Pulmonary arterial hypertension
ICD-10 I27.0 · ICD-11 BB01.0

What to Do for Non-Vasoreactive PAH at High Risk When Triple-Combination Therapy Fails to Achieve Low-Risk Status

This protocol targets patients with non-vasoreactive idiopathic, heritable, or drug-associated PAH — or PAH associated with connective tissue disease — who have a negative acute pulmonary vasoreactivity test, no significant cardiopulmonary comorbidities, and remain at high risk of death despite prior escalation.

Clinical scenario

Patients in this group carry a high risk of death and have not responded adequately to optimized medical therapy. The absence of cardiopulmonary comorbidities and the confirmed non-vasoreactive phenotype (negative acute vasoreactivity test) define this sub-population.

Previous line — failure condition

These patients were treated with initial triple-combination therapy: a phosphodiesterase 5 inhibitor, an endothelin receptor antagonist, and an intravenous or subcutaneous prostacyclin analogue. The escalation trigger is failure to achieve and maintain a low-risk profile on that optimized regimen — as assessed by WHO functional class, six-minute walk distance, and BNP/NT-proBNP.

Next step — treatment approach

When a patient remains at high risk despite maximally optimized medical therapy, a transplantation evaluation pathway becomes indicated. The full protocol specifies which patients qualify for referral and the criteria used to determine candidacy and listing priority.

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References

DOI: 10.1093/eurheartj/ehac237

In patients with IPAH/HPAH/DPAH who present at high risk of death, initial combination therapy with a PDE5i, an ERA, and i.v./s.c. prostacyclin analogues should be considered.

In patients presenting at high risk, initial triple-combination therapy including an i.v./s.c. prostacyclin analogue should be considered.

It is recommended that potentially eligible candidates are referred for LTx evaluation when they have an inadequate response to oral combination therapy, indicated by an intermediate–high or high risk or by a REVEAL risk score >7.

It is recommended to list patients for LTx who present with a high risk of death or with a REVEAL risk score ≥10 despite receiving optimized medical therapy including s.c. or i.v. prostacyclin analogues.

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