Combination of low- or moderate-intensity statin and ezetimibe vs. high-intensity statin monotherapy on primary prevention of cardiovascular disease and all-cause death: a propensity-matched nationwide cohort study

Eur J Prev Cardiol. 2024 Aug 9;31(10):1205-1213. doi: 10.1093/eurjpc/zwae081.

Abstract

Aims: This study aims to compare the preventive effect of low- or moderate-statin with ezetimibe combination therapy and high-intensity statin monotherapy on cardiovascular disease (CVD) and all-cause death in a real-world setting.

Methods and results: Using the Korean National Health Insurance Service datasets, two cohorts comparing high-intensity statin monotherapy with low- or moderate-intensity statin and ezetimibe combination were constructed by 1:1 propensity score matching procedure. Primary outcome was a composite of myocardial infarction (MI), stroke, and all-cause death. Secondary outcome was an individual event. The study population was followed from baseline until the date of events, or the last health check-ups, whichever came first. Compared to high-intensity statin monotherapy, moderate-intensity statin with ezetimibe combination significantly reduced the risk of composite outcome [hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.77-0.92, P < 0.001] as well as individual MI (HR 0.81, 95% CI 0.71-0.94, P = 0.005) and stroke (HR 0.78, 95% CI 0.65-0.93, P = 0.005), but not all-cause death. Low-intensity statin with ezetimibe also significantly reduced the risk of the composite outcomes (HR 0.80, 95% CI 0.66-0.97, P = 0.024) compared to high-intensity statin monotherapy, but the risk of individual outcome did not differ between two groups. Statin and ezetimibe combination demonstrated consistent effect across various subgroups.

Conclusion: Among people without pre-existing CVD, moderate-intensity statin with ezetimibe combination was superior to high-intensity statin monotherapy in preventing composite outcomes as well as each of MI and stroke. In contrast, low-intensity statin with ezetimibe combination reduced the risk of composite but not individual outcomes.

Keywords: All-cause death; Cardiovascular disease; Ezetimibe; Primary prevention; Statin.

Plain language summary

We compared the preventive effect of low- or moderate-statin with ezetimibe combination and high-intensity statin monotherapy on cardiovascular disease and all-cause death. Low- or moderate-intensity statin with ezetimibe is beneficial for reducing a composite of myocardial infarction (MI), stroke, and all-cause death. Moderate-intensity statin with ezetimibe reduced 19% of MI and 22% of stroke, compared with high-intensity statin. Statin with ezetimibe combination might be attractive bypass for primary prevention, beyond an alternative to high-intensity statin.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Anticholesteremic Agents / administration & dosage
  • Anticholesteremic Agents / therapeutic use
  • Cardiovascular Diseases* / mortality
  • Cardiovascular Diseases* / prevention & control
  • Cause of Death*
  • Databases, Factual
  • Drug Therapy, Combination*
  • Dyslipidemias / blood
  • Dyslipidemias / diagnosis
  • Dyslipidemias / drug therapy
  • Dyslipidemias / epidemiology
  • Dyslipidemias / mortality
  • Ezetimibe* / administration & dosage
  • Ezetimibe* / therapeutic use
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Male
  • Middle Aged
  • Primary Prevention*
  • Propensity Score*
  • Republic of Korea / epidemiology
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Ezetimibe
  • Anticholesteremic Agents