Inhaled Iloprost for Severe Pulmonary Hypertension - Inhaled Iloprost for Severe Pulmonary Hypertension
The goal of this study was to asses the safety and efficacy of aerosolized iloprost, a stable analogue of prostacyclin, on exercise tolerance and the hemodynamic profile in patients with severe pulmonary hypertension (PH).
NYHA Class: III or IV
A randomized placebo controlled trial of aerosolized iloprost in NYHA class III or IV pulmonary hypertension attributable to either primary pulmonary hypertension, scleroderma related disorders, or thromboembolic pulmonary hypertension. Patients were refractory to standard treatment, had no previous use of prostanoids, and achieved between 50 and 500 meters on a 6-min walk test. Patients were randomly assigned iloprost (101 pts) or placebo (102 pts) after stratifation by NHYA class and type of PH (primary or non-primary). The dose was increased from 2.5 micrograms to 5 micrograms if tolerable, and administered 6 to 9 times daily with an overnight break.
There was no between group difference in average age (52 years), weight (72 kilograms), gender (67% female), calcium channel blocker therapy (50%), NYHA class (40% class IV), the Dyspnea Index, or average 6-min walk distance of about 325 meters), mean pulmonary artery pressure of 53 mm Hg, right atrial pressure of 9 mm Hg, CO of 3.8 Liters / min, pulmonary vascular resistance of 12.9 Wood units, arterial 02 saturation (92%) and mixed venous 02 satruation (60%). 91% of patients received 5 micrograms per inhalation with an average dose of 30 micrograms per day. A combined clinical endpoint of a 10% improvement in the 6-meter walk and better NYHA class was met by 16.8% of the iloprost group compared to 4.9% of placebo, p=0.007, but the percentage who increased the distance by at least 10% did not differ. The 6-meter walk distance increased by 36.4 meters and 58.8 meters in those with primary pulmonary hypertension. 4% of the iloprost and 13.7% of placebo did not complete the study (p = 0.024), the most common reason being clinical deterioration. Hemodynamic parameters deteriorated in the placebo group after 12 weeks, and remained largely unchanged among iloprost patients. At 12 weeks the acute hemodynamic response to iloprost was equivalent in the placebo and iloprost groups. Compared to placebo, iloprost was associated with a significant improvement in NYHA, dyspnea, and quality of life. Iloprost was associated with flushing as the other prostanoids, but there were no serious side effects.
Among patients with severe pulmonary hypertension, inhaled iloprost is associated with an improvement in the combined endpoint of 6 minute walk destance and the NYHA classification. The effects of iloprost in these patients with relatively severe and symptomatic pulmonary hypertension were modest but encouraging. Long term intravenous epoprostanol is considerably more potent and is associated with vascular remodeling. The ideal role for inhaled iloprost may be patients with more modest pulmonary hypertension, or in combination therapy with the endothelin antagonists. Inhaled iloprost may be particularly effective compared to other therapies in pulmonary hypertension associated with hypoxia and structural lung disease.
Olschewski H, Simonneau G, Galie N, et al, for the Aerosolized Iloprost Randomized Study Group. Inhaled Iloprost for Severe Pulmonary Hypertension. N Engl J Med. 2002;342:322-29.
Keywords: Exercise Tolerance, Iloprost, Epoprostenol, Atrial Pressure, Endothelins, Quality of Life, Hypertension, Pulmonary, Vascular Resistance, Dyspnea, Calcium Channel Blockers, Vasodilator Agents
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