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Medication Adherence and Risk of Hospitalization in Pulmonary Arterial Hypertension (PAH) Patients Treated with Endothelin Receptor Antagonists (ERAs) or Phosphodiesterase Type 5 Inhibitors (PDE5Is)

Michele Cole

JW Hill

Cassandra Lickert

RL Wade

William Drake


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Conference: 2018 PHA International PH Conference & Scientific Sessions

Release Date: 06.28.2018

Presentation Type: Abstracts

File Download: Conference 2018_1025

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2018 International PH Conference and Scientific SeAbstract presented at the 2018 International PH Conference and Scientific Sessions in Orlando, Fla., June 28-July 1, 2018.


To evaluate the relationship between adherence and risk of hospitalization in PAH patients treated with ERAs or PDE5Is.


Pulmonary arterial hypertension (PAH) is a rare, progressive disease characterized by increasing pulmonary vascular resistance and pressure. There are 13 approved PAH-specific medications in the United States (US) targeting three distinct pathways. In addition to clinical trials, real world evidence provides information on adherence and outcomes of PAH treatments.


The PharMetrics Plus claims database consisting of medical and pharmacy claims for more than 150 million patients in the US was used to identify PAH patients between 1/1/2009-6/30/2015 (first Rx claim = index date). Inclusion required one inpatient or ≥2 outpatient claims > 30 days apart with a diagnosis code for PH (ICD-9 codes 416.0 or 416.8) and a prescription for an ERA (ambrisentan, bosentan, or macitentan) or a PDE5i (sildenafil or tadalafil). Erectile dysfunction doses were excluded. Patients had continuous health plan enrollment ≥3 months pre- and ≥6 months post-index. Proportion of days covered (PDC) were compared between ERA and PDE5i. Relationships between medication adherence measured by PDC, percent hospitalized, and mean hospitalizations were analyzed with descriptive statistics and modified Cox regression using a time-varying measure of PDC.


755 ERA and 1,578 PDE5i patients were identified. Mean age of the PDE5i cohort was higher (53.0 vs. 51.9, p=0.011) and included fewer females (61.5% vs. 74.5%, p<0.0001). Prevalence for some comorbidities was higher with the PDE5is, including: systemic hypertension (60.4% vs. 51.7% , p<0.0001), diabetes (29.2% vs. 21.6%, p<0.0001), renal failure (22.6% vs. 12.1%, p=0.0001), and obesity (20.9% vs. 14.7%, p<0.0012). As PDC increased from 40-59% to ≥ 80%, hospitalizations decreased from 45% to 23% for ERA, and 49% to 28% for PDE-5i. For patients with PDC ≥ 80%, ERA had a lower percent hospitalized (23% vs. 28% ,p=0.02) and fewer hospital admissions (0.4 vs. 0.5, p=0.02) versus PDE-5i. An increase in PDC from 0.50 to 1.00 reduced hospitalization risk by 58% for ERA and 26% for PDE-5i patients. For ERA patients, an increase in adherence had a greater impact on reducing hospitalization risk than PDE-5i (HR=0.549 for PDC, p=0.018 and HR=0.321 for interaction of PDC with ERA therapy, p=0.013) based on a modified Cox hazards model controlling for demographics and baseline comorbidities.


Patients treated with ERAs were younger, had fewer co-morbidities, were more adherent to therapy, and experienced fewer hospitalizations than PDE5i treated patients. This analysis suggests that adherence to PAH therapy was associated with greater risk reduction in hospitalizations for ERA vs. PDE5i. The reason for this difference is unknown. It may reflect differences in patient characteristics. ERA patients may have purer PAH phenotypes (WHO Group 1) for whom adherence has a greater impact on outcomes. These findings suggest that maximizing adherence is an important strategy to ensure the best possible outcomes for PAH patients.