Pulmonary Disorders II

3 Wood units and an mPAP greater than 25 mm Hg. Although the definition of PAH now includes

those with an mPAP of 20 to 25 mm Hg and a PVR of 2 to 3 Wood units, these populations have not

been included in clinical trials to date assessing PAH pharmacotherapies and remain an area for future

research.

Drug therapy should be evaluated on the basis of the patient-specific factors below (Eur Respir J.

2024;64(4):2401324; Eur Heart J 2022;43:3618-731):

Mortality risk assessment using the 3-strata model (low, intermediate, high), as shown in

(low risk), 2 points (Intermediate risk), or 3 points (high risk). The total score is added

and divided by the number of variables assessed. Patients are classified as having low-,

intermediate-, or high-risk disease if their scores are less than 1.5, 1.5 to 2.49, or more than

2.49, respectively (Eur Respir J. 2024;64(4):2401323).

ii.

Presence of cardiopulmonary comorbidities that are associated with increased risk of LV

diastolic dysfunction (obesity, hypertension, diabetes, coronary heart disease)

iii.

Ability and willingness to manage parenteral prostacyclins

iv.

Access to resources

Initial therapy in patients without cardiopulmonary comorbidities

Low- or intermediate-risk strata (Table 4): combination therapy with an endothelin receptor

antagonist (ERA) and a phosphodiesterase type 5 inhibitor (PDE5i)

Engl J Med. 2015;373:834-844; Am Coll Cardiol. 2024;83(4):473-484).

ii.

High-risk strata: combination therapy with ERA, PDE5i, and parenteral prostacyclin

Initial and subsequent therapy in patients with cardiopulmonary comorbidities: because these

patients are under-represented in clinical studies, no evidence-based recommendations can be

provided. Although these patients are often treated similarly in practice, they have more treatment-

related adverse effects or tolerability issues with combination therapy.

All risk strata: oral monotherapy with PDE5i or ERA

ii.

Follow-up therapeutic changes should be based on patient-specific characteristics

Subsequent therapeutic options are based on the four strata risk assessment (Table 5). All 3 variables are

recommended to be included in each follow-up assessment for better accuracy at predicting mortality.

If only 2 variables are available, it is preferred to include 1 biomarker (BNP or NT-proBNP) and 1

functional marker (either WHO-FC or 6MWD). To determine risk category, each variable available is

categorized a point value as 1 point (low risk), 2 points (intermediate-low risk), 3 points (Intermediate-

high risk), or 4 points (high risk). The total score is added and divided by the number of variables

assessed. Patients are classified as having low-, intermediate-low, intermediate-high, or high-risk

disease if their scores are less than 1.5, 1.5 to 2.49, 2.5 to 3.49, or more than 3.49, respectively (Eur Respir

592).

Low-risk strata: Continue current therapy

Intermediate/Low-risk strata

Add an oral or inhaled prostacyclin receptor agonist (PRA)—or—

ii.

Switch from PDE5i to soluble guanylate cyclase stimulator (sGC)—or—

iii.

Add an activin-signaling inhibitor (N Engl J Med. 2023;388(16):1478-1490).