This is the current release of the guideline.

Note from National Guideline Clearinghouse (NGC) and American College of Chest Physicians (ACCP): In June 2007, the ACCP released an update to their guidelines on medical therapy for pulmonary arterial hypertension, taking into consideration studies published prior to September 1, 2006. Recommendations that have been changed since the original 2004 guideline are displayed below in italics.

Rating schemes for level of evidence, strength of recommendation, and net benefit follow the major recommendations.

1. Patients with idiopathic pulmonary arterial hypertension (IPAH) should undergo acute vasoreactivity testing using a short-acting agent such as intravenous (IV) epoprostenol, adenosine, or inhaled nitric oxide (NO). Level of evidence: fair; benefit: substantial; grade of recommendation: A.
2. Patients with pulmonary arterial hypertension (PAH) associated with underlying processes, such as scleroderma or congenital heart disease, should undergo acute vasoreactivity testing. Level of evidence: expert opinion; benefit: small/weak; grade of recommendation: E/C.
3. Patients with PAH should undergo vasoreactivity testing by a physician experienced in the management of pulmonary vascular disease. Level of evidence: expert opinion; benefit: substantial; grade of recommendation: E/A.
4. Patients with IPAH, in the absence of right-heart failure, demonstrating a favorable acute response to vasodilator (defined as a fall in mean pulmonary arterial pressure [mPAP] of at least 10 mm Hg to <40 mm Hg, with an increased or unchanged cardiac output [CO]), should be considered candidates for a trial of therapy with an oral calcium-channel antagonist. Level of evidence: low; benefit: substantial; grade of recommendation: B.
5. Patients with PAH associated with underlying processes such as scleroderma or congenital heart disease, in the absence of right-heart failure, demonstrating a favorable acute response to vasodilator (defined as a fall in mean pulmonary arterial pressure [mPAP] of at least 10 mm Hg to <40 mm Hg, with an increased or unchanged CO), should be considered candidates for a trial of therapy with an oral calcium-channel antagonist. Level of evidence: expert opinion; benefit: intermediate; grade of recommendation: E/B.
6. In patients with PAH, calcium-channel blockers (CCBs) should not be used empirically to treat pulmonary hypertension (PH) in the absence of demonstrated acute vasoreactivity. Level of evidence: expert opinion; benefit: substantial; grade of recommendation: E/A.
7. Patients with IPAH should receive anticoagulation with warfarin. Level of evidence: fair; benefit: intermediate; grade of recommendation: B.
8. In patients with PAH occurring in association with other underlying processes, such as scleroderma or congenital heart disease, anticoagulation should be considered. Level of evidence: expert opinion; benefit: small/weak; recommendation: E/C.
9. In patients with PAH, supplemental oxygen should be used as necessary to maintain oxygen saturations at >90% at all times. Level of evidence: expert opinion; benefit: substantial; recommendation: E/A.
10. PAH patients in functional class II who are not candidates for, or who have failed, CCB therapy, may benefit from treatment with:
    1. Sildenafil. Level of evidence: good; benefit: substantial; grade of recommendation: A
    2. Subcutaneous treprostinil. Level of evidence: low; benefit: small/weak; grade of recommendation: C. Although treprostinil is U.S. Food and Drug Administration (FDA) approved for use in patients in functional class II, it would seldom be recommended in such patients due to the complexity of administration, side effects, and cost.
    3. IV treprostinil. Level of evidence: low; benefit: small/weak; grade of recommendation: C. Although treprostinil is U.S. Food and Drug Administration (FDA) approved for use in patients in functional class II, it would seldom be recommended in such patients due to the complexity of administration, side effects, and cost.
    4. Data pertaining to the treatment of functional class II patients remain limited, and enrollment in clinical trials is encouraged.

11. PAH patients in functional class III who are not candidates for, or who have failed, CCB therapy are candidates for long-term therapy with:
    1. Endothelin-receptor antagonists (bosentan), or sildenafil, in no order of preference. Level of evidence: good; benefit: substantial; grade of recommendation: A.
    2. IV epoprostenol. Level of evidence: good; benefit: substantial; grade of recommendation: A.
    3. Inhaled iloprost. Level of evidence: good; benefit: intermediate; grade of recommendation: A.
    4. Subcutaneous treprostinil. Level of evidence: fair; benefit: intermediate; grade of recommendation: B.
    5. IV treprostinil. Level of evidence: low; benefit: intermediate; grade of recommendation: C.

12. PAH patients in functional class IV who are not candidates for, or who have failed, CCB therapy are candidates for long-term therapy with IV epoprostenol (treatment of choice). Level of evidence: good; benefit: substantial; grade of recommendation: A.
13. Other treatments available for the treatment of functional class IV PAH include, in no hierarchical order:
    1. Endothelin-receptor antagonists (bosentan). Level of evidence: fair; benefit: intermediate; grade of recommendation: B.
    2. Inhaled iloprost. Level of evidence: fair; benefit: intermediate; grade of recommendation: B.
    3. Subcutaneous treprostinil. Level of evidence: fair; benefit: intermediate; grade of recommendation: B.
    4. Sildenafil. Level of evidence: low; benefit: Intermediate; grade of recommendation: C.
    5. IV treprostinil. Level of evidence: low; benefit: intermediate; grade of recommendation: C.

14. 2004 recommendation has been deleted.
15. 2004 recommendation has been deleted.
16. Children with PAH:
    1. With right-heart failure or with a hypercoagulable state should receive anticoagulation with warfarin. Level of evidence: expert opinion; net benefit: intermediate; strength of recommendation: E/B.
    2. Without right-heart failure or a hypercoagulable state may receive anticoagulation with warfarin; for children <5 years of age, lower target international normalized ratios (INRs) are recommended. Level of evidence: expert opinion; net benefit: small/weak; strength of recommendation: E/C.

17. In patients with PAH, pregnancy should be avoided, or termination recommended. Level of evidence: good; benefit: substantial; grade of recommendation: A.

Definitions:

Quality of the Evidence

Good = evidence based on good randomized controlled trials or meta-analyses

Fair = evidence based on other controlled trials or randomized controlled trials with minor flaws

Low = evidence based on nonrandomized, case-control, or other observational studies

Expert opinion = evidence based on the consensus of the carefully selected panel of experts in the topic field. There are no studies that meet the criteria for inclusion in the literature review.

Strength of Recommendations

A = strong recommendation
B = moderate recommendation
C = weak recommendation
D = negative recommendation
I = no recommendation possible (inconclusive)
E/A = strong recommendation based on expert opinion only
E/B = moderate recommendation based on expert opinion only
E/C = weak recommendation based on expert opinion only
E/D = negative recommendation based on expert opinion only

Net Benefit

Substantial
Intermediate
Small/weak
None
Conflicting
Negative

Relationship of Strength of the Recommendations Scale to Quality of Evidence and Net Benefits

An updated clinical algorithm is provided in the addendum to the original guideline document for treatment of pulmonary arterial hypertension.

The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations").

Not applicable: The guideline was not adapted from another source.

2004 Jul (addendum released 2007 Jun)

American College of Chest Physicians - Medical Specialty Society

Funding for both the evidence reviews and guideline development was provided through an unrestricted educational grant from GlaxoSmithKline, Texas Biotechnology Corporation, and Actelion Pharmaceuticals US. Representatives from these companies were not granted right of review, nor were they allowed participation in any portion of the guideline development.

American College of Chest Physicians (ACCP) Expert Panel on Pulmonary Artery Hypertension

2004 Guideline

Primary Authors: David B. Badesch, MD, FCCP, University of Colorado Health Sciences Center, Denver, CO; Steve H. Abman, MD, Children´s Hospital, Denver, CO; Gregory S. Ahearn, MD, Duke University Medical Center, Durham, NC; Robyn J. Barst, MD, Columbia Presbyterian Medical Center, New York, NY; Douglas C. McCrory, MD, MHSc, Duke University Medical Center, Durham, NC; Gerald Simonneau, MD, Hospital Antoine Beclere, Clamart, France; Vallerie V. McLaughlin, MD, FCCP, Rush Presbyterian St. Lukes Hospital, Chicago, IL

2007 Addendum

Primary Authors: David B. Badesch, MD, FCCP; Steve H. Abman, MD; Gerald Simonneau, MD; Lewis J. Rubin, MD, FCCP; Vallerie V. McLaughlin, MD, FCCP

The following participants have disclosed information regarding potential or real conflicts of interest and commitment:

2004 Guideline

Steven H. Abman, MD: scientific advisory board for INO Therapeutics; consultant for Pfizer.

Charles W. Atwood, Jr., MD, FCCP: research support from Respironics, Inc.

David B. Badesch, MD, FCCP: consultant or Speaker's Bureau for Glaxo Wellcome/GlaxoSmithKline, Actelion, InterMune, Encysive, Myogen, Astra-Merck, Astra-Zeneca, Exhale Therapeutics/CoTherix, Forrest Labs, INO Therapeutics, Berlex; research support from Glaxo Wellcome/GlaxoSmithKline, United Therapeutics, Boehringer Ingelheim, Actelion, Encysive, ICOS/Texas Biotechnologies/Encysive, Myogen, INO Therapeutics, Scleroderma Foundation, National Institutes of Health, National Heart, Lung, and Blood Institute, United Therapeutics, Pfizer, American Lung Association.

Robyn J. Barst, MD: consultant and research support from Actelion, Encysive, Exhale Therapeutics, INO, Myogen, United Therapeutics, Pfizer GlaxoSmithKline; unrestricted education grants from GlaxoSmithKline, Encysive, Actelion.

Richard N. Channick, MD, FCCP: research support from Actelion, Pfizer, Myogen, United Therapeutics; consultant and Speaker's Bureau for Actelion.

Ramona L. Doyle, MD, FCCP: Speaker's Bureau for Actelion; clinical research for Actelion, Myogen, United Therapeutics.

David D. Gutterman, MD, FCCP: stock options with Johnson & Johnson; relative who is a Vice-President at GlaxoSmithKline.

James E. Loyd, MD, FCCP: relationships with GlaxoSmithKline, United Therapeutics, Actelion, ICOS/Texas Biotechnology, Westat, PRA International, Pfizer, Exhale Therapeutics.

Michael D. McGoon, MD: past research support from Glaxo Wellcome, United Therapeutics, Actelion; research support from Texas Biotech/Encysive, Myogen, Pfizer, Medtronic.

Vallerie V. McLaughlin, MD, FCCP: consultant for Actelion, United Therapeutics, Exhale Therapeutics; Speaker's Bureau for Actelion; research funding from Actelion, United Therapeutics, Pfizer, Encysive/Texas Biotechnologies, Glaxo Wellcome, Exhale Therapeutics, Myogen.

Stuart Rich, MD: research funding from Actelion, Pfizer, United Therapeutics, Encysive, Myogen; consultant for Actelion, Pfizer, United Therapeutics, GlaxoSmithKline.

Lewis J. Rubin, MD, FCCP: consultant for Actelion, Myogen, Schering, Exhale Therapeutics, United Therapeutics, Pfizer, Celgene; investigator for Actelion, Myogen, Exhale, Pfizer, Celgene; no stock holdings or other ownerships or positions.

Gerald Simonneau, MD: consultant and investigator for Glaxo Wellcome, Pfizer, Actelion, Schering, Myogen, United Therapeutics.

Virginia D. Steen, MD: relationships with Arthritis Foundation, Scleroderma Foundation, Actelion.

Fredrick M. Wigley, MD: research funding from Biogen, Pfizer, Actelion; consultant to Genzyme.

2007 Addendum

Dr. Badesch has received grant monies from the National Institutes of Health. He has received grant monies from GlaxoSmithKline, United Therapeutics/LungRx, Actelion, Lilly/ICOS, Encysive, Pfizer, Myogen/Gilead, and CoTherix. He has received consultant fees from GlaxoSmithKline, Actelion, Myogen/Gilead, CoTherix, Pfizer, United Therapeutics, Mondo-Biotech, Biogen IDEC, PR Pharmaceuticals, Forrests Labs, Scios, Amgen, Biovale Pharmaceuticals/Clarus Health, and Johnson & Johnson. He has served on the speaker's bureau for GlaxoSmithKline, Actelion, Myogen/Gilead, Encysive, CoTherix, Pfizer, United Therapeutics, Mondo-Biotech, and Biogen IDEC. He has served on the board of directors for the Pulmonary Hypertension Association and the American Thoracic Society.

Dr. Abman has served as a scientific advisor for INO Therapeutics.

Dr. Simonneau has received grant monies from, served on the speaker's bureau for, and served on the advisory committees for Actelion, Pfizer, Schering, United Therapeutics, and GlaxoSmithKline.

Dr. Rubin has received university grant monies from the National Heart, Lung, and Blood Institute. He has received grant monies from Actelion, Pfizer, United Therapeutics, Mondo-Biotech, MD Primer, and Gilead. He is a shareholder in LungRx. He has received consultant fees from the National Heart, Lung, and Blood Institute; Actelion; Pfizer; United Therapeutics; ProQuest; Bayer Schering; and Mondo-Biotech. He is on the advisory committees for Actelion, Pfizer, LungRx, MD Primer, and Encysive.

Dr. McLaughlin has received grant monies from Actelion, Encysive, LungRx, Pfizer, and United Technologies. She has served on the speaker's bureau and advisory committees for Actelion, Gilead, and Pfizer.

This is the current release of the guideline.

None available

This NGC summary was completed by ECRI on August 27, 2004. This summary was updated by ECRI on July 15, 2005 following the FDA advisory on Cialis, Levitra, and Viagra. This summary was updated by ECRI on March 8, 2006 following the FDA advisory on Tracleer (bosentan). This summary was updated by ECRI on March 6, 2007 following the FDA advisory on Coumadin (warfarin sodium). This summary was updated by ECRI Institute on August 8, 2007 following the release of the addendum. This summary was updated by ECRI Institute on September 7, 2007 following the revised U.S. Food and Drug Administration (FDA) advisory on Coumadin (warfarin). This summary was updated by ECRI Institute on November 6, 2007, following the updated U.S. Food and Drug Administration advisory on Viagra, Cialis, Levitra, and Revatio.

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.