Published online Nov 6, 2018. doi: 10.12998/wjcc.v6.i13.611
Peer-review started: July 23, 2018
First decision: August 25, 2018
Revised: September 3, 2018
Accepted: October 9, 2018
Article in press: October 9, 2018
Published online: November 6, 2018
Processing time: 107 Days and 19.6 Hours
Traditional nonselective beta-blockers (NSBBs) (i.e. propranolol and nadolol) and carvedilol are valid first-line treatments in patients starting primary prophylaxis of variceal bleeding. Although no clinical trial has adequately compared their efficacy head-to-head, several randomized controlled trials and a meta-analysis have shown that carvedilol is more effective in reducing portal pressure. NSBB-induced reductions in hepatic venous pressure gradient (HVPG) > 10% from baseline have been associated with a lower risk of decompensation and death. The acute hemodynamic test (i.e. HVPG response after 20 min of the intravenous injection of 0.15 mg/kg propranolol) has been proposed as a valid and more cost-effective alternative to separate HVPG procedures. Supporting this notion, recent studies in patients treated with traditional NSBB showed that the risk of decompensation was lower in those who had an acute response than in those who were acute nonresponders. The acute test also predicted the chronic hemodynamic response.
Since the acute test enables the earlier identification of chronic nonresponders to traditional NSBB and carvedilol has a greater efficacy for reducing portal pressure, this test could guide the type of NSBB to be used in patients starting primary prophylaxis of variceal bleeding.
The primary endpoint was development of first or further decompensation of cirrhosis. Secondary endpoints included death from any cause, association between acute and chronic hemodynamic response, and baseline clinical and laboratory variables related to the acute hemodynamic response.
We retrospectively reviewed all patients starting primary prophylaxis of variceal bleeding following an acute hemodynamic response-guided protocol. Acute or chronic hemodynamic response was defined as a decrease in HVPG to < 12 mmHg or as a ≥ 10% reduction in HVPG from baseline. According to our institutional protocol, 52 acute responders to intravenous propranolol were treated with traditional NSBB (i.e. propranolol or nadolol) and 24 acute nonresponders received carvedilol. A second hemodynamic study was performed in 27 and 13 patients, respectively. Follow-up data (i.e. medical history, laboratory values, imaging tests and treatment compliance) were recorded in each visit (i.e. within 1 mo after the performance of the baseline hemodynamic study, and every 3-6 mo thereafter).
The risk of first or further decompensation was similar in both groups at 1, 2 and 3 years of follow-up. A previous episode of hepatic encephalopathy was the only independent predictor of decompensation. Mortality rates were also similar between groups. No clinical, laboratory, or endoscopic variables at baseline were able to predict neither the acute nor the chronic hemodynamic response. A high proportion of acute nonresponders (69.2%) achieved a chronic hemodynamic response with carvedilol and there was a strong correlation between the acute and chronic changes in HVPG in the traditional NSBB group.
The early identification of acute nonresponders and their treatment with carvedilol resulted in risks of decompensation and death that were comparable to those of acute responders treated with propranolol. These findings suggest that carvedilol improved the long-term outcome of acute nonresponders, presumably by its greater effects on reducing portal pressure, and should be the preferred choice over NSBB for primary prophylaxis of variceal bleeding when hemodynamic testing is not available.
The design of our study cannot definitively conclude that carvedilol should become the beta-blocker of choice in patients starting primary prophylaxis of variceal bleeding. In order to confirm this possibility, a randomized controlled trial with a control group of acute nonresponders treated with traditional NSBB would be needed.