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Safety and efficacy of ambrisentan for the treatment of portopulmonary hypertension.

AbstractBACKGROUND:
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/cm(5) (IQR, 329-834) to 174 dynes/s/cm(5) (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.
AuthorsRodrigo Cartin-Ceba, Karen Swanson, Vivek Iyer, Russell H Wiesner, Michael J Krowka
JournalChest (Chest) Vol. 139 Issue 1 Pg. 109-14 (Jan 2011) ISSN: 1931-3543 [Electronic] United States
PMID20705798 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Phenylpropionates
  • Pyridazines
  • ambrisentan
Topics
  • Administration, Oral
  • Cardiac Catheterization
  • Central Venous Pressure (drug effects)
  • Dose-Response Relationship, Drug
  • Echocardiography
  • Female
  • Follow-Up Studies
  • Humans
  • Hypertension, Portal (diagnosis, drug therapy, physiopathology)
  • Hypertension, Pulmonary (diagnosis, drug therapy, physiopathology)
  • Male
  • Middle Aged
  • Phenylpropionates (administration & dosage)
  • Prospective Studies
  • Pyridazines (administration & dosage)
  • Treatment Outcome

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