Medication Non-Adherence in Patients with Pulmonary Arterial Hypertension: The Pulmonary Hypertension Association Registry (PHAR).

Rationale Pulmonary arterial hypertension (PAH) is associated with significant morbidity and mortality. The extent of medication non-adherence in PAH is uncertain and may be linked to adverse outcomes. There has been a lack of multi-center, registry-based studies assessing medication non-adherence and patient-centered outcomes in PAH. Objectives To determine the incidence of self-reported non-adherence in Pulmonary Hypertension Association Registry (PHAR) participants with PAH or chronic thromboembolic pulmonary hypertension (CTEPH) and the relationship of non-adherence with several patient-centered outcomes (mortality, hospitalization rates, emergency department [ED] visits, and health-related quality of life [HRQoL]). Methods Self-reported PAH medication non-adherence was captured at PHAR enrollment and during follow-up visits. Predictors of non-adherence were modeled using generalized estimating equations (GEEs) assuming a binary distribution. Outcomes associated with non-adherence were modeled using GEEs with a Poisson distribution. Results A total of 1543 patients were included, of whom 1092 (70.8%) were female and 1340 (86.8%) had PAH. The overall rate of any self-reported non-adherence was 6.1% (95% confidence interval (CI) [5.3, 6.9]). Predictors of non-adherence included self-reported male sex (odds ratio (OR) 1.4; 95% CI [1.0, 1.9]; p = 0.02), poverty (OR 1.6; 95% CI [1.2, 2.3]; p = 0.01), not being partnered (OR 1.5; 95% CI [1.1, 1.9]; p = 0.01), having Medicaid or no health insurance (OR 2.1; 95% CI [1.5, 2.9]; p < 0.001), and having completed high school but not having a college degree (OR 1.7; 95% CI [1.1, 2.9]; p < 0.001). PHAR participants who reported any non-adherence had 50.0% more ED visits (p < 0.001), 13.3% more hospital admissions (p = 0.03), and 61.9% more days hospitalized (p = 0.01). No relationship was observed between non-adherence and type or number of PAH therapies or all-cause mortality. Participants reporting non-adherence had worse mean SF-12 scores (p < 0.001) and worse emPHasis-10 scores (p = 0.02). Conclusions The rate of self-reported non-adherence in PHAR registrants was low but was associated with male sex and several social determinants of health. While complexity or type of PAH regimen did not appear to influence non-adherence, non-adherence was associated with numerous adverse patient-centered outcomes, including higher healthcare utilization and worse HRQoL. Due to limitations in the structure of the gathered data, relationships between exposure and outcomes were not temporally definitive; these observations warrant additional prospective studies.