Clinical question: Can you use a moderate-intensity statin with ezetimibe combination therapy for very high-risk (VHR) patients with ASCVD?
Background: The ACC/AHA guidelines recommend the use of high-intensity statin therapy for very high-risk patients with ASCVD. However, drug-related adverse effects are one limiting factor leading to its underuse. The RACING trial demonstrated the noninferiority of a moderate-intensity statin with ezetimibe combination therapy compared with high intensity for the 3-year composite cardiovascular outcomes in patients with ASCVD; however, whether the effect is preserved among VHR patients is not known.
Study design: Post hoc analysis of multicenter, randomized, clinical trial
Setting: 26 centers in Korea
Synopsis: Of the 3,780 patients, 1,511 adults had very high-risk ASCVD and were randomly assigned to receive either ezetimibe/moderate-intensity statin combination therapy (rosuvastatin, 10 mg plus ezetimibe, 10 mg) or high-intensity statin monotherapy (rosuvastatin, 20 mg). VHR patients were defined as having a history of multiple major ASCVD events or one major ASCVD event in addition to various high-risk conditions by the 2018 AHA/ACC guidelines. The primary endpoint was the occurrence of cardiovascular death, coronary or peripheral revascularization, hospitalization for cardiovascular events, or nonfatal stroke within three years after randomization. This study showed that there was no significant difference in the primary endpoint between the combination therapy and high-intensity statin monotherapy groups for both VHR patients (85 of 757 [11.2%] versus 88 of 754 [11.7%]; HR, 0.96; 95% CI, 0.71 to 1.30) and non-VHR patients (87 of 1,137 [7.7%] versus 98 of 1,132 [8.7%]; HR, 0.88; 95% CI, 0.66 to 1.18) without statistical heterogeneity (P for interaction =.67). There was no evidence for heterogeneity of the treatment effect between VHR and non-VHR patients (P for interaction =.67), but a lack of statistical power limits drawing definitive conclusions about the absence of differential effects.
Bottom line: For VHR patients with ASCVD a moderate-intensity statin with ezetimibe combination therapy was comparable to high-intensity statin monotherapy in terms of a three-year primary endpoint and was associated with lower drug intolerance, greater LDL-C level reduction, and achievement of LDL-C level less than 70 mg/dL.
Citation: Lee SJ, et al. Moderate-intensity statin with ezetimibe combination therapy vs high-intensity statin monotherapy in patients at very high risk of atherosclerotic cardiovascular disease: A post hoc analysis from the RACING randomized clinical trial. JAMA Cardiol. 2023;8(9):853-8. Erratum in: JAMA Cardiol. 2023;8(9):891.
Dr. Rinaldi
Dr. Rinaldi is a hospitalist at Atrium Health Wake Forest Baptist, and an assistant professor in internal medicine at Wake Forest University School of Medicine, both in Winston-Salem, N.C.