Adherence to statins and development of atherosclerosis-related events. A systematic review and meta-analysis

Adherence to lipid-lowering treatment (LLT) is of paramount importance for the prevention of atherosclerosis-related events (ASCVD). The threshold for someone to be adherent is ≥80 % of the total prescribed medication. We conducted a meta-analysis to assess how adherence to LLT affects the development of ASCVD.

We searched PubMed (up to February 2025) for randomized controlled trials, cohorts and nested case control studies that assessed adherence to LLT. We performed random effects meta-analysis with primary outcome the development of ASCVD based on the level of adherence to LLT.

We included 66 articles corresponding to 3,345,718 individuals. All studies evaluated statins as LLT. Good vs. poor statin adherence reduced by 35 % the risk for all-cause mortality (RR:0.65; 95%CI: 0.56-0.76; I² = 98 %), 24 % for any cardiovascular (CV) event (RR:0.76; 95%CI: 0.72-0.80; I² = 90 %), 30 % for myocardial infarction (MI) (RR:0.70; 95%CI: 0.62-0.80; I² = 90 %) and 32 % for stroke (RR:0.68; 95%CI: 0.58-0.79; I² = 81 %). For participants without established ASCVD, statin adherence reduced by 32 % the risk for any CV event (RR:0.68; 95%CI: 0.46-1.00; I² = 97 %). For those with established ASCVD, statin adherence reduced by 25 % the risk for any CV event (RR:0.75; 95%CI: 0.64-0.88; I² = 64 %), 51 % for MI (RR:0.49; 95%CI: 0.32-0.73; I² = 80 %) and 50 % for stroke (RR:0.50; 95%CI: 0.26-0.97; I² = 87 %). Statin discontinuation increased by 90 % the mortality risk (RR:1.90; 95%CI: 1.33-2.71; I² = 87 %). Even good vs. intermediate adherence (40 %-79 %) decreased by 32 % the risk for any CV event (RR:0.68; 95%CI: 0.60-0.76; I² = 94 %). Sensitivity analyses including studies with different than the standard (≥80 %) threshold did not differ from the main results.

Statin adherence is of paramount importance to reduce ASCVD risk and mortality. Understanding adherence patterns or barriers and ensuring consistent adherence to LLT by tailored interventions should be a key priority in clinical practice and healthcare policies.