Interventions to improve statin adherence showed modest effects across study designs in primary prevention of cardiovascular disease (CVD). This systematic review and meta-analysis, conducted according to PRISMA guidelines and registered in PROSPERO (CRD42024587573), and published in European Journal of Preventive Cardiology, assessed interventions aimed at improving adherence to statin therapy for primary prevention of CVD. Literature searches were performed across MEDLINE (PubMed), SCOPUS, EMBASE, and CINAHL for studies published between January 2000 and May 2024.

A total of 34 studies met eligibility criteria, including 18 non-cluster randomized controlled trials (ncRCTs), 10 cluster randomized controlled trials (cRCTs), and 6 non-randomized studies of interventions (NRSIs). Interventions were grouped into five categories: multifaceted approaches, education-based strategies, behavior change/monitoring interventions, regimen modification, and incentive-based approaches.

Meta-analysis showed that, compared with control groups, point estimates favored intervention arms, although effect sizes were modest. The pooled risk ratio (RR) was 1.12 (95% CI, 1.00-1.25) for ncRCTs, 1.50 (95% CI, 0.97-2.31) for cRCTs, and 1.37 (95% CI, 0.95-1.98) for NRSIs. Substantial heterogeneity was observed across studies (I² >91%), limiting certainty in effect estimates. Subgroup analyses showed point estimates favoring digital components (ncRCTs RR, 1.08; 95% CI, 1.03-1.12; cRCTs RR, 1.30; 95% CI, 1.07-1.59), as well as education-based (RR, 1.05; 95% CI, 1.02-1.09) and multifaceted interventions (RR, 1.11; 95% CI, 1.07-1.16) in ncRCTs. Interventions were associated with lower low-density lipoprotein cholesterol (LDL-C) levels, with less consistent effects on total cholesterol (TC).

Interventions were associated with modest improvements in statin adherence, with small effect sizes and limited certainty.