Long-term therapy with inhaled iloprost in patients with pulmonary hypertension

Respir Med. 2010 May;104(5):731-40. doi: 10.1016/j.rmed.2010.01.008. Epub 2010 Feb 11.

Abstract

Aims: To investigate the long-term safety of inhaled iloprost in patients with pulmonary hypertension (pH), including idiopathic PAH (IPAH group) and other forms of pulmonary hypertension (PHother).

Methods and results: Sixty-three patients (IPAH group, n=40, PHother n=23) were enrolled to receive inhaled iloprost either from baseline or after 3 months in a prospective, open-label 2-year study. Iloprost was inhaled 6-9 times daily with a night pause employing a jet nebulizer delivering an inhaled single dose of 4microg at the mouthpiece. In the case of side effects the single dose was reduced to 2microg. Sixty patients received at least 1 dose of inhaled iloprost. Thirty-six patients completed at least 630 days of therapy (25 IPAH, 11 PHother), 19 patients dropped out prematurely and 8 patients died (3 IPAH, 5 PHother). There were no drug-induced toxicities and only mild to moderate side effects. The most common side effects were coughing and flushing. Two-year survival was estimated at 85% (IPAH group 91%, PHother 78%). A modified analysis was performed to correct for differential drop-out. It included follow-up data from the premature discontinuations and revealed a 2-year survival of 87% [95% CI, 76%-98%] in the IPAH group while the predicted survival was 63%. The iloprost dose increased by 16% over 2 years.

Conclusion: Inhaled iloprost is well tolerated as long-term therapy and no substantial dose increase is required. Although uncontrolled, the data suggest a long-term clinical benefit from continued therapy with inhaled iloprost.

Trial registration: ClinicalTrials.gov NCT00414687.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adult
  • Aged
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Humans
  • Hypertension, Pulmonary / chemically induced
  • Hypertension, Pulmonary / mortality
  • Hypertension, Pulmonary / physiopathology*
  • Iloprost / administration & dosage*
  • Iloprost / adverse effects
  • Male
  • Middle Aged
  • Prospective Studies
  • Time Factors
  • Treatment Outcome
  • Vascular Resistance / drug effects
  • Vascular Resistance / physiology*
  • Vasodilator Agents / administration & dosage*
  • Vasodilator Agents / adverse effects
  • Young Adult

Substances

  • Vasodilator Agents
  • Iloprost

Associated data

  • ClinicalTrials.gov/NCT00414687