Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
J Nucl Med. 2013 Oct;54(10):1733-9. doi: 10.2967/jnumed.113.120477. Epub 2013 Aug 22.
Carvedilol, a nonselective β-blocker, may be more effective than the selective β-blocker metoprolol in reducing the risk of thromboembolic events in heart failure. The aim of this study was, first, to assess whether there is a differential response in cardiac sympathetic activity by (123)I-meta-iodobenzylguanidine ((123)I-MIBG) imaging when either β-blocker is used. Second, we assessed whether that response correlates with levels of various serum factors that serve as markers for coagulability.
In this prospective, randomized, open-label crossover study with masked outcome assessments, stable heart failure patients (left ventricular ejection fraction < 40%) homozygous for the Arg16/Gln27 (n = 13) or Gly16/Glu27 haplotype (n = 8) of the β2-receptor were randomized to equipotent dosages of carvedilol or metoprolol for two 6-wk periods. Primary outcome was sympathetic activity as measured by (123)I-MIBG myocardial washout. Secondary outcomes included markers of hemostasis.
(123)I-MIBG cardiac washout was lower during carvedilol than metoprolol treatment (12.9% ± 3.9% vs. 22.1% ± 2.8%, respectively, P = 0.003), irrespective of β2-adrenergic receptor haplotype. In addition, treatment with carvedilol resulted in a lower von Willebrand factor than did metoprolol (149% ± 13% vs. 157% ± 13%, respectively, P = 0.01), irrespective of β2-adrenergic receptor haplotype.
Compared with metoprolol, carvedilol resulted in greater reduction of sympathetic activity after 6 wk of treatment and lower von Willebrand factor concentrations in both Arg16/Gln27 and Gly16/Glu27 individuals. Therefore, carvedilol may reduce the risk of thromboembolic events in patients with heart failure, irrespective of β2-receptor haplotype status.
本研究旨在：首先，通过（123）I-间碘苄胍（（123）I-MIBG）成像评估当使用β-受体阻滞剂时心脏交感神经活动是否存在差异反应；其次，评估该反应是否与各种作为凝血标志物的血清因子水平相关。
在这项前瞻性、随机、开放标签的交叉研究中，采用了双盲结果评估，稳定的心力衰竭患者（左心室射血分数<40%）为β2-受体的 Arg16/Gln27（n=13）或 Gly16/Glu27 单倍型（n=8）纯合子，随机分为两组，分别接受卡维地洛或美托洛尔等效剂量治疗 6 周。主要结局是通过（123）I-MIBG 心肌洗脱测量的交感神经活性。次要结局包括止血标志物。
卡维地洛治疗时（123）I-MIBG 心脏洗脱率低于美托洛尔治疗（分别为 12.9%±3.9%和 22.1%±2.8%，P=0.003），与β2-肾上腺素能受体单倍型无关。此外，与美托洛尔相比，卡维地洛治疗导致血管性血友病因子（von Willebrand factor）降低（分别为 149%±13%和 157%±13%，P=0.01），与β2-肾上腺素能受体单倍型无关。
与美托洛尔相比，卡维地洛在 6 周治疗后导致交感神经活性更大的降低，且 Arg16/Gln27 和 Gly16/Glu27 个体的血管性血友病因子浓度降低。因此，卡维地洛可降低心力衰竭患者的血栓栓塞事件风险，与β2-受体单倍型状态无关。
