Ezetimibe–moderate-intensity statin combo viable for people at very high-risk of ASCVD

In the treatment of individuals at very high risk (VHR) of atherosclerotic cardiovascular disease (ASCVD), the use of the combination of ezetimibe plus moderate-intensity statin yields similar protective effects as high-intensity statin monotherapy, according to a post hoc analysis of the RACING* trial.

The open-label trial included 3,780 participants (mean age 64 years, 75 percent men), among whom 1,511 (40.0 percent) had very high-risk ASCVD, defined according to the 2018 American Heart Association/American College of Cardiology guidelines. This very high-risk category was associated with a higher frequency of the primary endpoint of the 3-year outcome of cardiovascular death, coronary or peripheral revascularization, hospitalization of cardiovascular events, or nonfatal stroke (hazard ratio [HR], 1.42, 95 percent confidence interval [CI], 1.15–1.75).

The participants were randomly assigned to receive moderate-intensity statin (rosuvastatin 10 mg) plus ezetimibe (10 mg) or high-intensity statin monotherapy (rosuvastatin 20 mg). The primary endpoint did not significantly differ between the combination and monotherapy treatment groups among participants in the very-high-risk (VHR) category (11.2 percent vs 11.7 percent; HR, 0.96, 95 percent CI, 0.71–1.30) and among those in the non-very-high-risk (non-VHR) category (7.7 percent vs 8.7 percent; HR, 0.88, 95 percent CI, 0.66–1.18).

Meanwhile, combination therapy led to a significantly lower median low-density lipoprotein cholesterol (LDL-C) level at year 1 compared with high-intensity statin monotherapy both in the VHR group (57 vs 65 mg/dL) and the non-VHR group (58 vs 68 mg/dL; p<0.001 for both).

Both the VHR and non-VHR groups achieved a significantly greater mean change in LDL-C level with combination therapy than with monotherapy, both at year 1 (VHR: −19.1 vs −10.1 mg/dL; non-VHR: −23.7 vs −12.5 mg/dL), year 2 (VHR: −22.3 vs −13.0 mg/dL; non-VHR: −25.2 mg/dL vs −15.1 mg/dL), and year 3 (VHR: −18.8 vs −9.7 mg/dL; non-VHR: −23.5 vs −12.6 mg/dL; p<0.001 for all).

The proportion of patients with LDL-C level <70 mg/dL at 1 year was 73 percent among participants who received combination therapy and 58 percent among those who received high-intensity statin monotherapy in the VHR group, and 72 percent and 53 percent in the non-VHR group, respectively (p<0.001 for both).

Finally, combination therapy led to less frequent discontinuation or dose reduction of the lipid-lowering drug due to intolerance compared with high-intensity statin monotherapy in both the VHR group (4.6 percent vs 7.7 percent; p=0.02) and non-VHR group (5.0 percent vs 8.7 percent; p=0.001).