Meuwese Marijn C, de Groot Eric, Duivenvoorden Raphaël, Trip Mieke D, Ose Leiv, Maritz Frans J, Basart Dick C G, Kastelein John J P, Habib Rafik, Davidson Michael H, Zwinderman Aeilko H, Schwocho Lee R, Stein Evan A
Department of Vascular Medicine, Academic Medical Center, PO Box 22700, 1100 DE Amsterdam, The Netherlands.
JAMA. 2009 Mar 18;301(11):1131-9. doi: 10.1001/jama.301.11.1131.
Inhibition of acyl coenzyme A:cholesterol acyltransferase (ACAT), an intracellular enzyme involved in cholesterol accumulation, with pactimibe was developed to assist in the prevention of cardiovascular disease.
To evaluate the efficacy and safety of pactimibe in inhibition of atherosclerosis.
DESIGN, SETTING, AND PATIENTS: A prospective, randomized, stratified, double-blind, placebo-controlled study (Carotid Atherosclerosis Progression Trial Investigating Vascular ACAT Inhibition Treatment Effects [CAPTIVATE]) of 892 patients heterozygous for familial hypercholesterolemia conducted at 40 lipid clinics in the United States, Canada, Europe, South Africa, and Israel between February 1, 2004, and December 31, 2005. Study was terminated on October 26, 2005.
Participants received either 100 mg/d of pactimibe (n = 443) or matching placebo (n = 438), in addition to standard lipid-lowering therapy.
Carotid atherosclerosis, assessed by ultrasound carotid intima-media thickness (CIMT), at baseline, 12, 18, and 24 months. Maximum CIMT was the primary end point and mean CIMT the secondary end point.
Because pactimibe failed to show efficacy in the intravascular coronary ultrasound ACTIVATE study, the CAPTIVATE study was terminated prematurely after a follow-up of 15 months. After 6 months of treatment with pactimibe, low-density lipoprotein cholesterol increased by 7.3% (SD, 23%) compared with 1.4% (SD, 28%) in the placebo group (P = .001). The carotid ultrasonographic scans of the 716 patients with at least 2 scans and obtained at least 40 weeks apart were analyzed. Maximum CIMT measurements did not show a pactimibe treatment effect (difference, 0.004 mm; 95% confidence interval [CI], -0.023 to 0.015 mm; P = .64); however, the less variable mean CIMT measurement revealed an increase of 0.014 mm (95% CI, -0.027 to 0.000 mm; P = .04) in patients administered pactimibe vs placebo. Major cardiovascular events (cardiovascular death, myocardial infarction, and stroke) occurred more often in patients administered pactimibe vs placebo (10/443 [2.3%] vs 1/438 [0.2%]; P = .01).
In patients with familial hypercholesterolemia, pactimibe had no effect on atherosclerosis as assessed by changes in maximum CIMT compared with placebo but was associated with an increase in mean CIMT as well as increased incidence of major cardiovascular events.
clinicaltrials.gov Identifier: NCT00151788.
酰基辅酶A：胆固醇酰基转移酶（ACAT）是一种参与胆固醇蓄积的细胞内酶，开发了匹伐他汀来抑制该酶，以辅助预防心血管疾病。
评估匹伐他汀抑制动脉粥样硬化的疗效和安全性。
设计、地点和患者：一项前瞻性、随机、分层、双盲、安慰剂对照研究（颈动脉粥样硬化进展试验研究血管ACAT抑制治疗效果[CAPTIVATE]），于2004年2月1日至2005年12月31日在美国、加拿大、欧洲、南非和以色列的40家脂质诊所对892例家族性高胆固醇血症杂合子患者进行。研究于2005年10月26日终止。
除标准降脂治疗外，参与者接受100mg/d的匹伐他汀（n = 443）或匹配的安慰剂（n = 438）。
在基线、12、18和24个月时通过超声颈动脉内膜中层厚度（CIMT）评估颈动脉粥样硬化。最大CIMT是主要终点，平均CIMT是次要终点。
由于匹伐他汀在血管内冠状动脉超声ACTIVATE研究中未显示出疗效，CAPTIVATE研究在随访15个月后提前终止。匹伐他汀治疗6个月后，低密度脂蛋白胆固醇升高7.3%（标准差，23%），而安慰剂组升高1.4%（标准差，28%）（P = 0.001）。对716例至少进行了2次扫描且间隔至少40周的患者的颈动脉超声扫描进行了分析。最大CIMT测量未显示匹伐他汀治疗效果（差异，0.004mm；95%置信区间[CI]，-0.023至0.015mm；P = 0.64）；然而，变异性较小的平均CIMT测量显示，与安慰剂相比，接受匹伐他汀治疗的患者平均CIMT增加了0.014mm（95%CI，-0.027至0.000mm；P = 0.04）。主要心血管事件（心血管死亡、心肌梗死和中风）在接受匹伐他汀治疗的患者中比接受安慰剂治疗的患者更常见（10/443[2.3%]对1/438[0.2%]；P = 0.01）。
在家族性高胆固醇血症患者中，与安慰剂相比，根据最大CIMT变化评估，匹伐他汀对动脉粥样硬化无影响，但与平均CIMT增加以及主要心血管事件发生率增加相关。
clinicaltrials.gov标识符：NCT00151788。
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