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Original Research: PULMONARY VASCULAR DISEASE |

Does the Outcome Justify an Oral-First Treatment Strategy for Management of Pulmonary Arterial Hypertension?Pulmonary Arterial Hypertension Treatment

William K. Cornwell, MD; Vallerie V. McLaughlin, MD, FCCP; Sangeetha M. Krishnan, MS; Melvyn Rubenfire, MD
Author and Funding Information

From the Department of Internal Medicine (Dr Cornwell), and the Division of Cardiovascular Medicine (Drs McLaughlin and Rubenfire and Ms Krishnan), University of Michigan Medical School, Ann Arbor, MI.

Correspondence to: Melvyn Rubenfire, MD, 24 Frank Lloyd Wright Dr, Lobby A, Ste 3700, Ann Arbor, MI 48106-0363; e-mail: mrubenfi@med.umich.edu


Funding/Support: The authors have reported to CHEST that no funding was received for this study.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2011 American College of Chest Physicians


Chest. 2011;140(3):697-705. doi:10.1378/chest.10-3019
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Background:  Guidelines for the treatment of World Health Organization (WHO) functional class (FC) III pulmonary arterial hypertension (PAH) provide for oral (PO) therapy or parenteral prostacyclins at the discretion of expert physicians. The objective of this study was to assess the appropriateness of PO-first treatment in patients with WHO FC III PAH.

Methods:  This study was a retrospective analysis of 79 treatment-naive adult patients with idiopathic, familial, or anorexigen-associated PAH, referred to a single pulmonary hypertension center. Forty-eight received either PO therapy with an endothelin receptor antagonist, calcium channel blocker, or phosphodiesterase inhibitor (PO group) and 31 an IV or subcutaneous (SC) prostacyclin (IV/SC group).

Results:  Patients in the IV/SC group had a significantly worse baseline hemodynamic profile; however, on univariate analysis, there was no association between hemodynamics and mortality. Initial treatment with PO vs IV/SC therapy was associated with a lower overall mortality (20.8% vs 45.2%, P = .02) and a lower 5-year mortality (14.6% vs 32.3%, P = .062). Based on the National Institutes of Health equation, actual survival for patients who received PO therapy was greater than predicted at 5 years. Finally, there were similar improvements between groups in 6-min walk distance (P = .38) at 6 to 12 months after initiation of treatment.

Conclusions:  For WHO FC III PAH that is idiopathic, familial, or anorexigen associated, the clinical decision for treatment with a PO-first strategy is associated with a high survival rate when patients are appropriately risk stratified prior to initiation of therapy. The more potent prostacyclins can be reserved for high-risk patients, those with evidence of disease progression, or those with treatment failure.

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