Journal Article

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

Kim, Byeong-Keuk, Lee, Seung-Jun, Hong, Soon Jun, Choi, Donghoon, Hong, Myeong-Ki, Ko, Young-Guk, Rha, Seung-Woon, Lee, Yong-Joon, Kim, Jung-Sun, Hong, Sung-Jin, Yun, Kyeong Ho, Hong, Bum-Kee, Jang, Yangsoo, Ahn, Chul-Min, Heo, Jung Ho, Cho, Yun-Hyeong

2022

Overview

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<0·0001). Discontinuation or dose reduction of the study drug by intolerance was observed in 88 patients (4·8%) and 150 patients (8·2%), respectively (p<0·0001). Among patients with ASCVD, moderate-intensity statin with ezetimibe combination therapy was non-inferior to high-intensity statin monotherapy for the 3-year composite outcomes with a higher proportion of patients with LDL cholesterol concentrations of less than 70 mg/dL and lower intolerance-related drug discontinuation or dose reduction. Hanmi Pharmaceutical.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: 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