Carvedilol versus Propranolol for Primary Prophylaxis of Variceal Bleeding in Cirrhosis: An Open-Label Randomised Controlled Trial

Abstract

Background: Non-selective beta-blockers are the cornerstone of primary prophylaxis of variceal bleeding in cirrhosis. Carvedilol, which adds anti-alpha-1 adrenergic activity to nonselective beta-blockade, lowers portal pressure more effectively than propranolol, but direct comparative data in primary prophylaxis remain limited, particularly from Indian cohorts. Methods: An open-label randomised controlled trial was conducted at a tertiary care centre during 2025. One hundred and twenty-four adults with cirrhosis and grade II to IV oesophageal varices without previous haemorrhage were randomised 1:1 to carvedilol or propranolol (62 per arm) with concealed allocation. Hepatic venous pressure gradient (HVPG) was measured at baseline and six months. The primary outcome was haemodynamic response, defined as an HVPG fall of at least 20 per cent from baseline or to below 12 mmHg. Secondary outcomes were bleeding, decompensation, mortality and adverse events. Analysis was by intention to treat. Results: Baseline characteristics were comparable. Haemodynamic response occurred in 35 patients (56.5 per cent) on carvedilol versus 20 (32.3 per cent) on propranolol (p=0.007). Mean HVPG reduction was greater with carvedilol (19.4 +/- 6.8 versus 12.1 +/- 6.2, p<0.001). Variceal bleeding occurred in 4 (6.5 per cent) versus 10 patients (16.1 per cent) (hazard ratio 0.38, 95 per cent CI 0.12 to 1.22, p=0.086). Symptomatic hypotension was commoner with carvedilol (12.9 versus 3.2 per cent, p=0.048) and dyspnoea, bradycardia and fatigue with propranolol; discontinuation rates were similar. Conclusion: Carvedilol achieved a significantly higher haemodynamic response rate than propranolol with comparable tolerability, supporting its use as the preferred non-selective beta-blocker for primary prophylaxis, although the trial was not powered for bleeding endpoints.