Adherence to Lipid‐Lowering Therapies and Cardiovascular Outcomes in Patients With Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta‐Analysis

Persistently elevated low-density lipoprotein cholesterol is a major risk factor for atherosclerotic cardiovascular disease (ASCVD). Despite the availability of lipid-lowering therapy (LLT), most patients with ASCVD do not achieve guideline-recommended low-density lipoprotein cholesterol goals. Poor adherence to LLT is a key barrier to low-density lipoprotein cholesterol lowering and may be associated with adverse cardiovascular outcomes. We conducted a systematic review and meta-analysis to clarify the relationship between adherence to LLT and cardiovascular outcomes in patients with ASCVD. Systematic searches of PubMed, Embase, Scopus, and Cumulative Index to Nursing and Allied Health Literature were performed in March 2023 (updated September 2024). Observational studies in adults with clinical ASCVD reporting objective measures of adherence or persistence to LLT and cardiovascular outcomes, including death, cardiovascular death, and major adverse cardiovascular events, were included. Risk of bias was assessed using the Clinical Advances Through Research and Information Translation tool. Of 12 466 unique records identified, 39 met the inclusion criteria. Most studies only reported adherence to statins (33/39), and most measured adherence using proportion of days covered (25/39). Using an adherence threshold of ≥80%, adherence to LLT was shown to statistically significantly reduce risk of death (hazard ratio HR, 0.56 95% CI, 0.34-0.92; P=0.0268; I2 95%), major adverse cardiovascular events (HR, 0.77 95% CI, 0.68-0.86; P=0.0007; I2 83%), myocardial infarction (HR, 0.86 95% CI, 0.79-0.95; P=0.0147; I2 0%), and non-statistically significant reductions in cardiovascular death (HR, 0.44 95% CI, 0.12-1.60; P=0.1528; I2 92%) and ischemic stroke (HR, 0.83 95% CI, 0.58-1.18; P=0.1856; I2 52%). In this systematic review and meta-analysis, adherence to LLT was associated with reduced risk of cardiovascular events in patients with clinical ASCVD. URL: https://www.crd.york.ac.uk/prospero/; identifier: CRD42023427146.