Moderate-intensity statin with ezetimibe vs. high-intensity statin in patients with diabetes and atherosclerotic cardiovascular disease in the RACING trial

Eur Heart J. 2023 Mar 14;44(11):972-983. doi: 10.1093/eurheartj/ehac709.

Abstract

Aims: This study evaluated the effect of moderate-intensity statin with ezetimibe combination therapy vs. high-intensity statin monotherapy among patients with diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD).

Methods and results: This was a pre-specified, stratified subgroup analysis of the DM cohort in the RACING trial. The primary outcome was a 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke. Among total patients, 1398 (37.0%) had DM at baseline. The incidence of the primary outcome was 10.0% and 11.3% among patients with DM randomized to ezetimibe combination therapy vs. high-intensity statin monotherapy (hazard ratio: 0.89; 95% confidence interval: 0.64-1.22; P = 0.460). Intolerance-related discontinuation or dose reduction of the study drug was observed in 5.2% and 8.7% of patients in each group, respectively (P = 0.014). LDL cholesterol levels <70 mg/dL at 1, 2, and 3 years were observed in 81.0%, 83.1%, and 79.9% of patients in the ezetimibe combination therapy group, and 64.1%, 70.2%, and 66.8% of patients in the high-intensity statin monotherapy group (all P < 0.001). In the total population, no significant interactions were found between DM status and therapy regarding primary outcome, intolerance-related discontinuation or dose reduction, and the proportion of patients with LDL cholesterol levels <70 mg/dL.

Conclusion: Ezetimibe combination therapy effects observed in the RACING trial population are preserved among patients with DM. This study supports moderate-intensity statin with ezetimibe combination therapy as a suitable alternative to high-intensity statins if the latter cannot be tolerated, or further reduction in LDL cholesterol is required among patients with DM and ASCVD.

Clinical trial registration: ClinicalTrials.gov, Identifier:NCT03044665.

Keywords: Atherosclerotic cardiovascular disease; Diabetes mellitus; Ezetimibe; Statin.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticholesteremic Agents* / adverse effects
  • Atherosclerosis* / drug therapy
  • Atherosclerosis* / prevention & control
  • Cardiovascular Diseases* / drug therapy
  • Cholesterol, LDL
  • Diabetes Mellitus* / drug therapy
  • Diabetes Mellitus* / epidemiology
  • Drug Therapy, Combination
  • Ezetimibe / therapeutic use
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / adverse effects
  • Treatment Outcome

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Ezetimibe
  • Anticholesteremic Agents
  • Cholesterol, LDL

Associated data

  • ClinicalTrials.gov/NCT03044665