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Poster Presentations: Wednesday, October 26, 2011 |

Hepatic Transaminase Abnormalities in Pulmonary Arterial Hypertension: A Report From the REVEAL Registry FREE TO VIEW

David Badesch, MD; Harrison Farber, MD; Michael McGoon, MD; A. Frost, MD; C. Gregory Elliott, MD; Raymond Benza, MD; Abby Poms, BS; Dave Miller, MS; Robyn Barst, MD
Chest. 2011;140(4_MeetingAbstracts):737A. doi:10.1378/chest.1119558
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Abstract

PURPOSE: The Registry to EValuate Early And Long-term Pulmonary Arterial Hypertension (PAH) Disease Management (REVEAL), a 55-center observational, US study, examines current clinical practice in patients with PAH. We assessed aspartate transaminase/alanine transaminase (AST/ALT) elevation frequencies in patients by PAH-specific medication class, and by specific endothelin receptor antagonist (ERA) due to ERAs’ association with AST/ALT abnormalities.

METHODS: Enrollment closed December 2009 (N = 3518); datalock was March 4, 2011. Analyses were restricted to adult patients without portopulmonary hypertension. Medication class analyses were restricted to newly diagnosed, treatment-naïve patients initiating PAH-specific monotherapy. Drug-specific analyses were restricted to patients who were treatment-naïve to an ERA (and therefore included PAH-specific mono- and combination therapy). Freedom from elevations greater than upper limit of normal (>ULN) and >3 ULN were compared by log-rank test and Kaplan-Meier estimates; at-risk time was censored at time of any medication change for the class comparison or discontinuation of ERA for the ERA comparison.

RESULTS: At 24 months after initiating PAH-specific monotherapy, freedom from AST/ALT levels >ULN was 62 ± 6%, 70 ± 5%, and 74 ± 4% in patients started on a prostanoid (n = 146), an ERA (n = 145), or a phosphodiesterase-5 inhibitor (n = 220), respectively (P = 0.30); freedom from elevations >3 ULN was 88 ± 5%, 95 ± 2%, and 96 ± 1% (P = 0.19), respectively. For patients in whom bosentan or ambrisentan was started, as monotherapy or as add-on therapy, freedom from elevations at 24 months after ERA initiation was similar (P = 0.88, P = 0.34): for patients on bosentan (n = 278, >ULN: 69 ± 3%, >3ULN: 96 ± 1%); for patients on ambrisentan (n = 279, >ULN: 69 ± 3%, >3ULN: 98 ± 1%).

CONCLUSIONS: AST/ALT elevations occur in PAH regardless of medication class or specific ERA. This analysis does not demonstrate differences in frequency of transaminase elevations among these 3 drug classes or between specific ERAs. These data should be interpreted with caution given limitations of non-randomized observational registries. Specifically, comparisons may have been affected by differences in disease severity or etiology, limited sample sizes, and lack of requirement to perform specific tests after enrollment.

CLINICAL IMPLICATIONS: AST/ALT abnormalities occur in PAH regardless of PAH-specific therapy.

DISCLOSURE: David Badesch: Consultant fee, speaker bureau, advisory committee, etc.: Dr Badesch has received honoraria for service on Steering Committees and/or Advisory Boards for Actelion, Arena, Bayer, Ikaria, Gilead, Encysive Pharmaceuticals, Pfizer, GlaxoSmithKline, Lung Rx, United Therapeutics, Eli Lilly & Co., Biogen Idec, and mondoBIOTECH, Grant monies (from industry related sources): Dr Badesch has received grants from Actelion, Gilead, Encysive Pharmaceuticals, Pfizer, United Therapeutics, Lung Rx, and Eli Lilly & Co., Grant monies (from sources other than industry): Dr Badesch has received grants from the NIH/NHLBI, Other: Dr Badesch has received honoraria for his service on the REVEAL Steering Committee, which is supported by Actelion

Harrison Farber: Consultant fee, speaker bureau, advisory committee, etc.: Dr Farber serves as a consultant for Actelion, Gilead, and United Therapeutics and is on the speaker's bureau for Actelion and Gilead, Grant monies (from industry related sources): Dr Farber has received a research grant from United Therapeutics , Other: Dr Farber has received honoraria for his service on the REVEAL Steering Committee, which is supported by Actelion

Michael McGoon: Consultant fee, speaker bureau, advisory committee, etc.: Dr McGoon serves as a consultant with Actelion, Gilead, Lung Rx, and Medtronic, Grant monies (from industry related sources): Dr McGoon has received grants from Gilead and Medtronic, Other: Dr McGoon has received honoraria for his service on the REVEAL Steering Committee, which is supported by Actelion

A. Frost: Consultant fee, speaker bureau, advisory committee, etc.: Dr Frost serves as a consultant for Actelion and Gilead and has received honoraria from Actelion, Gilead, and Pfizer, Grant monies (from industry related sources): Dr Frost has received (through Baylor College of Medicine) funds for IRB-approved research from Gilead, Actelion, United Therapeutics, Eli Lilly, Pfizer, Novartis and Bayer, Other: Dr Frost has received honoraria for her service on the REVEAL Steering Committee, which is supported by Actelion

C. Gregory Elliott: Grant monies (from industry related sources): Dr Elliott has received grant support from Actelion, Pfizer, Encysive Pharmaceuticals, and United Therapeutics, Other: Dr Elliott has received honoraria for his service on the REVEAL Steering Committee, which is supported by Actelion

Raymond Benza: Consultant fee, speaker bureau, advisory committee, etc.: Dr Benza has received honoraria from Actelion, Gilead, and United Therapeutics , Grant monies (from industry related sources): Dr Benza has received or is pending receipt of grants from Actelion, Bayer, Novartis, Pfizer, and United Therapeutics, Grant monies (from sources other than industry): Dr Benza has received or is pending receipt of grants from the AHA and the NIH/NHLBI, Other: Dr Benza has received honoraria for his service on the REVEAL Steering Committee, which is supported by Actelion

Abby Poms: Consultant fee, speaker bureau, advisory committee, etc.: Abby Poms serves as a consultant for clinical research studies and advisory boards for Actelion, Gilead, United Therapeutics, GlaxoSmithKline, and GeneraMedix, and has received honoraria for speaker bureau participation for Actelion, Gilead, and United Therapeutics, Grant monies (from industry related sources): Abby Poms has received grants from United Therapeutics and GlaxoSmithKline

Dave Miller: Other: Dave Miller is employed by ICON Late Phase and Outcomes Research, a company that receives research support from Actelion and other pharmaceutical companies

Robyn Barst: Consultant fee, speaker bureau, advisory committee, etc.: Dr Barst serves as a consultant for and has received honoraria from Actelion, Bayer, GlaxoSmithKline, GeneraMedix, Gilead, Eli Lilly & Co., MondoBIOTECH, NIH/NHLBI, Novartis, and Pfizer, Grant monies (from industry related sources): Dr Barst has received grants from Actelion, Gilead, Eli Lilly & Co., Novartis, Pfizer, and United Therapeutics, Grant monies (from sources other than industry): Dr Barst has received grants from the NIH/NHLBI, , Other: Dr Barst has received honoraria for her service on the REVEAL Steering Committee, which is supported by Actelion

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