Puri Rishi, Nissen Steven E, Menon Venu, Shao Mingyuan, Hsu Amy, Bakris George L, Kastelein John J P, Williams Bryan, Armbrecht Juergen, Brunel Patrick, Kataoka Yu, Nicholls Stephen J
Cleveland Clinic Coordinating Center for Clinical Research (C5R), Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA; Department of Medicine, University of Adelaide, Adelaide, Australia.
Cleveland Clinic Coordinating Center for Clinical Research (C5R), Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA.
Atherosclerosis. 2015 Dec;243(2):553-9. doi: 10.1016/j.atherosclerosis.2015.10.019. Epub 2015 Oct 20.
Aliskiren previously was found to have potentially harmful effects in diabetic individuals prescribed concomitant angiotensin converting enzyme inhibitors (ACEI) or angiotenisn receptor antagonists (ARB). We explored potential effects of aliskiren on coronary atheroma progression and major adverse cardiovascular events (MACE: death/non-fatal MI/non-fatal stroke/hospitalization for heart failure/hospitalization for ACS/arterial revascularization) in patients with and without diabetes mellitus (DM).
AQUARIUS employed serial intravascular ultrasound measures of coronary atheroma volume in coronary artery disease patients randomized to receive daily aliskiren 300 mg or placebo for 104 weeks. This post hoc analysis compared changes in plaque volume [percent atheroma volume (PAV) and total atheroma volume (TAV)] and MACE in patients with (n = 115) and without (n = 343) DM stratified by treatment allocation.
In multivariable propensity-weighted analyses, which included controlling for baseline and concomitant ACEI/ARB therapy and duration of aliskiren therapy, aliskiren-treated non-DM patients demonstrated the greatest PAV and TAV regression, whereas aliskiren-treated DM patients demonstrated the greatest TAV progression and greater PAV. Aliskiren-treated non-DM patients appeared at significantly lower risk of MACE compared with their aliskiren-treated DM counterparts [HR 95% CI 0.28 (0.10, 0.80)]. Statistical interactions were noted between DM status and treatment allocation for both changes in PAV (p < 0.001), TAV (p = 0.010) and MACE (p = 0.057).
Aliskiren appears to be relatively anti-atherosclerotic in non-diabetic patients. Due to the limited number MACE and low numbers of diabetic patients in AQUARIUS, the pro-atherosclerotic effects of aliskiren in this population are inconclusive, and these results should be thus considered hypothesis generating. Further outcome studies are required in non-diabetic patients to confirm the possible favorable effects of aliskiren.
先前发现，在同时服用血管紧张素转换酶抑制剂（ACEI）或血管紧张素受体拮抗剂（ARB）的糖尿病患者中，阿利吉仑可能具有有害作用。我们探讨了阿利吉仑对伴有或不伴有糖尿病（DM）的患者冠状动脉粥样硬化进展和主要不良心血管事件（MACE：死亡/非致死性心肌梗死/非致死性卒中/因心力衰竭住院/因急性冠状动脉综合征住院/动脉血运重建）的潜在影响。
AQUARIUS研究对冠状动脉疾病患者采用连续血管内超声测量冠状动脉粥样硬化体积，这些患者被随机分配接受每日300毫克阿利吉仑或安慰剂治疗104周。这项事后分析比较了按治疗分配分层的糖尿病患者（n = 115）和非糖尿病患者（n = 343）的斑块体积变化[粥样硬化体积百分比（PAV）和总粥样硬化体积（TAV）]以及MACE。
在多变量倾向加权分析中，包括控制基线和同时进行的ACEI/ARB治疗以及阿利吉仑治疗持续时间，接受阿利吉仑治疗的非糖尿病患者表现出最大的PAV和TAV消退，而接受阿利吉仑治疗的糖尿病患者表现出最大的TAV进展和更大的PAV。与接受阿利吉仑治疗的糖尿病患者相比，接受阿利吉仑治疗的非糖尿病患者发生MACE的风险显著更低[风险比95%置信区间0.28（0.10，0.80）]。在PAV变化（p < 0.001）、TAV变化（p = 0.010）和MACE变化（p = 0.057）方面，均发现糖尿病状态与治疗分配之间存在统计学交互作用。
阿利吉仑在非糖尿病患者中似乎具有相对抗动脉粥样硬化作用。由于AQUARIUS研究中MACE数量有限且糖尿病患者数量较少，阿利吉仑在该人群中的促动脉粥样硬化作用尚无定论，因此这些结果应被视为提出假设。需要在非糖尿病患者中进行进一步的结局研究，以证实阿利吉仑可能的有益作用。
