Background: Although statins are recommended for decreasing cardiovascular risk, their efficacy across different patient phenotypes stratified by coronary artery disease (CAD) remains unclear.
Objectives: This study aims to evaluate whether statins decrease major adverse cardiac events (MACE) among CAD phenotypes according to severity, vulnerability and extent categorized by coronary computed tomography angiography (CTA).
Methods: The authors analyzed consecutive patients who were referred for coronary CTA at a tertiary center for the assessment of chronic coronary syndrome. The primary endpoint was MACE defined as a composite of all-cause mortality, acute myocardial infarction, or revascularization for unstable angina. Statin use was defined as annualized days on statin therapy (days on statin based on redeemed prescriptions, divided by follow-up time), and analyzed for each 10% increase in statin use over the follow-up period. Interaction analysis, adjusting for risk factors was applied to define treatment benefit across CAD phenotypes.
Results: Overall, 11,026 individuals (mean age: 58.6 ± 11.9 years, 54.7% male) were analyzed who underwent coronary CTA between January 1, 2013, and December 31, 2020. A 10% increase in statin use was associated with lower risk for MACE the stratified Cox-regression model in patients with CAD (adjusted HR [aHR]: 0.95 [95% CI: 0.92-0.99]; P = 0.006), but not in patients without CAD (aHR: 0.95 [95% CI: 0.84-1.07]; P = 0.370). In the total population using interaction analysis including CAD phenotypes, a 10% increase in statin use decreased the risk for MACE in the presence of obstructive CAD (aHR: 0.91 [95% CI: 0.85-0.97]; P = 0.006), high-risk plaque (aHR: 0.82 [95% CI: 0.68-0.98]; P = 0.026), calcium score of ≥400 (aHR: 0.93 [95% CI: 0.87-0.99]; P = 0.024), and segment involvement score of >4 (aHR: 0.89 [95% CI: 0.84-0.95]; P < 0.001), but not for any CAD (aHR: 0.95 [95% CI: 0.85-1.07]; P = 0.411).
Conclusions: Statin efficacy to decrease MACE depends on CAD phenotypes and increases with the extent and severity of disease and in the presence of high-risk plaques. Patients without CAD have no benefit from statin therapy regarding MACE. Coronary CTA may play a pivotal role in optimizing statin allocation for personalized treatment decisions to prevent MACE.
Editors
Editor-in-Chief
Y.S. Chandrashekhar, MD, DM, FACC
CME Editor
Kenneth A. Ellenbogen, MD
Authors
Bálint Szilveszter, MD, PhD
Important Dates
Date of Release: October 6, 2025
Term of Approval/Date of CME/MOC Expiration: October 5, 2026