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Carvedilol vs Conventional Nonselective Beta Blockers for Secondary Prophylaxis of Variceal Bleeding
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- This study looked at the efficacy of carvedilol versus traditional nonselective beta blockers (propranolol) in secondary prophylaxis of esophageal variceal bleeding. A total of 87 patients were included in the analysis. The decrease in hepatic venous pressure gradient measures was greater in the carvedilol group compared with the traditional nonselective beta-blocker group. In addition, liver-related mortality and rebleeding rates were significantly lower in the carvedilol group.
- These findings suggest that carvedilol should be the nonselective beta blocker of choice for secondary prophylaxis of esophageal variceal bleeding.
abstract
This abstract is available on the publisher's site.
Access this abstract now Full Text Available for ClinicalKey SubscribersBACKGROUND & AIMS
Carvedilol induces stronger decreases in hepatic venous pressure gradient (HVPG) than conventional nonselective β-blockers (ie, propranolol). Limited data exist on the efficacy of carvedilol in secondary prophylaxis of variceal bleeding.
METHODS
Patients undergoing paired HVPG measurements for guiding secondary prophylaxis with either carvedilol or propranolol were included in this retrospective analysis. All patients also underwent band ligation. Changes in HVPG and systemic hemodynamics were compared between the 2 groups. Long-term follow-up data on rebleeding, acute kidney injury, nonbleeding decompensation, and liver-related death were analyzed applying competing risk regression.
RESULTS
Eighty-seven patients (carvedilol/propranolol, n = 45/42) were included in our study. The median baseline HVPG was 21 mm Hg (interquartile range, 18-24 mm Hg), and 39.1%/48.3%/12.6% had Child-Turcotte-Pugh A/B/C cirrhosis, respectively. Upon nonselective β-blocker initiation, HVPG decreased more strongly in carvedilol users (median relative decrease, -20% [interquartile range: -29% to -10%] vs -11% [-22% to -5%] for propranolol; P = .027), who also achieved chronic HVPG response more often (53.3% vs 28.6%; P = .034). Cumulative incidences for rebleeding (Gray test, P = .027) and liver-related death (P = .036) were significantly lower in patients taking carvedilol compared with propranolol. Notably, ascites development/worsening also was observed less commonly in carvedilol patients (P = .012). Meanwhile, acute kidney injury rates did not differ between the 2 groups (P = .255). Stratifying patients by HVPG response status yielded similar results. The prognostic value of carvedilol intake was confirmed in competing risk regression models.
CONCLUSIONS
Carvedilol induces more marked reductions in HVPG than propranolol in secondary prophylaxis of variceal bleeding, and thus is associated with lower rates of rebleeding, liver-related death, and further nonbleeding decompensation.
Additional Info
Carvedilol Achieves Higher Hemodynamic Response and Lower Rebleeding Rates Than Propranolol in Secondary Prophylaxis
Clin. Gastroenterol. Hepatol. 2023 Aug 01;21(9)2318-2326.e7, M Jachs, L Hartl, B Simbrunner, D Bauer, R Paternostro, L Balcar, B Hofer, N Pfisterer, M Schwarz, B Scheiner, AF Stättermayer, M Pinter, M Trauner, M Mandorfer, T ReibergerFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Carvedilol, a third-generation nonselective betablocker (NSBB), is more powerful than propranolol in reducing portal pressure (assessed by hepatic venous pressure gradient [HVPG]). High-quality evidence from RCTs and meta-analyses showed that in primary prophylaxis carvedilol improved clinical outcomes, including preventing decompensation, ascites, and bleeding, while enhancing survival.1 Baveno VII recommendations indicate that carvedilol, used at low doses (6.25–12.5 mg/day) to avoid hypotension, is the preferred NSBB in patients with compensated cirrhosis with signs of portal hypertension.2
However, carvedilol is not yet formally recommended for secondary prevention of recurrent complications from portal hypertension mainly owing to the fear of aggravating sodium retention in patients with ascites, through decreased arterial blood pressure with high doses (25–50 mg/day). Of note, RCTs on primary prophylaxis showed carvedilol to be effective and safe, not causing more adverse effects in the subgroup of patients with ascites, suggesting that it may also be used safely in secondary prophylaxis.
In the absence of large RCTs (probably related to high cost and industry disinterest), most available evidence derives from carefully conducted retrospective studies, like that by Jachs et al in Clinical Gastroenterology and Hepatology comparing carvedilol with propranolol (both associated with endoscopic band ligation). Their study confirms that carvedilol has advantages over propranolol in secondary prophylaxis, determining a greater reduction of HVPG and better clinical efficacy, both in terms of lower risk of recurrent bleeding and of new or worsening ascites, and improved survival. The study has limitations owing to its retrospective nature; however, taking it together with all available evidence, it strongly supports extending the use of low-dose carvedilol for the prevention of recurrent complications from portal hypertension in cirrhosis. Still, further safety data are needed in patients with refractory ascites.
References
1. Reiberger T, Ulbrich G, Ferlitsch A, et al. Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to propranolol. Gut. 2013;62(11):1634-1641. https://gut.bmj.com/content/62/11/1634
2. de Franchis R, Bosch J, Garcia-Tsao G, et al. Baveno VII - Renewing consensus in portal hypertension. J Hepatol. 2022;76(4):959-974. https://www.sciencedirect.com/science/article/pii/S0168827821022996