Adherence and Discontinuation of Disease-Specific Therapies for Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis

Background In patients with pulmonary arterial hypertension (PAH), the use of disease-specific therapies (i.e., endothelin receptor antagonists, phosphodiesterase type-5 inhibitors, soluble guanylate cyclase stimulators, prostacyclins, and prostanoids) has been associated with disease improvement and decreased mortality risk. We aimed to quantify the adherence and discontinuation rates for patients prescribed PAH-specific therapies. Methods We performed a systematic review via searching MEDLINE, EMBASE, and the Cochrane Library from their inception to 4 March 2022 for observational studies published in English that reported data on adherence to and persistence with PAH-targeted therapies. Random-effects meta-analysis was performed to explore average adherence and discontinuation rates. Results In all, 14 studies involving 14,861 individuals prescribed PAH-targeted therapies were included. The overall pooled proportion of patients adherent to their PAH-targeted medications was 60.9% (95% confidence interval [CI] 52.3-69.1%). The pooled proportions of patients adherent in questionnaire-based studies and in studies using prescription/dispensing data were 52.9% (95% CI 48.9-56.9%) and 62.9% (95% CI 53.1-72.2%), respectively. The pooled proportion of patients who discontinued their PAH-targeted medications was 42.3% (95% CI 31.6-53.3). Factors reported to impact adherence included administration frequency, length of time on treatment, co-payment, and occurrence of adverse events. Conclusions In the real world, a considerable proportion of patients prescribed PAH-specific therapies were non-adherent or discontinued. As diverse factors may influence treatment adherence, multifaceted interventions are needed to address this trend in order to improve patient outcomes. Registration The systematic review protocol was registered in the PROSPERO database (CRD42022316638).