Effects of candesartan and propranolol combination therapy versus propranolol monotherapy in reducing portal hypertension.
Effects of candesartan and propranolol combination therapy versus propranolol monotherapy in reducing portal hypertension.
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DOI：
10.3350/cmh.2014.20.4.376
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发表时间：
2014-12
影响因子：
8.9
通讯作者：
Kim MY
中科院分区：
文献类型：
--
作者：
Kim JH;Kim JM;Cho YZ;Na JH;Kim HS;Kim HA;Kang HW;Baik SK;Kwon SO;Cha SH;Kim YJ;Kim MY
血管紧张素受体阻滞剂（ARB）抑制激活的肝星状细胞收缩，并被认为是减少肝内阻力的动态部分。本研究在一项前瞻性、随机对照试验中比较了ARB坎地沙坦和普萘洛尔联合治疗与普萘洛尔单药治疗对肝硬化患者门静脉压力的影响。2008年1月至2009年7月，53例具有临床意义的门静脉高压症患者随机接受坎地沙坦和普萘洛尔联合治疗（26例患者）或普萘洛尔单药治疗（27例患者）。在计划药物给药前和给药后3个月，评估两组的肝静脉压差（HVPG）。普萘洛尔的剂量随后从20 mg bid增加至达到目标心率，坎地沙坦的剂量固定为8 mg qd。主要终点是HVPG应答率; HVPG降低>基线值的20%或<12 mmHg的患者被定义为应答者。两组平均门静脉压均显著下降，联合用药组从16 mmHg（范围，12-28 mmHg）降至13.5 mmHg（范围，6-20 mmHg）（P<0.05），普萘洛尔单药组从17 mmHg（范围，12-27 mmHg）降至14 mmHg（范围，7-25 mmHg）（P<0.05）。然而，两组之间药物诱导的压力降低无显著差异[3.5 mmHg（范围，-3-11 mmHg）vs. 3 mmHg（范围，-8-10 mmHg），P=0.674]。联合治疗组和单药治疗组的缓解率（55.6% vs. 61.5%，P=0.435）和平均血压或心率降低也无显著差异。在普萘洛尔基础上加用坎地沙坦（一种ARB）治疗门静脉高压症，与普萘洛尔单药治疗相比，没有获益，因此不推荐使用。
Angiotensin receptor blockers (ARBs) inhibit activated hepatic stellate cell contraction and are thought to reduce the dynamic portion of intrahepatic resistance. This study compared the effects of combined treatment using the ARB candesartan and propranolol versus propranolol monotherapy on portal pressure in patients with cirrhosis in a prospective, randomized controlled trial. Between January 2008 and July 2009, 53 cirrhotic patients with clinically significant portal hypertension were randomized to receive either candesartan and propranolol combination therapy (26 patients) or propranolol monotherapy (27 patients). Before and 3 months after the administration of the planned medication, the hepatic venous pressure gradient (HVPG) was assessed in both groups. The dose of propranolol was subsequently increased from 20 mg bid until the target heart rate was reached, and the candesartan dose was fixed at 8 mg qd. The primary endpoint was the HVPG response rate; patients with an HVPG reduction of >20% of the baseline value or to <12 mmHg were defined as responders. The mean portal pressure declined significantly in both groups, from 16 mmHg (range, 12-28 mmHg) to 13.5 mmHg (range, 6-20 mmHg) in the combination group (P<0.05), and from 17 mmHg (range, 12-27 mmHg) to 14 mmHg (range, 7-25 mmHg) in the propranolol monotherapy group (P<0.05). However, the medication-induced pressure reduction did not differ significantly between the two groups [3.5 mmHg (range, -3-11 mmHg) vs. 3 mmHg (range, -8-10 mmHg), P=0.674]. The response rate (55.6% vs. 61.5%, P=0.435) and the reductions in mean blood pressure or heart rate also did not differ significantly between the combination and monotherapy groups. The addition of candesartan (an ARB) to propranolol confers no benefit relative to classical propranolol monotherapy for the treatment of portal hypertension, and is thus not recommended.