Residual Atherosclerotic Cardiovascular Disease Risk in Statin Users: A Systematic Review and Meta-Analysis

Statins are the cornerstone of lipid-lowering therapy, reducing low-density lipoprotein cholesterol in adults. However, residual atherosclerotic cardiovascular disease (ASCVD) risk among statin users remains unclear. This study estimated residual ASCVD risk in statin users in practice.

We conducted a systematic literature review and meta-analyses following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, including observational studies published January 1, 2013, to August 1, 2023, that reported ASCVD risk in adult statin users. Five outcomes were assessed: composite risk (major adverse cardiovascular events or all-cause death), myocardial infarction, ischemic stroke, cardiovascular-related death, and coronary revascularization. Meta-analysis methods were used to synthesize individual study estimates. For each outcome, forest plots present study-level estimates and the pooled incidence rate per 1000 person-years (PPY).

The meta-analysis of residual composite risk (major adverse cardiovascular events or all-cause death) in the overall population was 12.3 PPY (range, 0.2-72.0). Rates were lower in adults at risk of ASCVD (6.4 PPY [range, 3.7-9.8 PPY]) and higher in adults with prior ASCVD (15.8 PPY [range, 0.2-72.0 PPY]). Meta-analysis for myocardial infarction showed 8.23 PPY (range, 1.1-88.82 PPY) in the overall patient population, and a lower rate of ischemic stroke with a rate of 6.0 PPY (range, 1.4-18.8 PPY). A rate of 4.3 PPY (range, 0.4-22.9 PPY) was estimated for cardiovascular-related death, and 7.4 PPY for coronary revascularization (range, 3.1-27.6 PPY).

Despite substantial between-study variability, this real-world meta-analysis indicates meaningful residual ASCVD risk among statin users, underscoring persistent treatment gaps and need for comprehensive, optimized risk management.