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

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.

Keywords: Dyslipidaemias; Hydroxymethylglutaryl-CoA reductase inhibitors; Percutaneous coronary intervention.

Fig. 1

Study profile for this post-hoc analysis of the RACING trial. RACING, randomised comparison of efficacy and safety of lipid-lowering with statin monotherapy versus statin/ezetimibe combination for high-risk cardiovascular disease; ASCVD, atherosclerotic cardiovascular disease; PCI, percutaneous coronary intervention.

Fig. 2

Time-to-event curves of the primary endpoint according to (A) prior PCI and (B) history of myocardial infarction among patients with prior PCI. Time-to-event curves were plotted using Kaplan–Meier survival analysis. HR, hazard ratio; CI, confidence interval; PCI, percutaneous coronary intervention; MI, myocardial infarction.

Fig. 3

Time-to-event curve of the primary endpoint according to treatment strategy and prior PCI status. Kaplan–Meier survival curves for the primary outcomes among patients (A) with prior PCI, (B) without prior PCI. HR, hazard ratio; CI, confidence interval; PCI, percutaneous coronary intervention.

Fig. 4

Effect of ezetimibe combination therapy on safety endpoint in patients with prior PCI. ∗The incidence of new-onset diabetes mellitus was determined specifically for participants who had no prior history of diabetes mellitus at the time of randomisation. ∗∗Muscle-related adverse events were defined as a composite of rhabdomyolysis, myopathy, myalgia, and myonecrosis. CI, confidence interval. Odds ratios were calculated by the logistic regression analysis in which age, sex, diabetes mellitus, and baseline low-density lipoprotein cholesterol <100 mg/dL were included for adjustment.