Chest
Volume 139, Issue 1, January 2011, Pages 109-114
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Original Research
Pulmonary Vascular Disease
Safety and Efficacy of Ambrisentan for the Treatment of Portopulmonary Hypertension

https://doi.org/10.1378/chest.10-0574Get rights and content

Background

Ambrisentan is a selective endothelin-receptor antagonist that is approved by the US Food and Drug Administration for the treatment of pulmonary arterial hypertension. We describe hemodynamic responses and clinical outcomes of patients with portopulmonary hypertension (POPH) treated with ambrisentan.

Methods

In this observational study, we prospectively identified and followed consecutive adult patients with POPH who received monotherapy with ambrisentan ≤ 10 mg daily from January 2007 until December 2009. Liver enzymes were assessed monthly. Pulmonary hemodynamic responses were assessed using echocardiograms and right-sided heart catheterizations.

Results

We identified 13 patients (seven men) with POPH and began monotherapy with ambrisentan. The median age was 57 (interquartile range [IQR], 52-60). Patients were followed for a median of 613 days (IQR, 385-1,011). The median model for end-stage liver disease score was 10 (IQR, 8.5-15); eight patients had Child-Turcotte-Pugh A classification. Median time on ambrisentan therapy was 390 days (IQR, 363-611). Two patients died, one of advanced hepatocellular carcinoma and one of septic shock following pneumonia. The mean pulmonary artery pressure decreased from a baseline median of 58 mm Hg (IQR, 37-63) to 41 mm Hg (IQR, 27-48) (P = .004). The pulmonary vascular resistance median was reduced from 445 dynes/s/cm5 (IQR, 329-834) to 174 dynes/s/cm5 (IQR, 121-361) (P = .008). There was no difference in the longitudinal analysis of liver function tests (aspartate aminotransferase, alanine aminotransferase, total bilirubin, and international normalized ratio) after 12 months of therapy. One patient underwent successful liver transplantation and normalized pulmonary hemodynamic responses after transplantation.

Conclusions

In this small cohort of patients with moderate to severe pulmonary hypertension in the setting of POPH, we have shown that ambrisentan monotherapy can significantly improve pulmonary hemodynamic responses without adverse effect on hepatic function.

Section snippets

Materials and Methods

The Mayo Clinic institutional review board approved the Pulmonary Vascular Complications of Liver Disease (PVCLD) data collection. We prospectively identified and followed consecutive adult (≥ 18 years old) patients with POPH evaluated at the Mayo Clinic from January 2007 to December 2009 who were treated with ambrisentan as monotherapy (group 1, World Health Organization [WHO] functional class 2 or 3). Three patients refused the suggested IV prostacyclin therapy; no patient seen during this

Results

During the observation period, we identified 13 patients with POPH who were started on ambrisentan as monotherapy. Baseline clinical characteristics of the cohort are described in Table 1. All patients were considered to have at least moderate POPH, with an mPAP > 35 mm Hg. The patients were followed for a median of 613 days (IQR, 385-1,011). One patient stopped the medication after 2 weeks of therapy because of bilateral periorbital bleeding, peripheral edema, and a weight gain of 8 pounds,

Discussion

This single-institution observational study demonstrates that monotherapy with ambrisentan is effective and safe for the treatment of patients with POPH, as evidenced by significant improvements in hemodynamic measurements (mPAP, PVR, and cardiac output), biomarkers (BNP), and symptoms (WHO functional class) with no deterioration in systemic BP, liver function test results, or renal function. Ambrisentan was well tolerated, with only one patient stopping the medication because of side effects

Acknowledgments

Author contributions: All authors have directly contributed to the content of this manuscript and reviewed the final version.

Dr Cartin-Ceba: wrote the manuscript.

Dr Swanson: helped draft all portions of the manuscript.

Dr Iyer: helped draft all portions of the manuscript.

Dr Wiesner: helped draft all portions of the manuscript.

Dr Krowka: designed the study and reviewed and revised the final manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential

References (22)

  • MJ Krowka et al.

    Hepatopulmonary syndrome and portopulmonary hypertension: a report of the multicenter liver transplant database

    Liver Transpl

    (2004)
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