N Engl J Med

The Health Economics of PAH
Harrison (Hap) Farber, MD
Professor of Medicine
Pulmonary Hypertension Center
Boston University/Boston Medical Center
Boston, Massachusetts
R. James White, MD, PhD
Associate Professor of Medicine
Pharmacology and Physiology
University of Rochester School of Medicine
Rochester, New York
PAH Diagnostic Workup
General Considerationsa,b
• Presentation/history suggestive of PH
– Echocardiogram
– ECG, chest radiograph, TTE, PFT, HRCT
– V/Q scan
• Presence of comorbidities (eg, diabetes, obesity,
CAD); echocardiogram suggestive of PH 
diastolic dysfunction?
– Initiate empiric loop diuretics
– Sleep study  undiagnosed sleep apnea?
a. Galie N, et al. Eur Heart J. 2009;30:2493-2537[2]; b. McGoon et al. Chest. 2004;126(1
When to Perform an RHC?a,b
• Patient responding to empiric therapy: loop
diuretics, apnea therapy?
– Yes  no further testing (ie, probable diastolic
– No  comprehensive guideline-recommended
workup vs immediate RHC?
Prior history and diagnostic workup (ie, referral population)
Rule out left heart disease, sleep apnea
Immediate RHC is more cost-effective vs complete
mPAP ≥ 25 mm Hg; PWP ≤ 15 mm Hg  proceed with
guideline-directed workup
a. Galie N, et al. Eur Heart J. 2009;30:2493-2537[2]; b. McGoon et al. Chest. 2004;126(1
suppl):14S-34S[3]; c. Taylor B, et al. J Heart Lung Transplant. 2013;32:137-138.[1]
Cost of Hospitalizations in PAH
Registry and Trial Data
• REVEAL Registrya
– Mean total hospital days in the year after first admission for all
pts with ≥ 1 hospitalization: 15.3 days (median: 7.0 days)
– Estimated 2012 total costs (inpatient and outpatient) for PAH:
$188 million
• Estimated average cost/hospitalizationb
– ~ $60,000-$100,000 (average 3-night stay on telemetry unit)
• AMBITION datac
– NNT to prevent 1 hospitalization: 9
– QALY: ~ $90,000-$100,000 or higher for longer hospital stays?
– Combination therapy for shorter, less intense hospitalizations?
a. Burger CD, et al. Chest. 2014;146:1263-1273[4]; b. Johnson S, et al. J Med Econ. 2013;16:14141422[5]; c. Galiè N. ERS 2014. Abstract 2916.[6]
PAH Inpatient Management
• Echocardiogram
• CT scan
• IV inotropes, prostacyclins
• Anticoagulants
• Supplemental oxygen, CPAP
• Continuous monitoring
McGoon M, et al. Mayo Clin Proc. 2009;84:191-207.[3]
Reducing Hospitalizations
Impact of Current and Emerging Therapies
• Macitentan (ERA): SERAPHIN triala,b
Included pts on macitentan monoand combination therapy (PDE-5
inhibitors, oral or inhaled prostanoids,
CCBs, l-arginine)
Macitentan reduced primary end point
(composite of death, atrial
septostomy, lung transplantation,
initiation of treatment with IV or SC
prostanoids, worsening PAH) by
30%-45% (dose dependent; P = .01;
P < .001)
Reduced all-cause hospitalization by
32% (HR, 0.677; P = .0051)
• Ambrisentan (ERA) ± tadalafil
(PDE-5 inhibitor) vs monotherapy:
Reduced clinical failure events by
50% (HR, 0.502; P = .0002);
superior to each individual
monotherapy (P < .01)  main
treatment effect driven by
• Selexipag (selective IP receptor
agonist): GRIPHON top-line datad
80% of pts receiving oral PAH
therapy at onset
Reduced morbidity/mortality event
vs placebo by 39% (P < .0001)
a. Pulido T, et al. N Engl J Med. 2013;369:809-818[8]; b. Mehta S, et al. ATS 2014. Abstract B17[9];
c. Galiè N, et al. ERS 2014. Abstract 2916[6]; d. Actelion press release.[10]
Early, Aggressive PAH Therapy
Effect on Outcomes
• Hospitalization
– Number
– Duration
– Utilization of resources
• Patient satisfaction/QOL
– Hospital-acquired infections/conditions
• Morbidity and mortality events
a. Pulido T, et al. N Engl J Med. 2013;369:809-818[8]; b. Mehta S, et al. ATS 2014. Abstract B17[9];
c. Galiè N, et al. ERS 2014. Abstract 2916[6]; d. Actelion press release [website].[10]
The Real Cost of PAH Drugs
Oral Treprostinila,b
History of expensive PAH drugs
• IV epoprostenol/SC treprostinil: ~ $90,000/year
• Bosentan: ~ $80,000/year
• Ambrisentan: ~ $80,000/year
• Oral treprostinil
– ~ $500,000/year [12 mg, three times daily  patients
transitioning from parenteral treprostinil (ongoing trialc)]
– Compared with placebo: improved 6MWD, Borg
dyspnea score (intent-to-treat population  26.0 m; P =
a. McLaughlin VV, et al. Circulation. 2009;119:2250-2294[11]; b. Frumkin LR, et al. Pharmacol Rev.
2012;64(3):583-620.[12]; c. White RJ, et al. ATS 2013. Abstract B64.[13]; d. Jing ZC, et al. Circulation.
The Real Cost of PAH Drugs
Soluble guanylate cyclase stimulator
• PATENT-1, randomized, phase 2 trial (PAH)a
Significant improvement
• 6MWD
• PVR (P < .001)
• NT-proBNP levels (P < .001)
• WHO FC (P = .003)
• TTCW (P = .005)
• Borg dyspnea score (P = .002)
• CHEST-1, randomized, phase 3 trial (CTEPH)b
Significant improvement in
• PVR (P < .001)
• NT-proBNP level (P < .001)
• WHO FC (P = .003)
• Cost: $7500/monthc
Compared with tadalafil or generic sildenafil ($10,000-$12,000/year)d
a. Ghofrani HA, et al. N Engl J Med. 2013;369:330-340[14]; b. Ghofrani HA, et al. N Engl J Med.
2013;369:319-329[16]; c. Walker T. Drug Topics. October 10, 2013[17]; d. McLaughlin VV, et al. Circulation.
• Cost-effectiveness of PAH therapies will
continue to be an issue, despite their
improving efficacy
• Efficacy, tolerability, and ease of use have
to be balanced with costs to payers (ie,
insurers, employers, government agencies)
6MWD = 6-minute walk distance
CAD = coronary artery disease
CCB = calcium channel blocker
CPAP = continuous positive airway pressure
CT = computed tomography
CTEPH = chronic thromboembolic pulmonary hypertension
ECG = echocardiogram
ERA = endothelin receptor antagonist
FDA = US Food and Drug Administration
HR = hazard ratio
HRCT = high-resolution computer tomography
IP = intraperitoneal
mPAP = mean pulmonary artery pressure
NNT = number needed to treat
NT-proBNP = N-terminal pro-brain natriuretic peptide
PAH = pulmonary arterial hypertension
PFT = pulmonary function test
PH = pulmonary hypertension
Abbreviations (cont)
PVR = pulse volume recording
QALY = quality-adjusted life-year
QOL = quality of life
RHC = right heart catheterization
SC = subcutaneous
TTCW = time to clinical worsening
TTE = transthoracic echocardiogram
WHO FC = World Health Organization functional class
1. Taylor B, Rumbak M, Taylor SP, Solomon D. Early versus delayed right heart
catheterization in evaluation of pulmonary arterial hypertension. J Heart Lung
Transplant. 2013;32:137-138.
2. Galiè N, Hoeper MM, Humbert M, et al. Guidelines for the diagnosis and treatment
of pulmonary hypertension: the Task Force for the Diagnosis and Treatment of
Pulmonary Hypertension of the European Society of Cardiology (ESC) and the
European Respiratory Society (ERS), endorsed by the International Society of Heart
and Lung Transplantation (ISHLT). Eur Heart J. 2009;30:2493-2537.
3. McGoon M, Gutterman D, Steen V, et al. Screening, early detection, and diagnosis
of pulmonary arterial hypertension: ACCP evidence-based clinical practice
guidelines. Chest. 2004;126(1 suppl):14S-34S.
4. Burger CD, Long PK, Shah MR, et al. Characterization of first-time hospitalizations
in patients with newly diagnosed pulmonary arterial hypertension in the REVEAL
registry. Chest. 2014;146:1263-1273.
References (cont)
5. Johnson S, Delate T, Boka A, et al. Characterizing the financial burden of
pulmonary arterial hypertension within an integrated healthcare delivery system. J
Med Econ. 2013;16:1414-1422.
6. Galiè N. The AMBITION study: design and results. Presented at: 2014 European
Respiratory Society Annual Meeting; June 9-14, 2014; Munich, Germany. Abstract
7. McGoon MD, Kane GC. Pulmonary hypertension: diagnosis and management.
Mayo Clin Proc. 2009;84:191-207.
8. Pulido T, Adzerikho I, Channick RN, et al. Macitentan and morbidity and mortality
in pulmonary arterial hypertension. N Engl J Med. 2013;369:809-818.
9. Mehta S, Delcroix M, Galiè N, et al. Macitentan reduced all-cause hospitalizations
in patients with pulmonary arterial hypertension: data from the randomized controlled
SERAPHIN trial. Presented at: 2014 American Thoracic Society Annual Meeting;
May 16-21, 2014; San Diego, CA. Abstract A2458.
References (cont)
10. Actelion press release. Selexipag meets primary endpoint in pivotal phase III
GRIPHON outcome study in patients with pulmonary arterial hypertension.
Accessed December 15, 2014.
11. McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 expert
consensus document on pulmonary hypertension: a report of the American College
of Cardiology Foundation Task Force on Expert Consensus Documents and the
American Heart Association: developed in collaboration with the American College of
Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension
Association. Circulation. 2009;119:2250-2294.
12. Frumkin LR. The pharmacological treatment of pulmonary arterial hypertension.
Pharmacol Rev. 2012;64(3):583-620.
13. Jing ZC, Parikh K, Pulido T, et al. Efficacy and safety of oral treprostinil
monotherapy for the treatment of pulmonary arterial hypertension: a randomized,
controlled trial. Circulation. 2013;127:624-633.
References (cont)
14. White RJ, Chakinala MM, Mathier M, et al. Safety and tolerability of transitioning
from parenteral treprostinil to oral treprostinil in patients with pulmonary arterial
hypertension. Presented at: 2013 American Thoracic Society Annual Meeting; May
17-23, 2013; Philadelphia, PA. Abstract A3303.
15. Ghofrani HA, Galiè N, Grimminger F, et al. Riociguat for the treatment of
pulmonary arterial hypertension. N Engl J Med. 2013;369:330-340.
16. Ghofrani HA, D'Armini AM, Grimminger F, et al. Riociguat for the treatment of
chronic thromboembolic pulmonary hypertension. N Engl J Med. 2013;369:319-329.
17. Walker T. FDA approves first drug to treat two forms of pulmonary hypertension.
Drug Topics. October 10, 2013. http://drugtopics.modernmedicine.com/drugtopics/content/clinical/clinical-pharmacology/fda-approves-first-drug-treat-two-formspulmonary?page=full. Accessed December 15, 2013.

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