Efficacy and safety of moderate-intensity statin with ezetimibe combination therapy in patients after percutaneous coronary intervention: a post-hoc analysis of the RACING trial
Jong‐Il Park, Seung‐Jun Lee, Bum‐Kee Hong, Yun‐Hyeong Cho, Won‐Yong Shin, Sangwook Lim, Woong-Chol Kang, Yongwhi Park, Sung-Yoon Lee, Yong‐Joon Lee, Sung‐Jin Hong, Chul‐Min Ahn, Byeong‐Keuk Kim, Young‐Guk Ko, Donghoon Choi, Myeong‐Ki Hong, Yangsoo Jang, Jung‐Sun Kim, Jong‐Il Park, Seung‐Jun Lee, Yong‐Joon Lee, Sung‐Jin Hong, Chul‐Min Ahn, Byeong‐Keuk Kim, Young‐Guk Ko, Donghoon Choi, Myeong‐Ki Hong, Jung‐Sun Kim, Bum‐Kee Hong, Jung-Hee Lee, Ung Kim, Yun‐Hyeong Cho, Won‐Yong Shin, Sang-Wook Yangsoo Lim Jang, Woong-Chol Kang, Yongwhi Young Hoon Park Jung, Sung-Yoon Lee, Kyoung Jin Kim, Soon Jun Hong, Kyeong Ho Yun, Jung Ho Heo, Seung‐Woon Rha, Woong Choi, Wang Soo Lee, Jinok Jung, Sunghoon Choi, Youn Haeng Cho, Woo Jung Park, Changhwan Youn, Seung‐Ho Hur, Hyun Hee Choi, Ju Han Kim, Hyun Kuk Kim, Yujung Choi
Abstract
Background: Moderate-intensity statin role with ezetimibe combination therapy following percutaneous coronary intervention (PCI) has not been thoroughly investigated, particularly compared to high-intensity statin monotherapy. We aimed to investigate the effect of ezetimibe combination with moderate-intensity statin in patients with atherosclerotic cardiovascular disease following PCI. Methods: This was a post-hoc analysis of a subset of patients who underwent PCI in the RACING trial. At 26 centres in South Korea, patients with atherosclerotic cardiovascular disease (ASCVD) were randomly assigned 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 prespecified endpoints of the RACING trial were used. The primary endpoint was the 3-year composite of cardiovascular death, major cardiovascular events, and nonfatal stroke. Event rates between the two groups were compared using log-rank tests, and hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox regression analysis. Consistent with the RACING trial, the primary and secondary efficacy endpoints were evaluated using an intention-to-treatment approach, and the safety endpoints were assessed in the safety population. The RACING trial was registered at ClinicalTrials.gov (NCT03044665). Findings: Between Feb 14, 2017, and Dec 18, 2018, 3780 participants were enrolled in the RACING trial. Prior history of PCI was found in 2497 patients (67%, median 64 years, 79% male), and was associated with higher rates of the primary endpoint (hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.06-1.69; p = 0.014). Among patients with prior PCI, moderate-intensity statin therapy with ezetimibe combination versus high-intensity statin therapy did not increase the risk of the primary endpoint (HR, 0.95; 95% CI, 0.74-1.24; p = 0.781). The proportion of patients with low-density lipoprotein cholesterol (LDL-C) <70 mg/dL at 1, 2, and 3 years was 74%, 76%, and 73%, respectively, in the combination therapy group, and was significantly higher than that in the high-intensity statin monotherapy group (57%, 62%, and 59%, respectively, all p < 0.001). Discontinuation of lipid-lowering drugs occurred less frequently in the combination group (4.2% vs. 7.6%, p = 0.001). Interpretation: The effects of ezetimibe combination therapy observed in the RACING trial were consistently preserved among patients with ASCVD following PCI. Ezetimibe combination could be considered as a suitable therapeutic strategy to achieve strict control of LDL-C and reduce drug intolerance in patients who underwent PCI. Funding: Hanmi Pharmaceutical, Seoul, South Korea.