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

• Published in: The Lancet (British edition) 2022-07, Vol.400 (10349), p.380-390
• Main Authors: Kim, Byeong-Keuk, Hong, Sung-Jin, Lee, Yong-Joon, Hong, Soon Jun, Yun, Kyeong Ho, Hong, Bum-Kee, Heo, Jung Ho, Rha, Seung-Woon, Cho, Yun-Hyeong, Lee, Seung-Jun, Ahn, Chul-Min, Kim, Jung-Sun, Ko, Young-Guk, Choi, Donghoon, Jang, Yangsoo, Hong, Myeong-Ki
• Format: Article
• Language: English
• Subjects: Anticholesteremic Agents - adverse effects; Arteriosclerosis; Atherosclerosis; Atherosclerosis - drug therapy; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - drug therapy; Cholesterol; Cholesterol, LDL; Clinical outcomes; Clinical trials; Combination therapy; Coronary vessels; Drug dosages; Drug Therapy, Combination; Ezetimibe - adverse effects; Heart failure; Hospitalization; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects; Intolerance; Ischemia; Laboratories; Low density lipoprotein; Patient safety; Patients; Racing; Reduction; Review boards; Rosuvastatin Calcium; Statins; Stroke; Therapy; Treatment Outcome; Vein & artery diseases
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(22)00916-3

Drug combinations rather than increasing doses of one drug can achieve greater efficacy and lower risks. Thus, as an alternative to high-intensity statin monotherapy, moderate-intensity statin with ezetimibe combination therapy can lower LDL cholesterol concentrations effectively while reducing adverse effects. However, evidence from randomised trials to compare long-term clinical outcomes is needed. In this randomised, open-label, non-inferiority trial, patients with atherosclerotic cardiovascular disease (ASCVD) at 26 clinical centres in South Korea were randomly assigned (1:1) to receive either moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 10 mg with ezetimibe 10 mg) or high-intensity statin monotherapy (rosuvastatin 20 mg). The primary endpoint was the 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke, in the intention-to-treat population with a non-inferiority margin of 2·0%. This trial is registered with ClinicalTrials.gov, NCT03044665 and is complete. Between Feb 14, 2017, and Dec 18, 2018, 3780 patients were enrolled: 1894 patients to the combination therapy group and 1886 to the high-intensity statin monotherapy group. The primary endpoint occurred in 172 patients (9·1%) in the combination therapy group and 186 patients (9·9%) in the high-intensity statin monotherapy group (absolute difference -0·78%; 90% CI -2·39 to 0·83). LDL cholesterol concentrations of less than 70 mg/dL at 1, 2, and 3 years were observed in 73%, 75%, and 72% of patients in the combination therapy group, and 55%, 60%, and 58% of patients in the high-intensity statin monotherapy group (all p