Vasoreactive Idiopathic, Heritable, or Drug-Associated PAH When Calcium Channel Blockers Did Not Achieve Target Response

This protocol applies to patients with idiopathic, heritable, or drug-associated pulmonary arterial hypertension who had a positive acute pulmonary vasoreactivity test — a drop of ≥10 mmHg in mean pulmonary arterial pressure to ≤40 mmHg with increased or unchanged cardiac output — and were subsequently treated with high-dose calcium channel blockers, but did not achieve the defined targets of satisfactory chronic response.

Clinical Scenario

Patients with IPAH, HPAH, or DPAH who respond favourably to acute vasoreactivity testing may initially be treated with high-dose calcium channel blockers. A durable, satisfactory response requires both functional and haemodynamic normalisation confirmed by right heart catheterisation at 3–4 months. Not all vasoreactive patients sustain this response long-term.

Previous Therapy: Targets Not Met

The prior protocol involved high doses of calcium channel blockers — amlodipine, diltiazem, felodipine, or nifedipine — titrated to individually optimised doses. A satisfactory chronic response required all of the following at reassessment:

WHO functional class I or II
mPAP below 30 mmHg and PVR below 4 Wood units
BNP below 50 ng/L or NT-proBNP below 300 ng/L

Failure to achieve one or more of these targets — confirmed by right heart catheterisation — indicates that this next-step protocol is warranted.

Next-Step Approach

The structured protocol initiates targeted PAH-specific therapy, including an endothelin receptor antagonist, with further agents and specific considerations for patients who had a positive vasoreactivity test but an insufficient long-term response. The complete regimen, combination strategy, and sequencing are available in the full protocol.

Instant Access to Structured Evidence-Based Regimens

References

DOI: 10.1093/eurheartj/ehac237

Patients with PAH who respond favourably to acute vasoreactivity testing may respond favourably to treatment with CCBs.
High doses of CCBs are recommended in patients with IPAH, HPAH, or DPAH who are responders to acute vasoreactivity testing.
Initiating PAH therapy is recommended in patients who remain in WHO-FC III or IV or those without marked haemodynamic improvement after high doses of CCBs.
In patients with a positive vasoreactivity test but insufficient long-term response to CCBs who require additional PAH therapy, continuation of CCB therapy should be considered.

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