Therapy For Pulmonary Arterial Hypertension In Adults

Publication Date: January 1, 2019
Last Updated: March 14, 2022

Recommendations

We suggest that the severity of a PAH patient’s disease be evaluated in a systematic and consistent manner, using a combination of WHO functional capacity (FC), exercise capacity, echocardiographic, laboratory and hemodynamic variables in order to inform therapeutic decisions. (U-CBS)
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We suggest that, whenever possible, all PAH patients be evaluated promptly at a center with expertise in the diagnosis of PAH, ideally prior to the initiation of therapy. (U-CBS)
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We suggest collaborative and closely coordinated care of PAH patients involving the expertise of both local physicians and those with expertise in PAH care. (U-CBS)
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Treatment Naive PAH Patients Without Symptoms (WHO FC I) and Patients at Increased Risk for the Development of PAH

For treatment-naive PAH patients with WHO FC I symptoms, we suggest continued monitoring for the development of symptoms that would signal disease progression and warrant the initiation of pharmacotherapy. (U-CBS)
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We suggest that patients at increased risk for the development of PAH be monitored for the development of symptoms of PAH. (U-CBS)
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We suggest also that contributing causes of PH (eg, sleep apnea and systemic hypertension) in patients with PAH be treated aggressively. (U-CBS)
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Symptomatic Patients With PAH

Vasoreactivity Testing and Use of Calcium Channel Blockers (CCBs)

We suggest that patients with PAH, in the absence of contraindications, should undergo acute vasoreactivity testing using a short-acting agent at a center with experience in the performance and interpretation of vasoreactivity testing. (U-CBS)
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We suggest that patients with PAH who, in the absence of right-sided heart failure or contraindications to CCB therapy, demonstrate acute vasoreactivity according to consensus definition, should be considered candidates for a trial of therapy with an oral CCB. (U-CBS)
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We suggest that CCBs should not be used empirically to treat PAH in the absence of demonstrated acute vasoreactivity. (U-CBS)
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PAH-Specific Pharmacotherapies

For treatment naive PAH patients with WHO FC II and III, we suggest initial combination therapy with ambrisentan and tadalafil to improve six-minute walk distance (6MWD). (W-M)
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Patients With WHO FC II Symptoms

For treatment-naive patients with PAH with WHO FC II symptoms who are not candidates for, or who have failed, CCB therapy, we advise that therapy be initiated with a combination of ambrisentan and tadalafil. For patients who are unwilling or unable to tolerate combination therapy, we advise monotherapy with a currently approved ERA, PDE5I inhibitor, or the soluble guanylate cyclase stimulator riociguat as outlined in the 2014 guidelines. More specifically in these patients:
  • We recommend ambrisentan to improve 6MWD.
(S-L)
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  • We suggest bosentan to delay time to clinical worsening.
(U-CBS)
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  • We suggest macitentan to delay the time to clinical worsening.
(U-CBS)
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  • We recommend sildenafil to improve 6MWD.
(S-L)
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  • We suggest tadalafil to improve 6MWD.
(U-CBS)
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  • We suggest riociguat to improve 6MWD, improve WHO FC and delay the time to clinical worsening.
(U-CBS)
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We suggest that parenteral or inhaled prostanoids not be chosen as initial therapy for treatment naive PAH patients with WHO FC II symptoms or as second line agents for PAH patients with WHO FC II symptoms who have not met their treatment goals. (U-CBS)
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Patients With WHO FC III Symptoms

For treatment-naive PAH patients with WHO FC III symptoms who are not candidates for, or who have failed CCB therapy, we advise that therapy be initiated with a combination of ambrisentan and tadalafil. For patients who are unwilling or unable to tolerate combination therapy, we advise monotherapy with a currently approved ERA, a PDE5I, or the soluble guanylate cyclase stimulator riociguat. More specifically in these patients:
  • We recommend the use of bosentan to improve 6MWD.
(S-M)
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  • We suggest the use of bosentan to decrease hospitalizations related to PAH in the short-term.
(W-L)
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  • We recommend the use of ambrisentan to improve 6MWD.
(S-L)
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  • We suggest macitentan to improve WHO FC and delay the time to clinical worsening.
(U-CBS)
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  • We recommend the use of sildenafil to improve 6MWD.
(S-L)
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  • and to improve WHO FC.
(U-CBS)
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  • We suggest the use of tadalafil to improve 6MWD, to improve WHO FC and to delay time to clinical worsening.
(U-CBS)
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  • We suggest riociguat to improve 6MWD (Ungraded Consensus-Based Statement), improve WHO FC, delay the time to clinical worsening.
(U-CBS)
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For treatment naive PAH patients with WHO FC III symptoms who have evidence of rapid progression of their disease, or other markers of a poor clinical prognosis, we advise consideration of initial treatment with a parenteral prostanoid. More specifically in these patients:
  • We suggest continuous IV epoprostenol to improve FC and improve 6MWD.
(U-CBS)
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  • We suggest continuous IV treprostinil to improve 6MWD.
(U-CBS)
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  • We suggest continuous subcutaneous treprostinil to improve 6MWD.
(U-CBS)
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For PAH patients in WHO FC III who have evidence of progression of their disease, and/or markers of poor clinical prognosis despite treatment with one or two classes of oral agents, we advise consideration of the addition of a parenteral or inhaled prostanoid.
More specifically in these patients:
  • We suggest IV epoprostenol to improve WHO FC and improve 6MWD.
(U-CBS)
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  • We suggest IV treprostinil to improve 6MWD.
(U-CBS)
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In patients with PAH who remain symptomatic on stable and appropriate doses of an ERA or a PDE5I, we suggest the addition of inhaled treprostinil to improve 6MWD. (W-L)
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In patients with PAH who remain symptomatic on stable and appropriate doses of an ERA or a PDE5I, we suggest the addition of inhaled iloprost to improve WHO FC and delay the time to clinical worsening. (U-CBS)
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Patients With WHO FC IV Symptoms

For treatment naive PAH patients in WHO FC IV, we advise initiation of therapy with a parenteral prostanoid agent. More specifically in these patients:
  • We suggest continuous IV epoprostenol to improve WHO FC and improve 6MWD.
(U-CBS)
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  • We suggest continuous IV treprostinil to improve 6MWD.
(U-CBS)
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  • We suggest continuous subcutaneous treprostinil to improve 6MWD.
(U-CBS)
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For treatment naive PAH patients in WHO FC IV who are unable or do not desire to manage parenteral prostanoid therapy, we advise treatment with an inhaled prostanoid in combination with an oral PDE5I and an ERA. (U-CBS)
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PAH Patients on Established PAH-Specific Therapy

In patients with PAH initiating therapy with IV epoprostenol, we suggest against the routine simultaneous initiation of bosentan. (U-CBS)
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For WHO FC III or IV PAH patients with unacceptable clinical status despite established PAH- specific monotherapy, we advise addition of a second class of PAH therapy to improve exercise capacity. Such patients are ideally evaluated at centers with expertise in the evaluation and treatment of patients with PAH. More specifically:
  • In patients with PAH who remain symptomatic on stable doses of an ERA or a PDE5I, we suggest the addition of inhaled iloprost to improve 6MWD.
(U-CBS)
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  • In patients with PAH who remain symptomatic on stable doses of an ERA or a PDE5I, we recommend the addition of inhaled treprostinil to improve 6MWD.
(S-L)
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  • In patients with PAH who remain symptomatic on stable doses of established IV epoprostenol, we suggest the addition of sildenafil or up titration of epoprostenol to improve 6MWD.
(U-CBS)
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In patients with PAH who remain symptomatic on stable doses of bosentan, ambrisentan or an inhaled prostanoid, we suggest the addition of the soluble guanylate cyclase stimulator riociguat to improve 6MWD, WHO FC and to delay the time to clinical worsening. (U-CBS)
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In patients with PAH who remain symptomatic on stable doses of a PDE5I or an inhaled prostanoid we suggest macitentan to improve 6MWD, WHO FC
and to delay the time to clinical worsening. (U-CBS)
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For WHO FC III or IV PAH patients with unacceptable or deteriorating clinical status despite established PAH-specific therapy with two classes of PAH pharmacotherapy, we suggest addition of a third class of PAH therapy. (U-CBS)
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Combination Studies of Endothelin Receptor Antagonists and Phosphodiesterase Inhibitors

For stable or symptomatic PAH patients on background therapy with ambrisentan, we suggest the addition of tadalafil to improve 6MWD. (W-L)
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Palliative Care and Supportive Therapies

We suggest incorporating palliative care services in the management of PAH patients. (U-CBS)
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We suggest that patients with PAH participate in supervised exercise activity as part of the integrated care of their disease. (U-CBS)
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Preventive Care

In patients with PAH, we suggest maintaining current immunization against influenza and pneumococcal pneumonia. (U-CBS)
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Specific Patient Situations

Pregnancy
In patients with PAH, we suggest that pregnancy be avoided. (U-CBS)
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When pregnancy does occur in patients with PAH, we suggest care at a pulmonary hypertension center with experience in this area, using a multidisciplinary approach including the pulmonary hypertension, the high-risk obstetrical, and cardiovascular anesthesiology services. (U-CBS)
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Altitude and Air Travel
In patients with PAH, we suggest that exposure to high altitude be avoided, and that supplemental oxygen be used as needed during altitude exposure or air travel to maintain oxygen saturations >91%. (U-CBS)
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Surgery
In patients with PAH, we suggest avoiding nonessential surgery, and when surgery is necessary we suggest care at a pulmonary hypertension center, using a multidisciplinary approach including the pulmonary hypertension team, the surgical service, and cardiovascular anesthesiology with careful monitoring and management of clinical status, oxygenation and hemodynamics postoperatively. (U-CBS)
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Recommendation Grading

Overview

Title

Therapy For Pulmonary Arterial Hypertension In Adults

Authoring Organization

Publication Month/Year

January 1, 2019

Last Updated Month/Year

January 29, 2024

Supplemental Implementation Tools

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Document Objectives

Pulmonary arterial hypertension (PAH) carries a poor prognosis if not promptly diagnosed and appropriately treated. The development and approval of 14 medications over the last several decades have led to a rapidly evolving approach to therapy, and have necessitated periodic updating of evidence-based treatment guidelines. This guideline statement, which now includes a visual algorithm to enhance its clinical utility, represents the fourth iteration of the American College of Chest Physicians Guideline and Expert Panel Report on Pharmacotherapy for PAH.

Target Patient Population

Adult patients with pulmonary arterial hypertension

Inclusion Criteria

Female, Male, Adolescent, Adult, Older adult

Health Care Settings

Ambulatory, Hospital, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Diagnosis, Management, Treatment

Diseases/Conditions (MeSH)

D006976 - Hypertension, Pulmonary, D000081029 - Pulmonary Arterial Hypertension

Keywords

hypertension, pulmonary arterial hypertension

Supplemental Methodology Resources

Data Supplement, Data Supplement

Methodology

Number of Source Documents
52
Literature Search Start Date
January 1, 2012
Literature Search End Date
July 1, 2016