Inappropriate use of nonselective β-Blockers
In recent years, there has been intense debate about the therapeutic window for nonselective β-blockers (NSBBs) in patients with liver cirrhosis.14,15 Consequently, many physicians are uncertain about the appropriate use of NSBBs, while clear treatment algorithms are often lacking. Issues in this setting include stopping indicated NSBB treatment because of exaggerated safety concerns or giving the wrong dosage and/or type of NSBB.
In general, NSBBs can be considered safe and are associated with improved outcomes in patients with significant portal hypertension.14 They have been associated with a lower rate of hepatic decompensation, which is suggested to decrease the incidence of SBP, while they have also been shown to reduce the risk of variceal bleeding and to be linked to improved survival.16–19 At present, their only established treatment indications remain primary and secondary prophylaxis of variceal bleeding.2 However, a prospective randomized trial has demonstrated beneficial effects of NSBBs for patients who have portal hypertension even in the absence of varices.20
Propanolol and carvedilol are the most widely used NSBBs in patients with cirrhosis. Unlike propranolol, carvedilol inhibits a1-signaling and is considered to be more effective at lowering portal pressure.21,22 The higher efficacy of carvedilol might, however, be accompanied by more pronounced lowering of systemic blood pressure and, theoretically, the potential to impair renal blood supply.21
General safety concerns raised regarding the use of any NSBB in patients with advanced stages of cirrhosis, as indicated by refractory ascites and/or SBP,23,24 have not been confirmed by other studies and may be related to high NSBB doses and/or a poor haemodynamic status.19,25–27 In one study of patients with SBP, only a high dose (180 mg/d) of NSBB decreased survival, whereas a low dose (80 mg/d) improved survival.25 In our own cohort, a low dose of NSBB was associated with improved survival of patients with decompensated liver cirrhosis and ascites, regardless of the presence of SBP or acute-on-chronic liver failure (ACLF) unless the patient suffered from severe hypotension (mean arterial pressure [MAP] <65 mmHg and/or systolic arterial pressure <90 mmHg).19
In our opinion, several factors (including the stage of liver disease) should be considered for safe use of NSBBs. Patients who have advanced cirrhosis and ascites and/or are at risk of hepatorenal syndrome might be better treated with propranolol first. In general, low doses of carvedilol and propranolol should be preferred for those with advanced cirrhosis as both drugs are metabolized in the liver—higher doses may lead to accumulation and adverse systemic effects. Using more than 80 mg/d of propranolol is not recommended (i.e. in those with refractory ascites).2 In patients at high risk of variceal bleeding but with preserved liver function carvedilol might be the better treatment choice.
Deciding when to discontinue an NSBB might be better based on haemodynamic status and/or signs of adverse effects (e.g. renal impairment and/or hypotension) rather than a clinical status such as ascites or SBP (figure 1). Taking a cautious approach regarding the NSBB dose is supported by other studies. One study with a propensity matched cohort reported increased survival in patients with therapy-refractory ascites who were taking an NSBB. Another study reported increased survival in patients with liver cirrhosis and ACLF who were taking an NSBB. Both studies used relatively low NSBB doses within their cohorts.26,27
Figure 1 | Discontinuation of nonselective β-blockers. Hemodynamic status and/or signs of adverse effects (e.g. renal impairment and/or hypotension) might be better used to decide when to discontinue nonselective β-blockers, rather than clinical status (e.g. ascites or SBP). AKI, acute kidney injury; MAP, mean arterial pressure.
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