Baseline, delta, and achieved low‐density lipoprotein cholesterol levels and cardiovascular risk in patients on statin therapy: A post‐hoc resampling mediation analysis of treating new targets [TNT] trial. (17th July 2020) - Hyun, Myung Han
Abstract: Clinical guidelines for monitoring low‐density lipoprotein cholesterol (LDL‐C) after statin therapy do not clearly define the clinical roles of baseline LDL‐C, ΔLDL‐C, and achieved LDL‐C according to statin intensity. We performed post‐hoc analysis of the Treating to New Target (TNT) study to evaluate individual LDL‐C parameters after statin therapy. Primary outcome was the risk for total major adverse cardiovascular events (MACE). We use resampling multilevel mediation analysis to analyze complex relationships among LDL‐C parameters based on similar statin intensities. Tertiles for resample A (matched baseline LDL‐C; distinct achieved LDL), resample B (matched ΔLDL‐C; distinct baseline LDL‐C), and resample C (matched achieved LDL‐C; distinct ΔLDL‐C) were analyzed using Cox proportional hazard ratios. In original data analysis, the incidence of MACE was reduced in those with lower achieved LDL‐C in total, low, and high intensity statin users (hazard ratios [HRs] = 0.990, 0.992, 0.992; respectively; all P ‐values < .001). In mediation analysis, resample A showed consistently high incidence for MACE in the middle tertile (HR = 1.237; 95% confidential interval [CI] = 1.008‐1.517; P ‐value = .041) and highest tertile (HR = 1.275; 95% CI = 1.021‐1.592; P ‐value = .032) compared to the lowest tertile. However, resamples B and C did not show consistent differences. Similarly, no consistent statistical difference in MACE according to statin intensity. Lower achieved LDL‐C decreased MACE in participants with a similar baseline LDL‐C after statin therapy. However, the change in absolute values of ΔLDL‐C and achieved LDL‐C should be interpreted in an individualized manner due to their complex collinearity, and statin intensity should also be taken into consideration.