Achieved LDL-C levels <55 mg/dL and cardiac events in patients and lesions harbouring lipid-rich plaque phenotypes

AIMS: The European Society of Cardiology guidelines recommend low-density lipoprotein cholesterol (LDL-C) < 55 mg/dL in very-high-risk patients. Given that plaque phenotype underscores its modulatory response to lipid-lowering therapies, patients and lesions harbouring lipid-laden plaques may benefit from LDL-C < 55 mg/dL to reduce their cardiovascular risks. METHODS AND RESULTS: The REASSURE-NIRS (REvelation of PAthophySiological PhenotypeS of VUlneRable Lipid-Rich PlaquE on Near-InfraRed Spectroscopy) multi-centre registry enrolled 853 coronary artery disease patients (non-culprit lesions = 1662) receiving NIRS/IVUS-guided PCI (NCT04864171). LDL-C level at 3 months after PCI was used as on-treatment LDL-C. Study subjects were stratified according to maxLCBI4mm at non-culprit lesions < vs. ≥324.7. In each group, major adverse cardiac events (MACE) (=cardiac-cause death + non-fatal myocardial infarction (MI) + ischaemia-driven non-culprit lesion revascularization) was compared in those with on-treatment LDL-C < vs. ≥55 mg/dL. 31.6% of study subjects achieved on-treatment LDL-C < 55 mg/dL. During the observational period (median = 1109 days), MACE rate did not differ in patients with maxLCBI4mm < 324.7 exhibiting on-treatment LDL-C levels < and ≥55 mg/dL [adjusted hazard ratio (HR) = 1.42, 95% confidence interval (CI) = 0.80-2.54, P = 0.227]. By contrast, in patients with non-culprit lesion maxLCBI4mm ≥ 324.7, a significantly reduced MACE rate was observed in those with on-treatment LDL-C < 55 mg/dL (adjusted HR = 0.23, 95% CI: 0.09-0.57, P = 0.010). These relationships were similarly observed in a lesion-based analysis (non-culprit lesion maxLCBI4mm < 324.7: adjusted HR = 1.30, 95% CI = 0.42-4.00, P = 0.640, non-culprit lesion maxLCBI4mm ≥ 324.7: adjusted HR = 0.27, 95% CI:0.08-0.97, P = 0.045). Notably, in patients with multiple non-culprit lesions with maxLCBI4mm ≥ 324.7, on-treatment LDL-C < 55 mg/dL was associated with a lower frequency of MACE (adjusted HR = 0.22, 95% CI = 0.09-0.53, P < 0.001), whereas this relationship was not observed in those with single non-culprit lesion with maxLCBI4mm ≥ 324.7 (adjusted HR = 0.03, 95% CI = 0.00-5.55, P = 0.196). CONCLUSION: NIRS-derived lipid-rich plaque may be a potential imaging measure reflecting patients and lesions that may benefit from achieving LDL-C levels < 55 mg/dL.