GIESSEN, GERMANY—Inhaled iloprost is effective for severe pulmonary hypertension. In a recent placebo-controlled study, patients receiving inhaled iloprost had significant improvement in several clinically important outcomes.[1]

The Aerosolized Iloprost Randomized Study Group is an international team of researchers—supported by Schering—who evaluated the effects of inhaled iloprost in 203 patients with pulmonary hypertension. The primary end point of the study was a 10% increase in the distance walked in six minutes with concomitant improvement in New York Heart Association (NYHA) functional class.

Patients were randomly assigned to receive either 2.5 or 5 µg of inhaled iloprost, six or nine times daily with an overnight break, or placebo. Right heart catheterization was performed in all patients at baseline and at 12 weeks. At baseline, and after four, eight, and 12 weeks of therapy, patients completed a six-minute walk test. Dyspnea, quality of life, and general health were also evaluated (using standardized questionnaires) at these four times.

SUGNIFICANT IMPROVEMENT OVER PLACEBO

More patients in the iloprost group than in the placebo cohort experienced a 10% or greater increase in distance walked in six minutes (38% vs 26%, respectively), but the difference between the two groups did not reach significance. However, the absolute change in distance walked was significantly larger (by 36.4 meters) in the iloprost group.

An improvement in NYHA class was seen in about 25% of the patients given iloprost, compared with 13% of placebo recipients. Because some patients experienced an improvement in functional class but not in walking distance (or vice versa), the combined end point was achieved by only 17% of the iloprost group and 5% of the placebo cohort. Researchers noted, however, that a number of patients in the iloprost group met less strict criteria for clinical improvement, which would justify continued therapy.[1]

After 12 weeks of treatment, hemodynamic values were markedly different in the two groups. In the placebo group, these values had decreased significantly from baseline. In the treatment group, hemodynamic values and gas exchange were mostly unchanged from baseline before the first morning dose of inhaled iloprost was administered; after the first morning dose, these values all improved significantly. At 12 weeks, the treatment and placebo groups had equal acute hemodynamic responses to inhaled iloprost, indicating that tolerance did not develop after three months of daily use.

Clinical deterioration criteria were met in 4.9% of the treatment group and 8.8% of the placebo group. The incidence of adverse effects did not differ between groups.

AN ALTERNATIVE TO IV THERAPY

The mean dose of inhaled iloprost corresponded to 0.37 ng/kg/min, which is considerably lower than an effective intravenous or subcutaneous dose. Using an inhalation method may substantially reduce drug requirements.

In an interview, Timothy Higenbottam, MD, Professor, Section of Respiratory Medicine, Sheffield University Medical School in the United Kingdom, and one of the study’s authors, pointed out that there is no single therapy for pulmonary hypertension, and the only inhaled form of treatment currently available is an investigational use of sildenafil.

Although continuous intravenous therapy may provide better maintenance of hemodynamic improvement, there are risks—relapse after interruption of therapy, complications, and difficult administration—not seen with inhaled therapy. However, Dr. Higenbottam added, “Iloprost is only a step towards sustained therapy. It has too short a duration of effect to be the solution.”

Long-term IV Epoprostenol

CHICAGO—Long-term administration of epoprostenol prolongs survival of patients with primary pulmonary hypertension (PPH), a new study shows. Previous investigations of this agent had focused only on short-term outcomes. Researchers from the Rush Heart Institute in Chicago used the National Institute of Health’s PPH registry to develop a customized database that collected information on 162 consecutive patients who were treated with continuous intravenous (IV) epoprostenol between November 1, 1991, and December 31, 2001.[1] Epoprostenol was administered continuously via a portable infusion pump. During an initial hospitalization, the drug was started at a dosage of 2 ng/kg/min and then gradually increased to the maximum tolerated dosage. The dosage could be adjusted thereafter depending on PPH symptoms and the drug’s side effects. The observed survival was 87.8% at one year, 76.3% at two years, and 62.8% at three years, compared with the predicted survivals (also from the NIH registry) of 58.9%, 46.3%, and 35.4%, respectively. IV epoprostenol also improved functional class at the first follow-up period, and hemodynamics and exercise time at the first and second follow-up periods. (First follow-up took place a mean of 17 months after treatment was initiated; second follow-up took place a mean of 13 months later.) The benefits of epoprostenol therapy were most apparent at the first follow-up period. However, therapy slowed clinical deterioration at all subsequent periods, suggesting a continued benefit. The major drawbacks of chronic epoprostenol therapy were those associated with the use of an indwelling catheter. —Gale Jurasek

Reference 1. McLaughlin VV, Shillington A, Rich S. Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Circulation. 2002;106:1477-1482.

—Gale Jurasek

Reference
1. McLaughlin VV, Shillington A, Rich S. Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Circulation. 2002;106:1477-1482.

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