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

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Abstract

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).

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Author notes

  1. Abdallah Y. Naser and Richard Ofori-Asenso contributed equally to this work.

Authors and Affiliations

  1. Department of Applied Pharmaceutical Sciences and Clinical Pharmacy, Faculty of Pharmacy, Isra University, Amman, Jordan

    Sami Qadus & Abdallah Y. Naser

  2. School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, VIC, 3004, Australia

    Richard Ofori-Asenso, Zanfina Ademi & Danny Liew

  3. Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia

    Zanfina Ademi

  4. Department of Basic Pharmaceutical Sciences, Isra University, Amman, Jordan

    Safaa Al Awawdeh

  5. The Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia

    Danny Liew

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  1. Sami Qadus
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Correspondence to Richard Ofori-Asenso.

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Author contributions

AYN and RO-A conceptualised the study. SQ, AYN, SAA, and RO-A collected the data. All the authors participated in the drafting of this manuscript and provided final approval of the submitted version of the article.

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No funding or sponsorship was received for this study or publication of this article.

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Richard Ofori-Asenso is a current employee of AstraZeneca Plc. The views expressed in this article are his own and do not represent that of his employers. Sami Qadus, Abdallah Y. Naser, Zanfina Ademi, Safaa Al Awawdeh, and Danny Liew declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Qadus, S., Naser, A.Y., Ofori-Asenso, R. et al. Adherence and Discontinuation of Disease-Specific Therapies for Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis. Am J Cardiovasc Drugs 23, 19–33 (2023). https://doi.org/10.1007/s40256-022-00553-6

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