Abstract 14994: How Low Should You Go in Secondary Prevention Treatment of LDL Cholesterol: Observational Insights from the Intermountain Heart Collaborative Study

Abstract

Introduction: Epidemiologic studies have identified high LDL cholesterol levels as an independent risk factor for cardiovascular (CV) disease, and randomized trials with statin therapy have demonstrated added clinical benefit when LDL levels are reduced to at least 70 mg/dL. However, whether targeting significantly lower secondary prevention LDL levels is beneficial, or perhaps actually may be unsafe, is not known. Methods: Patients undergoing coronary angiography who were documented to have significant (≥50% stenosis) coronary artery disease (CAD), discharged on statin therapy with an LDL level <100 mg/dL and had ≤3y clinical follow-up were studied. Patients were stratified, according to on-statin LDL levels, into ultra low (<40 mg/dL [n=221]), very low (40-69 mg/dL [n=1,684]) and low (70-99 mg/dL [n=3,317]) categories and followed for the long-term endpoints of all-cause death, cardiac death, non-cardiac death, MI, stroke, coronary revascularization (CR) and MACE (death, MI, stroke, CR). Hazard ratios (HRs) comparing the three LDL groups were calculated by Cox regression, adjusting for 17 baseline variables. Results: A total of 5,222 patients (age = 66±12 yrs, men = 72%, hypertension = 69%, diabetes = 30%, smokers = 29%, ACS presentation = 69%) were studied. Follow-up for the ultra low, very low and low LDL categories was 6.1±4.3, 6.4±3.9 and 7.3±4.1 yrs respectively. Event rates and adjusted HRs are shown in the Table. Conclusions: In a large secondary prevention population with significant CAD on statin therapy, treating LDL cholesterol levels to <70 mg/dL compared to 70-99 mg/dL was not associated with superior long-term CV outcomes. From a non-CV standpoint, LDL levels down to 40 mg/dL appeared to be safe, but ultra low LDL levels (<40 mg/dL) were associated with a significantly increased risk of non-CV death. Based on this information, very aggressive secondary prevention treatment of LDL cholesterol to levels below 40 mg/dL may require further study.