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



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.



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).



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.
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Japan tsujita@kumamoto-u.ac.jp.
Kenichi
K
Tsujita
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Japan.
Kenshi
K
Yamanaga
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Japan.
Naohiro
N
Komura
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Japan.
Kenji
K
Sakamoto
Jinnouchi Hospital, Kumamoto, Japan.
Seigo
S
Sugiyama
Division of Cardiology, Kumamoto Central Hospital, Japan.
Hitoshi
H
Sumida
Department of Cardiovascular Medicine, Fukuoka Tokushukai Medical Center, Kasuga, Japan.
Hideki
H
Shimomura
Division of Cardiology, Social Insurance Omuta Tenryo Hospital, Omuta, Japan.
Takuro
T
Yamashita
Division of Cardiology, Health Insurance Hitoyoshi General Hospital, Japan.
Hideki
H
Oka
Division of Cardiology, Saiseikai Kumamoto Hospital Cardiovascular Center, Kumamoto, Japan.
Koichi
K
Nakao
Interventional Cardiology Unit, New Tokyo Hospital, Matsudo, Japan.
Sunao
S
Nakamura
Division of Coronary Artery Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Masaharu
M
Ishihara
Department of Community Medicine, Kumamoto University, Japan.
Kunihiko
K
Matsui
Division of Cardiology, Amakusa Medical Center, Japan.
Naritsugu
N
Sakaino
Division of Cardiology, Shin-Beppu Hospital, Beppu, Japan.
Natsuki
N
Nakamura
Division of Cardiology, Miyazaki Prefectural Nobeoka Hospital, Japan.
Nobuyasu
N
Yamamoto
Division of Cardiology, Health Insurance Kumamoto General Hospital, Yatsushiro, Japan.
Shunichi
S
Koide
Division of Cardiology, Japan Labor Health and Welfare Organization Kumamoto Rosai Hospital, Yatsushiro, Japan.
Toshiyuki
T
Matsumura
National Hospital Organization Kumamoto Medical Center, Japan.
Kazuteru
K
Fujimoto
Japanese Red Cross Kumamoto Hospital, Japan.
Ryusuke
R
Tsunoda
Division of Cardiology, Kumamoto City Hospital, Japan.
Yasuhiro
Y
Morikami
Division of Cardiology, Social Insurance Omuta Tenryo Hospital, Omuta, Japan.
Koushi
K
Matsuyama
Division of Cardiology, Kumamoto Central Hospital, Japan.
Shuichi
S
Oshima
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Japan.
Koichi
K
Kaikita
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Japan.
Seiji
S
Hokimoto
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Japan Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
Hisao
H
Ogawa
D000924:Anticholesteremic Agents / Q000008:administration & dosage; D000069059:Atorvastatin / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D000069438:Ezetimibe / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D011446:Prospective Studies; D016037:Single-Blind Method; D016896:Treatment Outcome; D018084:Ultrasonography, Interventional
D000924:Anticholesteremic Agents; D015415:Biomarkers; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C001521:lathosterol; D002784:Cholesterol; D000069059:Atorvastatin; D000069438:Ezetimibe
Ezetimibe; HMG-CoA reductase inhibitors; intravascular ultrasound; plaque