Treatment of Idiopathic, Heritable, or Drug-Associated PAH with a Positive Acute Vasoreactivity Test
In patients with idiopathic (IPAH), heritable (HPAH), or drug-associated (DPAH) pulmonary arterial hypertension, a positive acute vasoreactivity test — defined as a reduction in mean pulmonary arterial pressure (mPAP) of ≥10 mmHg, reaching ≤40 mmHg, with maintained or increased cardiac output — identifies a distinct sub-population with a specific evidence-based treatment pathway.
Acute vasoreactivity testing is a key step in stratifying patients with IPAH, HPAH, or DPAH. Patients who respond favourably to this test may respond favourably to a targeted pharmacological approach that is not indicated for non-responders. Identifying this group is therefore a prerequisite for selecting the appropriate first-line treatment.
Vasoreactivity responders are candidates for treatment with high doses of calcium channel blockers, titrated progressively to the optimised individual dose — the specific agents, titration schedule, and full regimen are detailed in the complete protocol.
A satisfactory chronic response requires reassessment at 3–4 months (including right heart catheterisation) confirming WHO Functional Class I or II with marked haemodynamic improvement: mPAP below 30 mmHg, pulmonary vascular resistance below 4 Wood units, and BNP below 50 ng/L or NT-proBNP below 300 ng/L.
- Patients with PAH who respond favourably to acute vasoreactivity testing (Figure 8) 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.
- The CCBs that have predominantly been used in PAH are nifedipine, diltiazem, and amlodipine.
- The daily doses that have shown efficacy in PAH are relatively high and they must be reached progressively (Table 19).
- Close follow-up with complete reassessment after 3–4 months of therapy (including RHC) is recommended in patients with IPAH, HPAH, or DPAH treated with high doses of CCBs.
- Continuing high doses of CCBs is recommended in patients with IPAH, HPAH, or DPAH in WHO-FC I or II with marked haemodynamic improvement (mPAP <30 mmHg and PVR <4 WU).
- WHO-FC I/II, BNP <50 ng/L or NT-proBNP <300 ng/L, normal or near-normal resting haemodynamics.