South Australian Health and Medical Research Institute, Adelaide, Australia.
JAMA. 2013 Sep 18;310(11):1135-44. doi: 10.1001/jama.2013.277169.
Blood pressure reduction and renin-angiotensin-aldosterone system inhibition are targets for treatment of atherosclerosis. The effect of renin inhibition on coronary disease progression has not been investigated.
To determine the effects of renin inhibition with aliskiren on progression of coronary atherosclerosis.
DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial (Aliskiren Quantitative Atherosclerosis Regression Intravascular Ultrasound Study) comparing aliskiren with placebo in 613 participants with coronary artery disease, systolic blood pressure between 125 and 139 mm Hg (prehypertension range), and 2 additional cardiovascular risk factors conducted at 103 academic and community hospitals in Europe, Australia, and North and South America (enrollment from March 2009 to February 2011; end of follow-up: January 31, 2013).
Participants underwent coronary intravascular ultrasound (IVUS) imaging and were randomized to receive 300 mg of aliskiren (n = 305) or placebo (n = 308) taken orally daily for 104 weeks. Disease progression was measured by repeat IVUS examination after at least 72 weeks of treatment.
The primary efficacy parameter was the change in percent atheroma volume (PAV) from baseline to study completion. Secondary efficacy parameters included the change in normalized total atheroma volume (TAV) and the percentage of participants with atheroma regression. Safety and tolerability were also assessed.
Evaluable imaging data were available at baseline and follow-up for 458 participants (74.7%). The primary IVUS efficacy parameter, PAV, did not differ between participants treated with aliskiren (-0.33%; 95% CI, -0.68% to 0.02%) and placebo (0.11%; 95% CI, -0.24% to 0.45%) (between-group difference, -0.43% [95% CI, -0.92% to 0.05%]; P = .08). The secondary IVUS efficacy parameter, TAV, did not differ between participants treated with aliskiren (-4.1 mm3; 95% CI, -6.27 to -1.94 mm3) and placebo (-2.1 mm3; 95% CI, -4.21 to 0.07 mm3) (between-group difference, -2.04 mm3 [95% CI, -5.03 to 0.95 mm3]; P = .18). There were no significant differences in the proportion of participants who demonstrated regression of PAV (56.9% vs 48.9%; P = .08) and TAV (64.4% vs 57.5%; P = .13) in the aliskiren and placebo groups, respectively.
Among participants with prehypertension and coronary artery disease, the use of aliskiren compared with placebo did not result in improvement or slowing of progression of coronary atherosclerosis. These findings do not support the use of aliskiren for regression or prevention of progression of coronary atherosclerosis.
clinicaltrials.gov Identifier: NCT00853827.
血压降低和肾素-血管紧张素-醛固酮系统抑制是治疗动脉粥样硬化的目标。肾素抑制对冠状动脉疾病进展的影响尚未得到研究。
确定肾素抑制用阿利克仑对冠状动脉粥样硬化进展的影响。
设计、地点和参与者：一项双盲、随机、多中心试验（阿利克仑定量动脉粥样硬化消退血管内超声研究），在欧洲、澳大利亚和北美和南美 103 家学术和社区医院比较了阿利克仑与安慰剂在 613 例患有冠状动脉疾病、收缩压在 125 至 139 毫米汞柱（高血压前期范围）和 2 个额外心血管风险因素的参与者中的作用。招募于 2009 年 3 月至 2011 年 2 月进行；随访结束：2013 年 1 月 31 日。
参与者接受冠状动脉血管内超声（IVUS）成像，并随机接受 300 毫克阿利克仑（n=305）或安慰剂（n=308）每天口服，持续 104 周。在至少 72 周的治疗后，通过重复 IVUS 检查来测量疾病进展。
主要疗效参数是从基线到研究完成时的粥样斑块体积百分比（PAV）的变化。次要疗效参数包括标准化总粥样斑块体积（TAV）的变化和粥样斑块消退的参与者比例。还评估了安全性和耐受性。
458 名参与者（74.7%）有可评估的成像数据。接受阿利克仑治疗的参与者（-0.33%；95%置信区间，-0.68%至 0.02%）和安慰剂（0.11%；95%置信区间，-0.24%至 0.45%）的主要 IVUS 疗效参数 PAV 没有差异（组间差异，-0.43%[95%置信区间，-0.92%至 0.05%]；P=0.08）。接受阿利克仑治疗的参与者（-4.1 毫米 3；95%置信区间，-6.27 至-1.94 毫米 3）和安慰剂（-2.1 毫米 3；95%置信区间，-4.21 至 0.07 毫米 3）的次要 IVUS 疗效参数 TAV 没有差异（组间差异，-2.04 毫米 3[95%置信区间，-5.03 至 0.95 毫米 3]；P=0.18）。阿利克仑组和安慰剂组分别有 56.9%和 48.9%的参与者 PAV（P=0.08）和 TAV（P=0.13）出现消退，差异无统计学意义。
在患有高血压前期和冠状动脉疾病的参与者中，与安慰剂相比，使用阿利克仑并没有改善或减缓冠状动脉粥样硬化的进展。这些发现不支持使用阿利克仑来促进冠状动脉粥样硬化的消退或预防进展。
clinicaltrials.gov 标识符：NCT00853827。
