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
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Japan
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Japan.
Eur J Prev Cardiol. 2016 Sep;23(14):1524-8. doi: 10.1177/2047487316655465. Epub 2016 Jun 13.
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.
IMPROVE-IT试验表明，他汀类药物/依折麦布联合治疗对接受过他汀类药物治疗的患者似乎具有显著的临床益处。我们推测，阿托伐他汀/依折麦布联合治疗对接受过他汀类药物预处理的患者具有显著的抗动脉粥样硬化作用。
在一项前瞻性、随机、对照、多中心的PRECISE-IVUS试验中，246例接受血管内超声引导下经皮冠状动脉介入治疗的患者被随机分为阿托伐他汀/依折麦布联合治疗组或单用阿托伐他汀组。两组均上调阿托伐他汀剂量，治疗目标是将低密度脂蛋白胆固醇降至70mg/dl以下。在基线和9至12个月随访时进行系列血管内超声容积测量，以量化202例患者的冠状动脉斑块反应。我们比较了所有受试者的血管内超声终点，并根据是否接受过他汀类药物预处理进行分层。
接受过他汀类药物预处理的患者基线时低密度脂蛋白胆固醇水平（100.7±23.1mg/dl对116.4±25.9mg/dl，p<0.001）和羊毛甾醇水平（55（38至87）μg/100mg总胆固醇对97（57至149）μg/100mg总胆固醇，p<0.001）显著更低，而菜油甾醇/羊毛甾醇比值（3.9（2.4至7.4）对2.6（1.5至4.1），p<0.001）显著升高。与未接受过他汀类药物预处理的患者相比（-1.3（-3.1至-0.1）%对-0.9（-2.3至0.9）%，p=0.12），在接受过他汀类药物预处理的患者中，阿托伐他汀/依折麦布联合治疗与单用阿托伐他汀相比，粥样硬化体积变化百分比的降低显著更强（-1.8（-3.6至-0.3）%对-0.1（-1.6至0.8）%，p=0.002）。
在接受他汀类药物治疗的患者中观察到的胆固醇吸收代偿性增加可能会减弱他汀类药物对冠状动脉斑块进展的抑制作用。低剂量他汀类药物/依折麦布联合治疗可能是他汀类药物低反应者的一个有前景的选择。
