Interaction Between Statin Use, Coronary Artery Disease Phenotypes, on Computed Tomography Angiography, and Cardiovascular Outcomes

JACC Cardiovasc Imaging. 2025 Oct;18(10):1116-1127. doi: 10.1016/j.jcmg.2025.05.018. Epub 2025 Aug 5.

Abstract

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.

Keywords: coronary CTA; coronary artery disease; prognosis; statin therapy.

MeSH terms

  • Aged
  • Computed Tomography Angiography*
  • Coronary Angiography*
  • Coronary Artery Disease* / diagnostic imaging
  • Coronary Artery Disease* / drug therapy
  • Coronary Artery Disease* / mortality
  • Coronary Artery Disease* / therapy
  • Dyslipidemias* / diagnosis
  • Dyslipidemias* / drug therapy
  • Dyslipidemias* / mortality
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Male
  • Middle Aged
  • Phenotype
  • Predictive Value of Tests
  • Protective Factors
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors