Carvedilol, probably the β-blocker of choice for everyone with cirrhosis and portal hypertension: But not so fast!

Abstract

Non-selective β-blockers (NSBBs) are the mainstay long-term therapy for portal hypertension. Numerous randomized-controlled trials and observational studies have established their therapeutic benefit in patients with cirrhosis.1 The efficacy of NSBBs is related to the lowering effect on portal-pressure, which decreases the risk of portal hypertension-related events, particularly variceal bleeding. NSBBs achieve the portal-pressure decreasing effect by reducing the splanchnic blood-flow through a decrease in cardiac-output induced by the β-1 adrenergic blockade and, mainly, because of a splanchnic vasoconstriction induced by an unopposed α-adrenergic activity achieved by the β-2 adrenergic blockade.2 Carvedilol, is a potent NSBB that also antagonizes α-1-adrenergic receptors.2, 3 This activity confers to carvedilol, in addition to its NSBB-effect, intrinsic vasodilatory activity and thus the ability to reduce the increased hepatic resistance that is the first mechanism leading to portal hypertension in cirrhosis.4 However, the vasodilatory activity of carvedilol is not liver selective and also affects the systemic circulation, with potential to reduce arterial pressure. This issue of Liver International publishes a review by Turco et al, nicely detailing the effect of carvedilol on portal hypertension in cirrhosis.3 The paper elegantly summarizes the evidence to suggest that carvedilol can be the NSBBs of choice in cirrhosis. However, some considerations may be useful to precisely quantify this otherwise feasible suggestion.