DOI: 10.1161/jaha.125.044840 ISSN: 2047-9980

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

Alexandre H. Watanabe, Lori D. Bash, Tracy Westley, Andrea Garcia, Emily Aiello, Jasmine Bradbury, Jyoti Garg, Vyshnavi Telukuntla, Michael G. Nanna

Background

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.

Methods

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).

Results

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).

Conclusions

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.

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