Combining drugs with different mechanisms of action is a way to achieve higher efficacy and safety than with increasing doses of a single agent. 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 of these two approaches is lacking. To address this knowledge gap, a new randomized trial was published in the Lancet on July 18, 2022.
The RACING trial was a randomised, open-label, non-inferiority trial in patients with atherosclerotic cardiovascular disease (ASCVD). The participants 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%.
Between Feb 14, 2017, and Dec 18, 2018, 3780 patients were enrolled at 26 clinical centres in South Korea: 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).
That is, 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.
Reference: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00916-3
