Table 2.
Proportion of patients with small varices in studies evaluating non-selective betablocker therapy
| Author, journal, year | Design |
N patients overall N with small EV (%) |
NSBB (dose) | HVPG measurement | Main conclusions |
|---|---|---|---|---|---|
| The PROVA Study Group, Hepatology, 1991 [70] | RCT | 286/166 (58%) | Propranolol (160–400 mg/day) | No | • Small EV had a considerable risk of bleeding • The incidence of variceal hemorrhage and overall mortality was not significantly different between patients receiving NSBB, sclerotherapy or combination therapy |
| Calès, Eur J Gastroenterol Hepatol, 1999{Cales, 1999 #1480} | RCT | 206/127 (62%) | Propranolol (160 mg) | No | • NSBB therapy did neither prevent occurrence/growth of EV or variceal bleeding and did not reduce mortality in patients without/with small EV |
| Merkel, Hepatology, 2000 [71] | RCT | 146/6 (4.1%) | Nadolol (40–160 mg/day) | No | • NSBB plus ISMN was more effective than NSBB alone in the long-term prophylaxis of first variceal bleeding |
| Merkel, Hepatology, 2000 [72] | RCT | 49/2 (4.1%) | Nadolol (40–80 mg/day) | Yes (all) | • HVPG reponse was the best predictor of efficacy in patients receiving NSBB or NSBB plus ISMN for primary prophylaxis |
| Abraczinskas, Hepatology, 2001 [73] | RCT | 49/32 (65.3%) | Propranolol (dose not specified) | No | • NSBB therapy in small and large EV is effective in preventing of first variceal bleeding • After discontinuation of NSBB therapy, the risk of variceal bleeding persisted |
| Merkel, Gastroenterology, 2004 [7] | RCT | 161 (100%) | Nadolol (mean dose 62 ± 25 mg/day) | Yes (11.8%) | • Primary prophylaxis with NSBB should be considered in patients with small EV • NSBB delay the growth of small EV |
| Turnes, Am J Gastroenterol, 2006 [74] | RCT | 71/4 (6.6%) | Propranolol (54 ± 14 to 79 ± 12 mg/day) | Yes (all) | • Positive impact of HVPG response in the setting of primary prophylaxis • Insufficient data on patients with small EV |
| Reiberger, Gut, 2013 [75] | Non-randomized clinical trial | 104/41 (39.4%) | Propranolol (80–160 mg/day) Carvedilol (6.25–50 mg/day) |
Yes (all) | • Carvedilol induces HVPG response in a considerable proportion of patients with propranolol non-response • Patients with small EV were included and also benefited from hemodynamic response to carvedilol |
| Sarin, Hepatol Int, 2013 [8] | RCT | 150 (100%) | Propranolol (40 mg/day followed by dose titration) | Yes (66%) | • NSBB therapy did neither prevent growth of EV or variceal bleeding and did not reduce mortality in patients with small EV |
| Je, Clin Mol Hepatol, 2014 [76] | Retrospective study | 504/92 (18.3%) | Propanolol (20 mg/day followed by dose titration) | No | • NSBB plus EBL was more effective than NSBB alone in primary prophylaxis • However, EBL was performed only in patients with large EV |
| Bhardwaj, Gut, 2016 [77] | RCT | 70 (100%) | Carvedilol (mean dose 12 ± 1.67 mg/day) | Yes (all) | • Reduction of progression to large EV |
| Kim, Dig Dis Sci, 2016 [78] | Retrospective study | 898/775 (86.3%) | 48.6% of 898 patients were on NSBB therapy | No | • Variceal bleeding was a risk factor for mortality in patients with hepatocellular carcinoma |
| Pfisterer, Aliment Pharmacol Ther, 2018 [1] | Retrospective study | Primary prophylaxis: 281/48 (17.1%) |
Propranolol (median dose 40 mg/day) Carvedilol (median dose 12.5 mg/day) |
No | • Addition of EBL to NSBB therapy did not further reduce the risk of first variceal bleeding or mortality • Patients receiving HVPG-guided primary prophylaxis (including patients with small EV) tended to have a better prognosis than patients receiving non-HVPG-guided NSBB therapy or combination therapy |
EBL, endoscopic band ligation; EV, esophageal varices; HVPG, hepatic venous pressure gradient; NSBB, non-selective betablocker; RCT, randomized controlled trial