1. 3-year composite outcome of stroke and cardiovascular disease was comparable between both groups (9.1% combination vs. 9.9% monotherapy).
2. Combination therapy was non-inferior to statin monotherapy for proportion of patients achieving an LDL <70 mg/dL at 3 years.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Current guidelines suggest aggressive treatment with increased statin dose in patients with atherosclerotic cardiovascular disease. However, new evidence suggests that combination therapy, as opposed to high-dose monotherapy, may be equally effective. This randomized controlled trial aimed to compare the safety and efficacy of moderate-intensity statin plus ezetimibe (both 10 mg) versus high-dose statin monotherapy, rosuvastatin (20 mg), in patients with cardiovascular disease. Primary outcome was the composite score of cardiovascular death, major cardiovascular events, or non-fatal stroke, assessed annually for three years. Key secondary outcomes included patients with LDL cholesterol < 70 mg/dL and discontinuation or dose reduction of study drug due to intolerance. According to study results, combination therapy was noninferior to statin monotherapy for the primary outcome. A significantly greater proportion of patients in the combination group achieved an LDL cholesterol concentration less than 60 mg/dL in the combination group. A major strength of this study is that it followed patients longitudinally with low attrition.
Relevant Reading: Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes
In-depth [randomized-controlled trial]: Between Feb 14, 2017, and Dec 18, 2018, 3780 patients were enrolled across 26 sites in South Korea. Patients were followed annually for 3 years. Altogether, 3780 patients (1894 in statin plus ezetimibe and 1886 in statin monotherapy) were included in the intention-to-treat analysis. The primary outcome of cardiovascular death, related events, or stroke was comparable in both groups (9.1% in combination therapy vs. 9.9% in statin monotherapy, 90% confidence interval [CI] -2.39 to 0.83). However, a greater proportion of patients achieved LDL cholesterol < 70 mg/dL at 1, 2, and 3 years in the combination therapy group compared to statin monotherapy (73%, 75%, and 72% vs. 55%, 60%, and 58%, respectively, p<0.0001). In contrast, there were fewer instances of drug intolerance in combination therapy compared to statin monotherapy (4.8% vs. 8.2%, p<0.0001). Overall, findings from this study suggest that combination therapy of statin and ezetimibe may be non-inferior to statin monotherapy alone.
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