Efficacy and metabolic impact of combination therapy vs. high-intensity statin monotherapy: an exploratory analysis of the Save SAMS Trial

Background Ezetimibe, in combination with statins, is essential for LDL cholesterol reduction. Albeit current guidelines prioritize statins as the first-line therapy, studies indicate that moderate-intensity statin plus ezetimibe provides clinical outcomes comparable to high-intensity statin monotherapy. Additionally, in elderly patients, combination therapy may lower the incidence of statin-associated muscle symptoms (SAMS). This study is an exploratory analysis of the Save SAMS trial, assessing the efficacy of combination therapy with potency comparable to high-intensity statins. Methods The Save SAMS trial included patients aged 70 years or older with atherosclerotic cardiovascular disease (ASCVD), with a total of 561 patients analyzed. In this study, we included 322 patients for whom baseline and 6-month measurements of lipid battery, lipoprotein (a), fasting glucose, insulin, and HOMA-IR were available. Results A total of 322 older patients were divided into two groups according to randomization. There were no significant differences in baseline characteristics. In terms of lipid profile, the combination therapy exhibited similar potency to high-intensity statin monotherapy in reducing total cholesterol, triglycerides, and LDL cholesterol. However, in the high-intensity statin monotherapy group, lipoprotein (a), insulin levels, and HOMA-IR significantly increased at 6 months, whereas no significant changes were observed in the combination therapy group. Conclusion Combination therapy, with LDL-lowering efficacy comparable to that of high-intensity statin monotherapy, also demonstrated similar potency in reducing total cholesterol and triglycerides in older patient with ASCVD. Furthermore, it showed advantages in terms of lipoprotein (a) levels and insulin resistance compared to high-intensity statin monotherapy, suggesting potential metabolic benefits.