Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to propranolol

Abstract

Objective Non-selective β-blockers or endoscopic band ligation (EBL) are recommended for primary prophylaxis of variceal bleeding in patients with oesophageal varices. Additional α-adrenergic blockade (as by carvedilol) may increase the number of patients with haemodynamic response (reduction in hepatic venous pressure gradient (HVPG) of ≥20% or to values <12 mm Hg). Design Patients with oesophageal varices undergoing measurement of HVPG before and under propranolol treatment (80-160 mg/day) were included. HVPG responders were kept on propranolol (PROP group), while non-responders were placed on carvedilol (6.25-50 mg/day). Carvedilol responders continued treatment (CARV group), while non-responders to carvedilol underwent EBL. The primary aim was to assess haemodynamic response rates to carvedilol in propranolol non-responders. Results 36% (37/104) of patients showed a HVPG response to propranolol. Among the propranolol nonresponders 56% (38/67) eventually achieved a haemodynamic response with carvedilol, while 44% (29/67) patients were finally treated with EBL. The decrease in HVPG was significantly greater with carvedilol (median 12.5 mg/day) than with propranolol (median 100 mg/day): −19±10% versus −12±11% ( p<0.001). During a 2 year follow-up bleeding rates for PROP were 11% versus CARV 5% versus EBL 25% ( p=0.0429). Fewer episodes of hepatic decompensation (PROP 38%/CARV 26% vs EBL 55%; p=0.0789) and significantly lower mortality (PROP 14%/CARV 11% vs EBL 31%; p=0.0455) were observed in haemodynamic responders compared to the EBL group. Conclusions Carvedilol leads to a significantly greater decrease in HVPG than propranolol. Using carvedilol for primary prophylaxis a substantial proportion of nonresponders to propranolol can achieve a haemodynamic response, which is associated with improved outcome with regard to prevention of variceal bleeding, hepatic decompensation and death.

Primary prophylaxis of variceal bleeding

“…Reiberger et al demonstrated that 56% patients who failed to achieve an adequate reduction in HVPG with propranolol achieved a response with Carvedilol, with remaining patients undergoing EVL. Patients receiving Carvedilol were found to have a significant reduction in bleeding rate, hepatic decompensation and death compared to patients receiving EVL [16]. Thus, Carvedilol (6.25 mg increasing to 12.5 mg oral daily) should be considered a first-line agent in the primary prophylaxis of AVB.…”

Przez wątrobę do serca. Aspekty praktyczne kardiomiopatii wątrobowej — przegląd piśmiennictwa

“…karwedilolu jest nie tylko dobrze tolerowane, ale i bardziej efektywne w obniżaniu ciśnienia wrotnego niż kuracja propranololem (80-100 mg/d. ), przy podobnym wpływie na systemowe ciśnienie tętnicze i częstość rytmu serca; zwiększenie dawki karwedilolu nie przynosi większych korzyści, jednocześnie narażając chorych na wystąpie-nie niekorzystnych działań ubocznych, to jest hipotensji i bradykardii [22]. Wiadomo, że podanie nieselektywnych antagonistów receptorów beta-adrenergicznych może redukować ciśnienie wrotne poniżej 12 mm Hg i tym samym zmniejszać częstość występowania krwawienia z żylaków przełyku i gastropatii wrotnej, dodatkowo skraca wydłużony odstęp QT i redukuje objawy zespołu hiperdynamicznego u chorych z marskością wątroby oraz zmniejsza częstość występowania poważnego powikłania marskości wątroby, jakim jest spontaniczne bakteryjne zapalenie otrzewnej.…”

Keeping high model for end‐stage liver disease score liver transplantation candidates alive

“…26 Although nonselective B-blockers (NSBB) such as nadolol or propranolol do not prevent the development of varices, they can effectively achieve primary and secondary variceal hemorrhage prophylaxis and are therefore the standard of care for prevention. 27 Some high MELD patients are candidates for NSBB; however, recent data have raised concerns about the risk of NSBB in patients with refractory ascites after SBP development, and those patients require banding to obliteration.…”