Association Between Very Low Levels of High-Density Lipoprotein Cholesterol and Long-term Outcomes of Patients With Acute Coronary Syndrome Treated Without Revascularization: Insights From the TRILOGY ACS Trial.

Background Low levels of high-density lipoprotein cholesterol (HDL-C; <40 mg/dL) are associated with increased risk of cardiovascular events, but it is unclear whether lower thresholds (<30 mg/dL) are associated with increased hazard. Hypothesis Very low levels of HDL-C may provide prognostic information in acute coronary syndrome (ACS) patients treated medically without revascularization. Methods We examined data from 9064/9326 ACS patients enrolled in the TRILOGY ACS trial. Participants were randomized to clopidogrel or prasugrel plus aspirin. Study treatments continued for 6 to 30 months. Relationships between baseline HDL-C and the composite of cardiovascular death, myocardial infarction (MI), or stroke, and individual endpoints of death (cardiovascular and all-cause), MI, and stroke, adjusted for baseline characteristics through 30 months, were analyzed. The HDL-C was evaluated as a dichotomous variable—very low (<30 mg/dL) vs higher (≥30 mg/dL)—and continuously. Results Median baseline HDL-C was 42 mg/dL (interquartile range, 34–49 mg/dL) with little variation over time. Frequency of the composite endpoint was similar for very low vs higher baseline HDL-C, with no risk difference between groups (hazard ratio [HR]: 1.13, 95% confidence interval [CI]: 0.95-1.34). Similar findings were seen for MI and stroke. However, risks for cardiovascular (HR: 1.42, 95% CI: 1.13-1.78) and all-cause death (HR: 1.36, 95% CI: 1.11-1.67) were higher in patients with very low baseline HDL-C. Conclusions Medically managed ACS patients with very low baseline HDL-C levels have higher risk of long-term cardiovascular and all-cause death but similar risks for nonfatal ischemic outcomes vs patients with higher baseline HDL-C.