Risk Stratification and Medical Therapy of Pulmonary Arterial Hypertension

Publication Date: December 1, 2018
Last Updated: March 14, 2022

Recommendations

Based on global experience collected in the RCTs on PAH patients, the following comments can be proposed:

  • In treatment-naive PAH patients, initial monotherapy is able to improve exercise capacity, haemodynamics and outcome compared with untreated patients.

  • In treatment-naive and newly diagnosed (incident) PAH patients, initial combination therapy is able to improve symptoms, exercise capacity and outcome compared with initial monotherapy.

  • In already treated (prevalent) PAH patients, sequential combination therapy is able to improve exercise capacity, haemodynamics and outcome compared with patients continuing with their background therapy.


Treatment

Initial approach

After confirmation of the diagnosis of the treatment-naive PAH patient in an expert centre, the suggested initial approach is the adoption of general measures and the initiation of supportive therapy (2015 ESC/ERS PH guidelines Tables 16 and 17).
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Acute vasoreactivity testing should be performed to predict response to calcium channel blocker (CCBs) only in patients with IPAH, HPAH, and PAH associated with drugs and toxin use. Vasoreactive patients should be treated with high doses (progressively titrated) of CCBs; adequate response should be confirmed after 3–6 months of treatment (2015 ESC/ERS PH guidelines Table 18). Adequate treatment response to high doses of CCBs is considered WHO FC I/II with sustained haemodynamic improvement (same or better than achieved in the acute test) after at least 1 year on CCBs only. Vasoreactive patients without an adequate treatment response to high doses of CCBs should be treated with approved PAH medications according to the non-vasoreactive patients’ treatment strategy.
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Non-responders to acute vasoreactivity testing who are at low or intermediate risk should be treated with initial oral combination therapy with an ERA and a PDE5i (2015 ESC/ERS PH guidelines Table 20).
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Some specific PAH subsets in which the efficacy/safety ratio of initial combination therapy is not established should be treated with initial monotherapy.
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If initial monotherapy is chosen, as head-to-head comparisons among different compounds are not available, no evidence-based first-line monotherapy can be proposed. The choice of drug may depend on a variety of factors, including approval status, labelling, route of administration, side-effect profile, potential interaction with background therapies, patient preferences, comorbidities, physician experience and cost.
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In non-vasoreactive and treatment-naive patients at high risk, initial combination therapy including i.v. PCAs is recommended (2015 ESC/ERS PH guidelines Table 20). Intravenous epoprostenol receives the strongest recommendation as it has reduced the 3-month rate of mortality in high-risk PAH patients also as monotherapy (2015 ESC/ERS PH guidelines Table 19). Alternative types of initial combination therapy may be considered (2015 ESC/ERS PH guidelines Table 20). Referral for lung transplantation should also be considered.
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Follow-up therapy

When the initial treatment approach results in a low-risk status within 3–6 months, the therapy should be continued and structured follow-up established (2015 ESC/ERS PH guidelines Table 14).
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When the initial treatment approach results in an intermediate-risk status, escalation to triple combination therapy is recommended according to the 2015 ESC/ERS PH guidelines Table 21 or to double combination in case monotherapy has been chosen. The combinations of macitentan and sildenafil, riociguat and bosentan, and selexipag and ERA and/or PDE5i have the highest recommendation and evidence. PCAs should also be considered. The combination of riociguat and PDE5i is contraindicated. Referral for lung transplantation should also be considered.
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When the initial treatment approach results in a high-risk status, maximal medical therapy including i.v. PCAs is recommended (2015 ESC/ERS PH guidelines Table 20). Referral for lung transplantation should also be considered.
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When the second treatment step results in the low-risk status within 3–6 months, the therapy should be continued and structured follow-up continued (2015 ESC/ERS PH guidelines Table 14). Referral for lung transplantation should also be considered according to local rules for organ allocation and average waiting time in the list.

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When the second treatment step results in an intermediate- or high-risk status, escalation to maximal medical therapy is recommended according to the 2015 ESC/ERS PH guidelines Table 21. Maximal medical therapy is considered to be triple combination therapy including a s.c. or an i.v. PCA (i.v. preferred in high-risk status). For patients on intermediate-risk status on double combination therapy with an ERA and a PDE5i or riociguat, the addition of selexipag should be considered. For patients on triple combination therapy including selexipag who remain in the intermediate-risk group or progress to high risk, the substitution with s.c. or i.v. PCAs should be considered. Referral for lung transplantation should also be considered.
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Patients on follow-up with low-risk status who deteriorate to the intermediate- or high-risk group should be treated with double, triple or maximal combination therapy depending on the initial background treatment.
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We recommend consideration of lung transplantation in all patients on maximal triple combination therapy, with priority for those in intermediate- and high-risk groups, in accordance with local rules for organ allocation and average waiting time in the list (2015 ESC/ERS PH guidelines Table 22).
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Balloon atrial septostomy should be regarded as a palliative or bridging procedure in patients deteriorating despite maximal medical therapy.
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Recommendation Grading

Overview

Title

Risk Stratification and Medical Therapy of Pulmonary Arterial Hypertension

Authoring Organization

Publication Month/Year

December 1, 2018

Last Updated Month/Year

January 29, 2024

Supplemental Implementation Tools

Document Type

Other

External Publication Status

Published

Country of Publication

European

Inclusion Criteria

Adolescent, Adult, Older adult

Health Care Settings

Ambulatory, Emergency care, Hospital, Medical transportation, Operating and recovery room

Intended Users

Respiratory therapist, physician, paramedic emt, nurse, athletics coaching, nurse practitioner, physician assistant

Scope

Assessment and screening, Diagnosis, Prevention, Management, Treatment

Diseases/Conditions (MeSH)

D000081029 - Pulmonary Arterial Hypertension

Keywords

lung transplant, Endothelial function, prostacyclin, nitric oxide, endothelin, monotheraphy