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

https://doi.org/10.1016/j.jceh.2016.01.004Get rights and content

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.

Section snippets

Patients

This was a prospective study conducted in the Department of Gastroenterology at Sir Ganga Ram Hospital, New Delhi, India, between August 2011 and May 2013. The ethics committee of the hospital approved the study and a written informed consent was obtained from all the participants. The study conformed to the Helsinki declaration of 1975 as revised in 1983.

Patients

Between August 2011 and December 2012, a total of 80 patients, in whom NSBB was indicated, were enrolled for the study. Eleven patients were excluded for following reasons: (i) Already on NSBBs at the time of HVPG (n = 6); (ii) grade 3–4 hepatic encephalopathy at the time of enrollment (n = 3); and (iii) systolic blood pressure <90 mm Hg at the time of HVPG (n = 2). Hence, remaining 69 patients were included in the study. The last included patient was followed till May 2013.

The baseline

Discussion

To summarize the results, our study showed that before beginning carvedilol therapy, acute hemodynamic response testing is a reliable method of predicting which patients are more likely to respond to carvedilol in long-term. In our study, the acute-hemodynamic-response was seen in 67% of patients and most (92%) of these acute responders maintained their response to carvedilol over long-term (6 months). In addition, carvedilol therapy led to better clinical outcome in these patients compared to

Authors’ Contribution

Study design, supervision – AA, AK, PS.

Patient enrollment, data collection – VK, VG, MG, RC.

Data analysis, statistics – AK.

Drafting of manuscript – VK, AK.

Critical revision for important intellectual content – PS, VS, NB.

Conflicts of Interest

The authors have none to declare.

Acknowledgements

This study did not receive any external funding.

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