Hemodynamic Response to Carvedilol is Maintained for Long Periods and Leads to Better Clinical Outcome in Cirrhosis: A Prospective Study

Abstract

Background: Non-selective beta-blockers (NSBBs), e.g. propranolol, are recommended for prophylaxis of variceal bleeding in cirrhosis. Carvedilol, a newer NSBB with additional anti-α1-adrenergic activity, is superior to propranolol in reducing portal pressure. Repeated HVPG measurements are required to identify responders to NSBB. We aimed to determine whether a single-time HVPG measurement, using acute-hemodynamic-response-testing, is sufficient to predict long-term response to carvedilol, and whether these responders have better clinical outcome.

Methods: Consecutive patients with cirrhosis, aged 18-70 years, in whom NSBB was indicated for primary/secondary prophylaxis of variceal bleeding, and who underwent HVPG were included. Acute-hemodynamic-response was defined as a decrease in HVPG ≥10% from baseline or absolute HVPG value declining to <12 mm Hg, 1 h after 25 mg oral carvedilol. The aims of the study were to determine: the proportion of patients who achieved acute-hemodynamic-response to carvedilol; whether HVPG-response is maintained for 6 months; and clinical outcome of acute-responders to carvedilol therapy for 6 months.

Results: The study included 69 patients (median age 51, males 93%). Alcohol was the most common etiology; 59% patients belonged to Child-Pugh class B. NSBB was indicated for primary prophylaxis in 36% and secondary prophylaxis in 64% patients. According to the response criteria, 67% patients were found to be acute-hemodynamic-responders. At 6 months, 92% patients were found to be still maintaining their hemodynamic response to carvedilol. Using intention-to-treat analysis, 76% patients maintained their response. These acute responders, on chronic treatment with carvedilol during the 6-month period, had lesser episodes of variceal bleeding, better ascites control, and improved MELD and CTP scores, than non-carvedilol treated non-responders. However, survival remained similar in both the groups.

Conclusions: A single-time HVPG measurement with acute-hemodynamic-response-testing is simple and reliable method for identifying patients who are more likely to respond to carvedilol therapy. The HVPG-response is maintained over a long period in majority of these patients and carvedilol therapy leads to better clinical outcome in these patients.

Keywords: CTP, Child-Turcotte-Pugh; EVL, endoscopic variceal ligation; FHVP, free hepatic venous pressure; HVPG; HVPG, hepatic venous pressure gradient; MELD, model for end-stage liver disease; NSBB, non-selective beta-blocker; VBL, variceal band ligation; WHVP, wedged hepatic venous pressure; carvedilol; cirrhosis; esophageal varices; portal hypertension.

Figure 1

Study design.

Figure 2

Subgroup analysis data for variceal bleeding, stratified according to primary and secondary prophylaxis. (Note: There was no statistically significant difference between the four outcome groups, mainly due to small number of patients in each group.)

Figure 3

Median HVPG in patients who were acute-hemodynamic-responders (n = 46) and in whom HVPG was repeated at 6 months (n = 38). The HVPG response was maintained at 6 months in most patients. Legend: *P < 0.01 compared to baseline; **P < 0.01 compared to baseline.