Metabolic and Safety Outcomes of Statin-Ezetimibe Versus High-Intensity Statin in Older Patients

High-intensity statins are recommended for secondary prevention in atherosclerotic cardiovascular disease (ASCVD), but older adults frequently experience tolerability issues and adverse metabolic effects. Moderate-intensity statin plus ezetimibe can achieve substantial low-density lipoprotein cholesterol lowering, yet randomized data comparing metabolic and safety outcomes versus high-intensity statins in older patients remain limited.

This subgroup analysis of the randomized SaveSAMS (Effects of High-Dose Statin Versus Low-Dose Statin Plus Ezetimibe on SAMS and on Reaching Target LDL-Cholesterol Levels Among Older Patients With ASCVD) trial included patients aged ≥70 years with established ASCVD assigned to high-intensity statin monotherapy (rosuvastatin 20 mg) or a moderate-intensity statin plus ezetimibe (rosuvastatin 5 mg/ezetimibe 10 mg). Among 318 patients (monotherapy, n=168; combination, n=150), 6-month changes in lipid parameters, metabolic biomarkers, and safety end points were compared.

Both strategies significantly improved lipid profiles. Combination therapy achieved greater non-high-density lipoprotein cholesterol reduction (Δ -76.0 versus -66.0 mg/dL; P=0.047) and attenuated statin-associated increases in lipoprotein(a) (Δ +0.1 versus +1.2 mg/dL; P=0.033). Statin-associated muscle symptoms occurred less frequently with combination therapy (0.7% versus 5.4%; P=0.021). New-onset diabetes did not differ significantly between groups (5.1% versus 14.5%; P=0.065), while changes in glycemic markers were similar. Low-density lipoprotein cholesterol target attainment (<70 and <55 mg/dL) was comparable between groups.

In older patients with ASCVD, a moderate-intensity statin plus ezetimibe provided low-density lipoprotein cholesterol lowering comparable with high-intensity statin monotherapy, with a more favorable metabolic and safety profile, including greater non-high-density lipoprotein cholesterol reduction, stable lipoprotein(a), and fewer muscle symptoms.

URL: https://www.clinicatrials.gov; Unique Identifier: NCT04826354.