dosage – 40 mg oral daily
Tadalafil for PAH: PHIRST Clinical Trial Subgroup analysis: Study design – phase lll, double- blind, placebo-controlled, multicenter, 16-week study Comparison of tadalafil monotherapy (N= 189) to combination therapy with bosentan 125 mg twice daily (N= 216) Dosage of tadalafil = 20 mg and 40 mg Study results No greater improvement in 6-MWD with combination therapy compared to monotherapy ABSTRACT: Barst, et al. ATS. San Diego, CA. May 15-20, Pepke-Zaba, et al. Curr Med Res Opin. 2009;25(10): Change in 6-MWD from Baseline (meters)
Tadalafil for PAH: PHIRST Clinical Trial Study Results Efficacy –Greater improvement in 6-MWD in treatment-naïve patients compared to patients with background bosentan –Significant improvements in quality of life and time to and incidence of clinical worsening (68% relative risk reduction) Safety –Most common adverse events were headache, myalgia, and flushing which were mild to moderate in severity Galie, et al. Circulation. 2009;Epub May 26. Pepke-Zaba, et al. Curr Med Res Opin. 2009;25(10):
Tadalafil for PAH: PHIRST Clinical Trial Pepke-Zaba, et al. Curr Med Res Opin. 2009;25(10): P< 0.01 vs Placebo Mean Change from Baseline to Week 16 Short Form 36 (SF-36) Domains Quality of life measure: Higher scores reflect better functioning and health status
Tadalafil for PAH: Long-Term Extension of PHIRST Study design – phase lll, double-blind, placebo-controlled study (16 weeks) → long-term extension study (44 weeks) Dosage = 20 mg and 40 mg N = 241 Study results Efficacy 6-MWD: sustained improvement over 44 weeks Safety 62 patients withdrew from study including: 17 due to PAH progression; 12 due to adverse events; 11 due to death ABSTRACT: Oudiz, et al. ATS. San Diego, CA. May 15-20, ABSTRACT: Oudiz, et al. ERS. Vienna, Austria. September 14, Change in 6-MWD from Baseline (meters) Weeks
Low RiskDeterminants of RiskHigh Risk NoClinical evidence of RV failureYes GradualDisease progressionRapid II, IIIWHO functional classIV Longer (> 400 meters)6-MWDShorter (< 300 meters) Peak VO 2 > 10.4 mL/kg/minCardiopulmonary exercise testingPeak VO 2 < 10.4 mL/kg/min Minimally elevated and stableBNP/NT-proBNPSignificantly elevated PaCO 2 > 34 mm HgBlood gassesPaCO 2 < 32 mm Hg Minimal RV dysfunctionECHO findings Pericardial effusion, RV dysfunction, RA enlargement RAP < 10 mm Hg; CI > 2.5 L/min/m 2 Hemodynamics RAP > 20 mm Hg; CI < 2 L/min/m 2 McLaughlin, et al. Circulation. 2006;114: McLaughlin, et al. J Am Coll Cardiol. 2009;53: PAH Determinants of Patient Risk ACC/AHA Expert Consensus
Combination Therapy for PAH To target multiple disease pathways –Endothelin pathway (endothelin receptor antagonists) –Nitric oxide pathway (PDE-5 inhibitors) –Prostacyclin pathway (prostacyclin analogs) Used clinically with little evidence to date Used when therapy needs to be augmented because patient response to monotherapy is inadequate Must consider the drug interaction potential of agents to be combined (risk-benefit analysis) –Drug interaction between bosentan and sildenafil –Drug interaction between bosentan and tadalafil Barst, et al. J Am Coll Cardiol. 2009;54:S78-84.
Combination Therapy for PAH TTCW = time to clinical worsening; NSS = non-statistically significant; SS = statistically significant 1) Humbert, et al. Eur Respir J. 2004;24: ) McLaughlin, et al. Am J Respir Crit Care Med. 2006;174: ) Hoeper, et al. Eur Respir J. 2006;28: ) Simonneau, et al. Ann Intern Med. 2008;149: ) Galie, et al. Circulation. 2009;119(22): Clinical StudyAgentsStudy DesignNStudy EndpointsStatistical Significance Humbert, et al 1 Epoprostenol Bosentan Randomized, double- blind, placebo-controlled; 16 weeks 33Hemodynamics, exercise capacity, functional class NSS findings McLaughlin, et al 2 Iloprost Bosentan Randomized, double- blind, placebo-controlled, multicenter; 12 weeks 67Hemodynamics, exercise capacity, functional class, TTCW SS improvement in parameters Hoeper, et al 3 Iloprost Bosentan Randomized, placebo- controlled, multicenter; 12 weeks 40Exercise capacity, functional class, TTCW NSS findings Simonneau, et al 4 Epoprostenol Sildenafil Randomized, double- blind, placebo-controlled, multicenter; 16 weeks 256Hemodynamics, exercise capacity, TTCW SS improvement in exercise capacity, TTCW Galie, et al 5 Bosentan Tadalafil Randomized, double- blind, placebo-controlled; 16 weeks 405Hemodynamics, exercise capacity, functional class, TTCW, quality of life SS improvement in all parameters, except functional class
Monitoring Schedule for Patients with PAH ParameterBaseline (pretreatment) Every 3-6 months 3-4 Months after start or change in therapy If clinical worsening Clinical assessment WHO functional class ECG XXXX 6-MWD XXXX Cardiopulmonary exercise testing XXX BNP/NT-proBNP XXXX ECHO XXX Right heart catheterization XXX Galie, et al. Eur Heart J. 2009;30:
Summary Comprehensive management of PAH involves optimizing multiple supportive therapies Early, evidence-based treatment of PAH is associated with improved patient outcomes Agents for the treatment of PAH vary with regard to: –Indication, administration, adverse effect profile, drug-drug interactions, clinical study data Therefore, a comparison of the risk-benefit ratio of available agents is needed to guide PAH treatment selection