Division of Cardiovascular and Diabetes Medicine, Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, United Kingdom.
J Am Coll Cardiol. 2013 Mar 5;61(9):926-32. doi: 10.1016/j.jacc.2012.09.066.
This study sought to ascertain if high-dose allopurinol regresses left ventricular mass (LVM) in patients with ischemic heart disease (IHD).
LV hypertrophy (LVH) is common in patients with IHD including normotensive patients. Allopurinol, a xanthine oxidase inhibitor, has been shown to reduce LV afterload in IHD and may therefore also regress LVH.
A randomized, double-blind, placebo-controlled, parallel group study was conducted in 66 patients with IHD and LVH, comparing 600 mg/day allopurinol versus placebo therapy for 9 months. The primary outcome measure was change in LVM, assessed by cardiac magnetic resonance imaging (CMR). Secondary outcome measures were changes in LV volumes by CMR, changes in endothelial function by flow-mediated dilation (FMD), and arterial stiffness by applanation tonometry.
Compared to placebo, allopurinol significantly reduced LVM (allopurinol -5.2 ± 5.8 g vs. placebo -1.3 ± 4.48 g; p = 0.007) and LVM index (LVMI) (allopurinol -2.2 ± 2.78 g/m(2) vs. placebo -0.53 ± 2.5 g/m(2); p = 0.023). The absolute mean difference between groups for change in LVM and LVMI was -3.89 g (95% confidence interval: -1.1 to -6.7) and -1.67 g/m(2) (95% confidence interval: -0.23 to -3.1), respectively. Allopurinol also reduced LV end-systolic volume (allopurinol -2.81 ± 7.8 mls vs. placebo +1.3 ± 7.22 mls; p = 0.047), improved FMD (allopurinol +0.82 ± 1.8% vs. placebo -0.69 ± 2.8%; p = 0.017) and augmentation index (allopurinol -2.8 ± 5.1% vs. placebo +0.9 ± 7%; p = 0.02).
High-dose allopurinol regresses LVH, reduces LV end-systolic volume, and improves endothelial function in patients with IHD and LVH. This raises the possibility that allopurinol might reduce future cardiovascular events and mortality in these patients. (Does a Drug Allopurinol Reduce Heart Muscle Mass and Improve Blood Vessel Function in Patients With Normal Blood Pressure and Stable Angina?; ISRCTN73579730).
本研究旨在确定高剂量别嘌醇是否能使缺血性心脏病(IHD)患者的左心室质量(LVM)消退。
LV 肥厚(LVH)在包括血压正常的 IHD 患者中很常见。别嘌醇,一种黄嘌呤氧化酶抑制剂,已被证明可降低 IHD 中的 LV 后负荷,因此也可能使 LVH 消退。
在 66 例 IHD 和 LVH 患者中进行了一项随机、双盲、安慰剂对照、平行组研究,比较了每天 600 毫克别嘌醇与安慰剂治疗 9 个月。主要观察指标为心脏磁共振成像(CMR)评估的 LVM 变化。次要观察指标为 CMR 评估的 LV 容积变化、血流介导的扩张(FMD)评估的内皮功能变化和平板测压评估的动脉僵硬度变化。
与安慰剂相比,别嘌醇可显著降低 LVM(别嘌醇-5.2 ± 5.8 g 比安慰剂-1.3 ± 4.48 g;p = 0.007)和 LVMI(别嘌醇-2.2 ± 2.78 g/m2 比安慰剂-0.53 ± 2.5 g/m2;p = 0.023)。两组间 LVM 和 LVMI 变化的绝对平均差异分别为-3.89 g(95%置信区间:-1.1 至-6.7)和-1.67 g/m2(95%置信区间:-0.23 至-3.1)。别嘌醇还可降低 LV 收缩末期容积(别嘌醇-2.81 ± 7.8 mls 比安慰剂+1.3 ± 7.22 mls;p = 0.047),改善 FMD(别嘌醇+0.82 ± 1.8% 比安慰剂-0.69 ± 2.8%;p = 0.017)和增强指数(别嘌醇-2.8 ± 5.1% 比安慰剂+0.9 ± 7%;p = 0.02)。
高剂量别嘌醇可使 IHD 和 LVH 患者的 LVH 消退,降低 LV 收缩末期容积,改善内皮功能。这提示别嘌醇可能降低这些患者未来的心血管事件和死亡率。(别嘌醇是否降低血压正常和稳定型心绞痛患者的心肌质量并改善血管功能?;ISRCTN73579730)。