Research Article: High rates of medication adherence in patients with pulmonary arterial hypertension: An integrated specialty pharmacy approach

Date Published: June 6, 2019

Publisher: Public Library of Science

Author(s): Nisha B. Shah, Rhonita E. Mitchell, Stephanie Terry Proctor, Leena Choi, Joshua DeClercq, Jacob A. Jolly, Anna R. Hemnes, Autumn D. Zuckerman, Yoshihiro Fukumoto.


Phosphodiesterase-5 inhibitors (PDE-5I) have demonstrated improvement in disease symptoms and quality of life for patients with pulmonary arterial hypertension (PAH). Despite these benefits, reported adherence to PDE-5I therapy is sub-optimal. Clinical pharmacists at an integrated practice site are in a unique position to mitigate barriers related to PAH therapy including medication adherence and costs. The primary objective of this study was to assess medication adherence to PDE-5I therapy within an integrated care model at an academic institution. The secondary objective was to assess the impact of out-of-pocket (OOP) cost, frequency of dosing, adverse events (AE) and PAH-related hospitalizations on medication adherence. We performed a retrospective cohort analysis of adult patients with PAH who were prescribed PDE-5I therapy by the center’s outpatient pulmonary clinic and who received medication management through the center’s specialty pharmacy. We defined optimal medication adherence as proportion of days covered (PDC) ≥ 80%. Clinical data including AEs and PAH-related hospitalizations were extracted from the electronic medical record, and financial data from pharmacy claims. Of the 131 patients meeting inclusion criteria, 94% achieved optimal adherence of ≥ 80% PDC. In this study population, 47% of patients experienced an AE and 27% had at least one hospitalization. The median monthly OOP cost was $0.62. Patients with PDC<80% were more likely to report an AE compared to patients with PDC≥ 80% (p = 0.002). Hospitalization, OOP cost, and frequency of dosing were not associated with adherence in this cohort. Patients receiving PDE-5I therapy through an integrated model achieved high adherence rates and low OOP costs.

Partial Text

Pulmonary hypertension (PH) is a chronic, progressive disease characterized by elevated pulmonary vascular pressure.[1] Pulmonary arterial hypertension (PAH) is a subgroup of PH characterized by pre-capillary PH. [2] Symptoms of PH are typically non-specific and may include shortness of breath, fatigue, angina and weakness. [3]

We conducted a retrospective cohort analysis of patients with WHO Group 1 PAH prescribed a PDE-5I (sildenafil or tadalafil) by the center’s outpatient pulmonary clinic who received medication management through the center’s specialty pharmacy. Patients with less than three prescription claims during the study period were excluded given that measurement of adherence over a short period of time may lead to inaccuracy and at least three dispenses are recommended for a meaningful adherence calculation.[14] The study period was from January 1, 2014 through December 31, 2016. This time period was selected as specialty pharmacist integration occurred in 2014 and significantly impacted the clinic care model. We extracted data from specialty pharmacy claims and electronic medical records (EMR) of patients who met inclusion criteria. This study was reviewed and approved by the Vanderbilt Institutional Review Board (IRB# 170513) as an exempt study under 45 CFR 46.101 (b)(4). Data was managed using Research Electronic Data Capture (REDCap) hosted at Vanderbilt University.[15] Please refer to the S1 Table to view the specific data variables collected and analyzed.

Of the 180 patients screened, we excluded 18 patients due to having less than three prescription claims through the specialty pharmacy. We excluded an additional 30 patients due to lack of a WHO Group 1 PAH diagnosis. We excluded one patient post-evaluation due to multiple pharmacy changes during study period, which made an accurate medication adherence calculation not feasible (see Fig 1). Therefore, 131 patients were included for analysis. Of the total study cohort, 70% were female and 78% were Caucasian. Median age was 55 years (IQR: 45–62 years). More than half (62%) of the population were non-smokers and 71% had government-funded insurance. Of the 131 patients, the majority were in functional class II or III (89%; see Table 1). Half of the patients were receiving one concomitant therapy and 19% of patients were receiving two concomitant therapies.

Patients receiving care within the high-touch, integrated VSP model maintained high rates of medication adherence over a two-year period. Furthermore, previous predictors of low medication adherence such as increased dosing frequency and medication cost did not have a negative impact on adherence in this cohort.