Abstract 14501: Relation of Lipoprotein Levels to Cardiovascular Events in the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes (AIM-HIGH) Trial

Abstract

BACKGROUND: During a mean 3-year follow-up in 3,414 patients with established cardiovascular (CV) disease and low baseline HDL-C, combined therapy with statin + extended-release niacin (ERN) did not reduce CV events vs intensive statin therapy alone. Whether these findings may vary by lipoprotein levels remains unknown. METHODS: Subjects taking simvastatin (S) + ezetimibe (E) were randomized to ERN 1500-2000 mg or placebo at bedtime. Doses of S/E were adjusted to maintain LDL-C from 40 to 80 mg/dL. ERN treatment effects were examined within baseline lipoprotein tertiles. Cox proportional hazards models were used to estimate the hazard ratio (HR) for relationships between continuous lipoprotein variables and the primary, composite endpoint of CV death, MI, acute coronary syndrome, ischemic stroke, or symptom-driven coronary/carotid revascularization.

RESULTS: No significant CV benefit or harm was associated with ERN use in any tertile of LDL-C, triglyceride (TG), HDL-C, non-HDL-C, TC/HDL-C ratio or TG/HDL-C ratio. In the subset of 524 patients in both the highest TG (>198 mg/dl) and lowest HDL-C (<33 mg/dl) tertiles, ERN use showed a trend toward benefit (HR=0.74, p=0.073). In continuous models adjusted for covariates, baseline TC/HDL-C and in-trial LDL-C, non-HDL-C, and TC/HDL-C showed expected relationships with CV events in placebo group (Table, P=0.006 to P=0.06), but these trends were absent in ERN-treated subjects. Unadjusted models gave similar results.

CONCLUSION: In AIM-HIGH, lipoprotein levels did not predict differential benefit or harm with ERN. In ERN-treated subjects, expected effects of lipoprotein risk factors on CV events were absent. Potential mechanisms whereby ERN may attenuate expected relationships of lipoproteins and atherosclerotic risk warrant further study.