Synergistic effect of ezetimibe addition on coronary atheroma regression in patients with prior statin therapy: Subanalysis of PRECISE-IVUS trial. (September 2016)

• Record Type: Journal Article
• Authors: Tsujita, Kenichi; Yamanaga, Kenshi; Komura, Naohiro; Sakamoto, Kenji; Sugiyama, Seigo; Sumida, Hitoshi; Shimomura, Hideki; Yamashita, Takuro; Oka, Hideki; Nakao, Koichi; Nakamura, Sunao; Ishihara, Masaharu; Matsui, Kunihiko; Sakaino, Naritsugu; Nakamura, Natsuki; Yamamoto, Nobuyasu; Koide, Shunichi; Matsumura, Toshiyuki; Fujimoto, Kazuteru; Tsunoda, Ryusuke; Morikami, Yasuhiro; Matsuyama, Koushi; Oshima, Shuichi; Kaikita, Koichi; Hokimoto, Seiji; Ogawa, Hisao
• Is Part Of: European journal of preventive cardiology. Volume 23:Number 14(2016)
• Page Start: 1524
• Page End: 1528
• Publication Date: 2016-09
• Subjects: Ezetimibe -- HMG-CoA reductase inhibitors -- plaque -- intravascular ultrasound; Cardiovascular system -- Diseases -- Prevention -- Periodicals; Cardiac patients -- Rehabilitation -- Periodicals; 616.12
• DOI: 10.1177/2047487316655465
• Languages: English
• ISSNs: 2047-4873

Abstract

Background: The IMPROVE-IT trial showed that the clinical benefit of statin/ezetimibe combination appeared to be pronounced in patients with prior statin therapy. We hypothesized that the antiatherosclerotic effect of atorvastatin/ezetimibe combination was pronounced in patients with statin pretreatment. Methods: In the prospective, randomized, controlled, multicenter PRECISE-IVUS trial, 246 patients undergoing intravascular ultrasound-guided percutaneous coronary intervention were randomized to atorvastatin/ezetimibe combination or atorvastatin alone. The dosage of atorvastatin was uptitrated with a treatment goal of lowering low-density lipoprotein cholesterol to below 70 mg/dl in both groups. Serial volumetric intravascular ultrasound was performed at baseline and 9–12 month follow-up to quantify the coronary plaque response in 202 patients. We compared the intravascular ultrasound endpoints in all subjects, stratified by the presence or absence of statin pretreatment. Results: The baseline low-density lipoprotein cholesterol level (100.7 ± 23.1 mg/dl vs. 116.4 ± 25.9 mg/dl, p < 0.001) and lathosterol (55 (38 to 87)) µg/100 mg total cholesterol vs. 97 (57 to 149) µg/100 mg total cholesterol, p < 0.001) was significantly lower, and campesterol/lathosterol ratio (3.9 (2.4 to 7.4) vs. 2.6 (1.5 to 4.1), p < 0.001) was significantly increased in patients with statin pretreatment. Contrary to the patients without statin pretreatment (−1.3 (−3.1 to −0.1)% vs. −0.9 (−2.3 to 0.9)%, p = 0.12), the atorvastatin/ezetimibe combination showed a significantly stronger reduction in delta percent atheroma volume, compared with atorvastatin alone, in patients with statin pretreatment (−1.8 (−3.6 to −0.3)% vs. −0.1 (−1.6 to 0.8)%, p = 0.002). Conclusion: Compensatory increase in cholesterol absorption observed in statin-treated patients might attenuate the inhibitory effects of statins on coronary plaque progression. A low-dose statin/ezetimibe combination might be a promising option in statin-hyporesponder.