Adherence to immunosuppression in adult heart transplant recipients: A systematic review

Background: Successful maintenance of a heart transplant (HTx) graft requires adherence to a triple-drug regimen of immunosuppression. However, achieving adequate adherence can be difficult secondary to complicated dosing regimens, side effects, and mental/emotional barriers. A detailed review of current patterns of adherence to immunosuppression in adult HTx recipients is lacking. Objective: This systematic review aims to detail the current landscape of adherence to immunosuppression in adult heart transplant patients, including the measurement of adherence, correlates to adherence, health outcomes associated with nonadherence, as well as strategies to improve adherence in HTx patients. Methods: We conducted searches in PubMed MEDLINE, Embase, CENTRAL register of Controlled Trials (Wiley), and Scopus, from inception to March 2020. Studies were eligible if they outlined an aspect of adherence (as noted above in the objective) to immunosuppression in adult HTx patients. The HTx cohort had to contain at least 10 patients and measurement of adherence had to be done with an objective or otherwise validated measure of adherence (e.g. drug levels, automated pill bottles or adherence questionnaires). Two authors independently screened the articles for inclusion, then subsequently reviewed the full texts of the included articles. Data was extracted into standardized forms and bias evaluations were done using the Newcastle-Ottawa or modified Newcastle-Ottawa tools, depending on the study type. The authors followed all guidelines for the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: The titles/abstracts of 880 articles were reviewed. Ultimately, 23 articles were included in the final review. The median number of participants was 101, with a range of 19 to 1397. Studies provided information on baseline levels of adherence (17 studies), correlates to adherence (14 studies), health outcomes related to nonadherence (3 studies) and interventions to improve adherence (3 studies). Baseline adherence estimates varied greatly depending on the adherence measure. Multiple significant correlates to nonadherence exist and appear to affect patients with certain sociodemographic backgrounds, those with psychological/psychiatric comorbidities and those with poor support structures. Nonadherence is associated with transplant coronary artery disease and acute late rejection; it may also be associated with long-term mortality. Finally, a simplified dosing regimen with once-a-day tacrolimus as well as use of a mobile phone-based intervention were associated with improved adherence. Bias scores were most deficient due to self-reported outcomes in 18 studies, and lack of controls/adjustments for confounders, in 7 studies. Conclusions: Adherence to immunosuppression in transplant patients varies, but is associated with observable and modifiable factors which are worth addressing. Further high-quality studies regarding strategies to improve adherence are needed in the literature.

Automated summary

This systematic review explores the current landscape of adherence to immunosuppression in adult heart transplant patients, highlighting variations in baseline adherence estimates, significant correlates to nonadherence, and potential health outcomes associated with nonadherence. Simplified dosing regimens and mobile phone interventions were found to improve adherence. Further high-quality studies are needed to investigate strategies for improving adherence.