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N Engl J Med. 1998 Jan 29;338(5):273-7.

Reduction in pulmonary vascular resistance with long-term epoprostenol (prostacyclin) therapy in primary pulmonary hypertension.

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1
Section of Cardiology, Rush Medical College, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612-3824, USA.

Abstract

BACKGROUND:

Primary (idiopathic) pulmonary hypertension is a progressive, fatal disease. Conventional therapy with anticoagulant and vasodilator drugs may improve symptoms and survival among selected patients, but there is no evidence that the disease can be reversed.

METHODS:

We evaluated the effects of long-term therapy (i.e., for more than one year) with intravenous epoprostenol (prostacyclin) in patients with advanced primary pulmonary hypertension. The base-line evaluation included an assessment of pulmonary vascular dilation in response to intravenous adenosine. The epoprostenol dose was increased monthly to the maximum tolerated. Long-term therapy was evaluated by measuring improvement in symptoms, exercise capacity, and hemodynamic measures.

RESULTS:

We evaluated 27 patients with primary pulmonary hypertension over a mean (+/-SD) period of 16.7+/-5.2 months. Intravenous adenosine had a variable effect on pulmonary vascular resistance (mean reduction, 27 percent; range, 0 to 56; P<0.001). Epoprostenol therapy was initiated and the rate of infusion was increased by an average of 2.4 ng per kilogram of body weight per minute each month. Twenty-six of the 27 patients had improvement in symptoms and hemodynamic measures, and overall, pulmonary vascular resistance declined by 53 percent to 7.9+/-3.8 resistance units (P<0.001) at the time of restudy. The long-term effects of epoprostenol exceeded the short-term pulmonary vasodilator response to adenosine in all but one patient. Seven of the eight patients who had minimal pulmonary vasodilation in response to adenosine (mean reduction in resistance units, <20 percent) still had a significant reduction in pulmonary vascular resistance when treated with epoprostenol (mean, 39+/-14 percent; P=0.002).

CONCLUSIONS:

In primary pulmonary hypertension, long-term therapy with epoprostenol lowers pulmonary vascular resistance beyond the level achieved in the short term with intravenous adenosine. Epoprostenol appears to have sustained efficacy in this disorder.

PMID:
9445406
DOI:
10.1056/NEJM199801293380501
[Indexed for MEDLINE]
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