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Hemodynamic Response to Carvedilol is Maintained for Long Periods and Leads to Better Clinical Outcome in Cirrhosis: A Prospective Study.
J Clin Exp Hepatol 2016; 6(3):175-185JC

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.

Authors+Show Affiliations

Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, New Delhi, India.Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, New Delhi, India.Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, New Delhi, India.Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, New Delhi, India.Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, New Delhi, India.Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, New Delhi, India.Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, New Delhi, India.Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, New Delhi, India.Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, New Delhi, India.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27746613

Citation

Kirnake, Vijendra, et al. "Hemodynamic Response to Carvedilol Is Maintained for Long Periods and Leads to Better Clinical Outcome in Cirrhosis: a Prospective Study." Journal of Clinical and Experimental Hepatology, vol. 6, no. 3, 2016, pp. 175-185.
Kirnake V, Arora A, Gupta V, et al. Hemodynamic Response to Carvedilol is Maintained for Long Periods and Leads to Better Clinical Outcome in Cirrhosis: A Prospective Study. J Clin Exp Hepatol. 2016;6(3):175-185.
Kirnake, V., Arora, A., Gupta, V., Sharma, P., Singla, V., Bansal, N., ... Kumar, A. (2016). Hemodynamic Response to Carvedilol is Maintained for Long Periods and Leads to Better Clinical Outcome in Cirrhosis: A Prospective Study. Journal of Clinical and Experimental Hepatology, 6(3), pp. 175-185.
Kirnake V, et al. Hemodynamic Response to Carvedilol Is Maintained for Long Periods and Leads to Better Clinical Outcome in Cirrhosis: a Prospective Study. J Clin Exp Hepatol. 2016;6(3):175-185. PubMed PMID: 27746613.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hemodynamic Response to Carvedilol is Maintained for Long Periods and Leads to Better Clinical Outcome in Cirrhosis: A Prospective Study. AU - Kirnake,Vijendra, AU - Arora,Anil, AU - Gupta,Varun, AU - Sharma,Praveen, AU - Singla,Vikas, AU - Bansal,Naresh, AU - Goyal,Mohan, AU - Chawlani,Romesh, AU - Kumar,Ashish, Y1 - 2016/01/23/ PY - 2015/07/23/received PY - 2016/01/15/accepted PY - 2016/10/18/entrez PY - 2016/10/18/pubmed PY - 2016/10/18/medline KW - CTP, Child-Turcotte-Pugh KW - EVL, endoscopic variceal ligation KW - FHVP, free hepatic venous pressure KW - HVPG KW - HVPG, hepatic venous pressure gradient KW - MELD, model for end-stage liver disease KW - NSBB, non-selective beta-blocker KW - VBL, variceal band ligation KW - WHVP, wedged hepatic venous pressure KW - carvedilol KW - cirrhosis KW - esophageal varices KW - portal hypertension SP - 175 EP - 185 JF - Journal of clinical and experimental hepatology JO - J Clin Exp Hepatol VL - 6 IS - 3 N2 - 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. SN - 0973-6883 UR - https://www.unboundmedicine.com/medline/citation/27746613/Hemodynamic_Response_to_Carvedilol_is_Maintained_for_Long_Periods_and_Leads_to_Better_Clinical_Outcome_in_Cirrhosis:_A_Prospective_Study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0973-6883(16)00011-6 DB - PRIME DP - Unbound Medicine ER -