Abstract 4142452: LDL-C variability was affected by lipid-lowering strategies and associated with adverse cardiovascular outcomes

Background: Prior studies have shown an independent association between visit-to-visit variability in low-density lipoprotein cholesterol (LDL-C) and adverse cardiovascular (CV) events and that this variability can be reduced by high-intensity statins (HIS). However, it is not known whether LDL-C variability can be reduced by moderate-intensity statin (MIS) plus ezetimibe combination or by a treat-to-target strategy (TTS). Hypothesis: We aimed to evaluate whether visit-to-visit variability in LDL-C is affected by lipid-lowering strategies and its association with CV outcomes in patients treated with HIS or MIS plus ezetimibe or statins with a target LDL-C levels of 50 to 70 mg/dL (TTS). Methods: Data from the RACING and LODESTAR trial in patients with atherosclerotic disease, LDL-C variability was evaluated from 3 months after randomization. In the RACING trial, MIS plus ezetimibe combination therapy was compared with HIS monotherapy. In the LODESTAR trial, TTS with a target LDL-C level of 50 to 70 mg/dL by titration of the statin intensity was compared with HIS strategy. LDL-C variability was compared according to these lipid-lowering strategies. The primary endpoint was a composite of death, myocardial infarction, stroke, or coronary revascularization. Results: Among the 6800 patients included, when compared with patients randomized to HIS, LDL-C variability was similar in the group randomized to MIS plus ezetimibe combination (SD 8.92±7.15 vs 9.17±7.34, P=0.325) but higher in those randomized to TTS (SD 8.9±7.2 vs 10.6±7.7, P=0.001). There was a linear association between LDL-C variability and primary endpoint (Figure 1). The variability in LDL-C (by SD) was a predictor of primary endpoint (HR 1.024; 95% CI 1.014 to 1.035; P<0.001) even after adjustment for lipid-lowering strategy and mean LDL-C. Conclusions: Compared with HIS therapy, visit-to-visit variability in LDL-C was not increased in the MIS plus ezetimibe combination therapy, but was increased in the TTS. Even in those treated with MIS plus ezetimibe or HIS or statins with a target LDL-C levels of 50 to 70 mg/dL, increased LDL-C variability was significantly associated with higher risk of adverse CV outcome.