A randomized, open-label, noninferiority trial published in The Lancet found that moderate-intensity statin combined with ezetimibe was noninferior to high-intensity statin monotherapy among patients with atherosclerotic cardiovascular disease (ASCVD).

This study (ClinicalTrials.gov Identifier: NCT03044665) was conducted at 26 sites in South Korea between 2017 and 2018. Patients (N=3780) with ASCVD who required high-intensity statin therapy to achieve low-density lipoprotein cholesterol (LDL-C) levels of 70 mg/dL or less and who had a previous cardiovascular event were randomly assigned in a 1:1 ratio to receive 10 mg ezetimibe plus 10 mg rosuvastatin (n=1894) or 20 mg rosuvastatin (n=1886) once daily for 3 years. Patients were monitored for LDL-C and major cardiovascular outcomes at 2 and 6 months and yearly thereafter.

Both cohorts were 25% women and were aged mean 64±10 years, and 66% of both cohorts had a previous percutaneous coronary intervention and a medium serum LDL-C concentration of 80 (IQR, 64-100) mg/dL. In the moderate- and high-intensity cohorts BMI was 25.0±3.2 and 25.1±3.1; 39% and 40% had a previous myocardial infarction; 66% and 68% had hypertension; and 17% and 16% were current smokers, respectively.


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The composite primary endpoint of cardiovascular death, major cardiovascular event, or nonfatal stroke occurred among 9.1% of the moderate-intensity and 9.9% of the high-intensity recipients (hazard ratio [HR], 0.92; 95% CI, 0.75-1.13; P =.43). The composite secondary endpoint of all-cause mortality, major cardiovascular event, or nonfatal stroke occurred among 9.8% and 10.4% of the moderate- and high-intensity cohorts (HR, 0.94; 95% CI, 0.77-1.15; P =.94), respectively.

Stratified by individual endpoints, no significant group differences were observed.

The number of participants in the moderate-intensity cohort that achieved an LDL-C concentration of less than 70 mg/dL was 73% at year 1, 75% at year 2, and 72% at year 3 compared with 55%, 60%, and 58% among the high-intensity cohort, respectively.

A total of 4.8% of the moderate-intensity and 8.2% of the high-intensity treatment recipients discontinued or had a dose reduction due to intolerance. The moderate- and high-intensity recipients reported dizziness or weakness (n=10 vs n=21), myalgia (n=7 vs n=22), chest discomfort or headache (n=7 vs n=12), urticaria or itching (n=6 vs n=7), and gastrointestinal symptoms (n=4 vs n=9), respectively. Deaths occurred among 1.4% of the moderate- and 1.2% of the high-intensity cohorts.

In a subgroup analysis, neither therapy was preferred for any group.

The major limitation of this study is the open-label design.

“…moderate-intensity statin with ezetimibe combination therapy was noninferior to high-intensity statin monotherapy in terms of a 3-year composite of cardiovascular death, major cardiovascular events, or nonfatal stroke with a higher proportion of patients who achieved LDL cholesterol concentration of less than 70 mg/dL and lower drug discontinuation or dose reduction owing to intolerance,” the study authors wrote.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Kim B-K, Hong S-J, Lee Y-J, et al. Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING): a randomised, open-label, non-inferiority trial. Lancet. Published online July 18, 2022. doi:10.1016/S0140-6736(22)00916-3