Long-term Inhaled Nitric Oxide Plus Phosphodiesterase 5 Inhibitors for Severe Pulmonary Hypertension

Background

Inhaled nitric oxide (iNO) is a potent pulmonary vasodilator, but therapeutic experience in patients with severe pulmonary hypertension is scarce.

Methods

Eleven patients with severe pulmonary hypertension, 6 due to pulmonary arterial hypertension and 4 due to chronic thromboembolic disease, were selected for iNO therapy. A phosphodiesterase type 5 inhibitor (PDE5i) was added in cases of clinical worsening. In this study we evaluate the clinical effectiveness and safety of long-term treatment with iNO either alone or combined with a PDE5i.

Results

After 1 month of iNO administration, improvements were observed in World Health Organization functional class, Borg scale (p = 0.003), brain natriuretic peptide levels (p = 0.002) and 6-minute walk test (p = 0.003). After 6 months of treatment, 7 patients had clinical deterioration that was reversed upon adding a PDE5i. One of these patients died in Month 8 and another underwent pulmonary transplantation in Month 9. The clinical condition of the remaining 9 patients was unchanged after 1 year. A second right catheterization showed improvement in mean pulmonary arterial pressure (66 ± 15 mm Hg to 56 ± 18 mm Hg; p = 0.01), pulmonary vascular resistance (1,234 ± 380 dyn/s/cm⁵ to 911 ± 410 dyn/s/cm⁵; p = 0.008) and cardiac index (2.0 ± 0.4 liters/min/m² to 2.5 ± 0.4 liters/min/m²; p = 0.04). There was no significant increase in methemoglobin, no worsening of pulmonary function and no sudden withdrawal syndrome.

Conclusions

We suggest that iNO therapy alone or in combination with a PDE5i could be a therapeutic alternative for severe pulmonary hypertension.