Interventions to manage intolerance among patients prescribed statins for primary prevention of cardiovascular diseases: A systematic review and meta-analysis

The objective of this systematic review and meta-analysis was to identify the interventions used to manage intolerance in patients receiving statins for primary prevention of CVD and to determine the effectiveness of these interventions. This study was conducted according to the PRISMA checklist. The electronic databases MEDLINE (PubMed), SCOPUS, EMBASE, and CINAHL were searched for studies published until June 2025. Based on the NLA definition of statin intolerance, the outcomes were split into adverse effects caused by statins and statin discontinuation. In total, 1,238 studies were identified and screened. Nine studies were eligible for systematic review, and six studies were eligible for meta-analysis. The identified intervention strategies were adjuvant therapy, statin titration, replacing statins with other lipid-lowering agents and switching to different statin. The meta-analysis showed that the pooled risk ratio (RR) relative to control was 0.97 (95% CI, 0.86-1.08) in randomized controlled trials and 0.94 (95% CI, 0.63-1.42) in overall, with point estimates in favour of intervention arms. Moderate to substantial heterogeneity was observed, with I2 between 27% to 57%. Due to the smaller number of studies, no clear conclusions can be drawn regarding how the implemented interventions may affect statin discontinuation. This study showed no strong evidence that the implemented interventions reduced statin intolerance. PROSPERO registration numberCRD42024587573 HighlightsThis study found that the intervention strategies used to manage intolerance in patients receiving statins for the primary prevention of cardiovascular diseases were adjuvant therapy, statin titration, replacing statins with other lipid-lowering agents and switching to different statin. O_LIThis study showed no strong evidence that the implemented interventions reduced statin intolerance C_LIO_LIDue to the smaller number of studies, no clear conclusions can be drawn regarding how the implemented interventions may affect statin discontinuation C_LI