간경변증에서 식도정맥류출혈 예방을 위한 카베디롤, Carvedilol against variceal hemorrhage in patients with cirrhosis

간경변증에서 식도정맥류출혈 예방을 위한 카베디롤

(Carvedilol is an alternative to treatment with a nonselective beta blocker)

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1. 베타차단 효과에 더하여 경한 anti-alpha 1 adrenergic activity 효과가 있고 이것이 hepatic vascular tone과 hepatic resistance을 추가적으로 경감시킨다.

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2. Child A cirrhosis에서는 dose of 12.5 mg twice a day가 권고되고 Child B or C cirrhosis에서는 dose of 6.25 mg twice가 권고된다(투약을 견딜 수 있다면)

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3. 카베디롤은 GFR을 감소시키지 않으나 plasma volume 증가와 관련이 있으므로 이뇨제를 복용 중이지 않다면 추가적으로 필요할 수 있고, 이미 복용 중이라면 용량이 증가할 수도 있다.

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Carvedilol — Carvedilol is a potent beta blocker that also has mild anti-alpha 1 adrenergic activity. It is an alternative to nonselective beta blockers for routine prophylaxis. In addition to reducing portal venous inflow through nonselective beta blockade, the anti-alpha 1 adrenergic activity leads to reduced hepatic vascular tone and hepatic resistance. This in turn leads to a further reduction in portal pressure. However, it also can result in significant drops in mean arterial blood pressure (average decrease of 23 percent in one study), which may be poorly tolerated by patients with cirrhosis.

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The effect on HVPG appears to be greater in patients with Child B or C cirrhosis compared with patients with Child A cirrhosis, possibly due to changes in hepatic metabolism of the drug. For patients with Child A cirrhosis, a dose of 12.5 mg twice a day has been recommended, whereas a dose of 6.25 mg twice a day has been recommended for patients with Child B or C cirrhosis. Carvedilol does not decrease the glomerular filtration rate, but it is associated in with an increase in plasma volume. As a result, patients may require the addition of a diuretic or, for those already on a diuretic, an increase in the dose.

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Multiple studies of the hemodynamic effects of carvedilol suggest that carvedilol causes a dose-related decrease in HVPG of about 20 percent from baseline, which is significantly higher than is seen with propranolol. As an example, one study with 35 patients with cirrhosis found that the mean decrease in HVPG with carvedilol was 20 percent, compared with 13 percent for propranolol. In addition, significantly more patients treated with carvedilol attained an HVPG ≤12 mmHg compared with propranolol (64 versus 14 percent).

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In a trial of 140 patients with cirrhosis and small esophageal varices with 24 month follow-up, the rate of no progression to large varices was higher in patients receiving carvedilol compared with placebo (79 versus 61 percent). One patient receiving carvedilol developed symptomatic bradycardia and hypotension which resolved with discontinuation of the drug.

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Carvedilol has also been compared with EVL. In a randomized trial with 152 patient, carvedilol had lower rates of first variceal hemorrhage compared with EVL (10 versus 23 percent), and there was no difference in overall or hemorrhage-related mortality. In addition, six patients in the EVL group bled as a result of ulcers related to the banding. In a second randomized trial with 168 patients with varices, the rate of hemorrhage was similar for those who received carvedilol and those who underwent EVL (6.9 versus 8.5 percent), hemorrhage-related mortality (4.9 versus 4.6 percent), and overall mortality (20 versus 13 percent). Of note, one of the patients in the EVL group with bleeding bled from a banding-related esophageal ulcer.

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REF. UpToDate 2020.01.19