The effects of STAtin-FENOfibrate combination therapy vs. statin monotherapy on necrotic core and plaque characteristics in non-diabetic patients with combined dyslipidemia and intermediate CAOD

Background Residual cardiovascular risk remains in statin-treated patients with combined dyslipidemia. Fenofibrate may offer additive benefits by targeting triglyceride-rich lipoproteins and associated metabolic abnormalities. Objectives To evaluate the effects of statin plus fenofibrate combination therapy versus statin monotherapy on coronary plaque burden and composition, assessed by virtual histology intravascular ultrasound (VH-IVUS), in non-diabetic patients with combined dyslipidemia. Methods In this prospective, randomized, multicenter, open-label trial, non-diabetic patients with combined dyslipidemia and intermediate coronary artery stenosis were assigned to receive rosuvastatin 10 mg/day with or without fenofibrate 160 mg/day. VH-IVUS imaging and laboratory assessments were performed at baseline and after 12 months. The primary endpoints were changes in absolute and percent necrotic core (NC) volume. Secondary analyses included changes in plaque phenotype and associations with lipid and metabolic parameters. Results Seventy-nine patients (mean age 57.6 ± 9.0 years; 96.2% male) with 89 lesions were analyzed (combination group: 36 patients, 38 lesions; statin group: 43 patients, 51 lesions). Both statin monotherapy and combination therapy with statin and fenofibrate significantly reduced plaque volume over a 12-month period (p = 0.04 and p = 0.02, respectively). In the combination group, both absolute NC volume (23.3 ± 25.6 mm³ to 17.8 ± 14.9 mm³, p = 0.03) and percent NC volume (15.4 ± 7.5% to 13.5 ± 6.6%, p = 0.04) were significantly reduced. No significant changes were observed in the statin group. The combination group showed a trend toward greater percent NC reduction compared to statin alone (p = 0.11). Changes in VH phenotype demonstrated significant plaque stabilization in the combination group (stabilization: 5.9%, unchanged: 94.1%, destabilization: 0%) compared to the statin-monotherapy group (stabilization: 0%, unchanged: 91.9%, destabilization: 8.1%; p = 0.04). Reductions in NC and plaque volume in combination group were significantly associated with improvements in non–HDL cholesterol (LDL cholesterol plus remnant cholesterol, r=0.30, p=0.03), insulin resistance (HOMA-IR, r=0.38, p=0.02) and inflammation (Phospholipase A2, r=0.45, p=0.003). Conclusion In non-diabetic patients with combined dyslipidemia, combination therapy with statin and fenofibrate significantly reduced necrotic core volume and enhanced plaque stabilization, likely through favorable effects on Non-HDL cholesterol, insulin resistance, and inflammation.