Effects of Combination Therapy with Cilostazol and Probucol versus Monotherapy with Cilostazol on Coronary Plaque, Lipid and Biomarkers: SECURE Study, a Double-Blind Randomized Controlled Clinical Trial

摘要

Aim : The study aim is to investigate synergistic effects of cilostazol and probucol combination therapy on coronary plaque volume and composition. Methods : A total of 119 patients undergoing coronary stenting were treated with probucol and cilostazol combination therapy (group Ⅰ) or with cilostazol monotherapy (group Ⅱ) in a double-blind, randomized multicenter trial, and evaluated by virtual histology intravascular ultrasound (VH-IVUS) at baseline and 9-month follow-up for changes in coronary plaque volume and composition at an index intermediate lesion with luminal narrowing ≥30% and ＜70% and for neointimal hyperplasia at the stented segment. In all patients simvastatin 20 mg was started with enrollment. Results : Qualifying VH-IVUS data from 91 patients were included in the final analysis. There were no significant differences between group Ⅰ and Ⅱ with respect to the primary endpoint, nominal change in normalized total atheroma volume (TAV) of the index intermediate coronary lesion (Δ?12.6±17.7 vs. ?14.2±20.2 mm3, p =0.691), or plaque composition. Plaque regression was observed in more than 70% of patients in both groups. Diabetes was the only significant independent determinant of changes in TAV ( β =0.22, p =0.037). There were greater decreases in total cholesterol (Δ?51.8±33.0 vs. ?25.4±39.1 mg/dL, p ＜0.001) and LDL (Δ?33.5±30.5 vs. ?20.3±30.8 mg/dL, p =0.044) levels in group Ⅰ than in group Ⅱ. However, HDL cholesterol (Δ?11.2±8.5 vs. 2.7±7.7 mg/dL, p ＜0.001) and apoA1 (Δ?18.2±21.4 vs. 10.0±16.5 mg/dL, p ＜0.001) levels were also significantly decreased in group Ⅰ compared with group Ⅱ. Conclusions : There were no significant differences in changes in plaque volume or composition between the cilostazol and probucol combination therapy and cilostazol monotherapy group despite different impacts of the treatments on lipid biomarkers.