Medication adherence trajectories and clinical outcomes in patients with cardiovascular disease: a systematic review and meta-analysis.

Background: The role of medication adherence trajectories in the clinical outcomes in patients with cardiovascular diseases (CVDs) remains unclear. We aimed to analyse the impact of different medication adherence trajectories on mortality and other key clinical outcomes in patients with CVDs. Methods: We identified longitudinal cohort studies that reported the association between medication adherence trajectories and clinical outcomes in patients with CVDs by conducting a comprehensive search of the Cochrane Library, PubMed, Embase, CINAHL, and Web of Science databases, without applying language restrictions in August 2024. We pooled the published hazard ratios and 95% confidence intervals using random effects models and assessed potential bias through Egger regression analysis. Results: In this meta-analysis, we included nine cohorts with 226 203 patients with a mean age of 66.1 years and a maximum follow-up of five years. Eight of the nine studies used the proportion of days covered to assess medication adherence. We identified four distinct medication adherence trajectories: persistent adherence, persistent nonadherence, gradually increasing adherence, and gradually declining adherence. Compared to persistent adherence, persistent nonadherence was associated with significantly higher risks of all-cause mortality, major adverse cardiovascular events (MACE), and recurrent venous thromboembolism, with risk increases ranging from 32% to nearly three times higher. Gradually increasing adherence was associated with a 26% higher risk of mortality and a 22% increased risk of MACE. In the group with gradually declining adherence, the risk of MACE increased by 24%, while the risk of major bleeding decreased by 43%. The overall risk of bias was low. Sensitivity analyses confirmed the consistency and robustness of these findings. Conclusions: This study underscores the substantial benefits of maintaining persistent adherence to prescribed medication regimens for patients with CVDs. Conversely, persistent nonadherence significantly elevates the risk of adverse clinical outcomes. Registration: PROSPERO: CRD42023456395.