Effects of statin therapy on coronary artery plaque volume and high-risk plaque morphology in HIV-infected patients with subclinical atherosclerosis: a randomised, double-blind, placebo-controlled trial.
Effects of statin therapy on coronary artery plaque volume and high-risk plaque morphology in HIV-infected patients with subclinical atherosclerosis: a randomised, double-blind, placebo-controlled trial.
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DOI：
10.1016/s2352-3018(14)00032-0
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发表时间：
2015-02
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影响因子：
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通讯作者：
Grinspoon SK
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作者：
Lo J;Lu MT;Ihenachor EJ;Wei J;Looby SE;Fitch KV;Oh J;Zimmerman CO;Hwang J;Abbara S;Plutzky J;Robbins G;Tawakol A;Hoffmann U;Grinspoon SK
目前还没有研究评估他汀类药物治疗在HIV感染患者中减少动脉炎症和实现冠状动脉粥样硬化消退的能力，HIV感染患者是心肌梗死风险升高的人群。在一项随机、双盲、安慰剂对照试验中，40名患有亚临床冠状动脉粥样硬化、氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）显示主动脉炎症证据且低密度脂蛋白（LDL）胆固醇<3·37mmol/L（130mg/dL）的HIV感染参与者被随机分配至阿托伐他汀（n = 19）或安慰剂（n = 21）治疗一年。由MGH临床研究药房使用排列区组算法进行随机化，按性别分层，固定区组大小为4，1：1分配至阿托伐他汀或相同匹配的安慰剂。研究代码仅提供给MGH Research Pharmacy，不提供给研究者或受试者。预先规定的主要终点是动脉炎症，通过主动脉的FDG-PET进行评估。其他预先规定的终点包括冠状动脉计算机断层扫描血管造影评估的冠状动脉粥样硬化斑块。我们定量评估了非钙化和钙化斑块以及高危斑块的特征。采用意向治疗原则，使用所有可用数据进行分析，不对缺失数据进行插补。40例受试者中有37例（92.5%）完成了研究，两组的停药率相同。两组之间的基线参数相似。12个月后，阿托伐他汀组和安慰剂组主动脉病变最严重节段的FDG-PET摄取变化无差异，但仅在一部分患者中评估了比较相同区域纵向变化的技术充分结果（阿托伐他汀Δ − 0·03 [95% CI：− 0·17，0·12] vs安慰剂Δ − 0·06 [− 0·25，0·13]，p = 0·77，n = 21）。可以在完成研究的所有受试者中评估斑块的变化。与安慰剂相比，阿托伐他汀减少了非钙化冠状动脉斑块体积（− 19·4%（IQR：− 39·2%，9·3%）vs.+20统计学4%（− 7·1%，94·4%），p = 0·009，n = 37）。此外，与安慰剂相比，阿托伐他汀显著减少了高危斑块的数量（低衰减斑块数量变化-0.2 [95%CI：− 0·6，0·2] vs. 0·4 [0·0，0·7]，p = 0·03，n = 37，阳性重塑斑块数量变化− 0·2 [95% CI − 0·4，0·1] vs. 0·4 [− 0·1，0·8]，p = 0·04，n = 37）。直接LDL-胆固醇（− 1·00 [95% CI − 1·38，0·61] vs. 0·30 [0·04，0·55] mmol/L，p <0·0001）和脂蛋白相关磷脂酶A2与安慰剂相比，阿托伐他汀组（− 52·2 [95% CI − 70·4，− 34·0] vs. − 13·3 [− 32·8，6·2] ng/mL，p = 0·005，n = 37）显著降低。他汀类药物治疗耐受性良好，临床不良事件发生率低。与安慰剂相比，他汀类药物治疗可减少HIV感染伴亚临床冠状动脉粥样硬化患者的非钙化斑块体积和高危斑块特征。通过FDG-PET未观察到他汀类药物治疗对主动脉炎症的显著影响。进一步的研究应该评估在高危人群中，高危冠状动脉疾病的减少是否转化为心血管事件的有效预防。
No studies have yet assessed the ability of statin treatment to reduce arterial inflammation and achieve regression of coronary atherosclerosis in HIV-infected patients, a population with elevated risk of myocardial infarction. In a randomized, double-blind, placebo-controlled trial, 40 HIV-infected participants with subclinical coronary atherosclerosis, evidence of arterial inflammation in the aorta by fluorodeoxyglucose positron emission tomography (FDG-PET) and low density lipoprotein(LDL)-cholesterol <3·37mmol/L(130mg/dL) were randomized to one year of treatment with atorvastatin (n=19) or placebo (n=21). Randomization was carried out by the MGH Clinical Research Pharmacy using a permuted-block algorithm, stratified by gender with a fixed block size of four, with 1:1 allocation to atorvastatin or identical matching placebo. Study codes were available only to the MGH Research Pharmacy and not to study investigators or participants. The prespecified primary endpoint was arterial inflammation, as assessed by FDG-PET of the aorta. Additional prespecified endpoints included coronary atherosclerotic plaque as assessed by coronary computed tomography angiography. We quantitatively assessed non-calcified and calcified plaque and high risk plaque features. Analysis was performed using intention-to-treat principle, using all available data, without imputation for missing data. Thirty seven out of forty (92·5%) subjects completed the study, with equivalent discontinuation rates in both groups. Baseline parameters were similar between groups. After 12 months, change in FDG-PET uptake of the most diseased segment of the aorta was not different between atorvastatin and placebo, but technically adequate results comparing longitudinal changes in identical regions could only be assessed in a subset of patients (atorvastatin Δ −0·03 [95% CI: −0·17, 0·12] vs. placebo Δ −0·06 [−0·25, 0·13], p=0·77, n=21). Change in plaque could be assessed in all subjects completing the study. Atorvastatin reduced noncalcified coronary plaque volume compared to placebo (−19·4%(IQR: −39·2%, 9·3%) vs. +20·4%(−7·1%, 94·4%), p=0·009, n=37). In addition, the number of high risk plaques was significantly reduced by atorvastatin compared to placebo (change in number of low attenuation plaques −0·2[95% CI: −0·6, 0·2] vs. 0·4[0·0, 0·7], p=0·03, n=37 and change in number of positively remodeled plaques −0·2[95% CI −0·4, 0·1] vs. 0·4[−0·1, 0·8], p=0·04, n=37). Direct LDL-cholesterol (−1·00[95% CI −1·38, 0·61] vs. 0·30[0·04, 0·55] mmol/L, p<0·0001) and lipoprotein-associated phospholipase A2 (−52·2[95% CI −70·4, −34·0] vs. −13·3[−32·8, 6·2] ng/mL, p=0·005, n=37) significantly decreased with atorvastatin compared to placebo. Statin therapy was well-tolerated, with low incidence of clinical adverse events. Compared to placebo, statin therapy reduces noncalcified plaque volume and high risk plaque features in HIV-infected patients with subclinical coronary atherosclerosis. Significant effects of statin therapy on arterial inflammation of the aorta by FDG-PET were not seen. Further studies should assess whether reduction in high risk coronary artery disease translates into effective prevention of cardiovascular events in this at risk population.