Background: Primary pulmonary hypertension (PPH) is progressive, resulting in right ventricular failure. Survival seldom exceeds five years. Pulmonary hypertension can be idiopathic or associated with other conditions. It is common in patients with diffuse scleroderma and the CREST syndrome where it is clinically, haemodynamically and prognostically indistinguishable from idiopathic primary pulmonary hypertension. Prostacyclin is a potent vasodilator and inhibitor of platelet aggregation. Iloprost is a chemically stable derivative of prostacyclin with similar biologic properties and can be given orally, by infusion or nebulised.
Objectives: To determine the efficacy of prostacyclin or one of its analogues in idiopathic primary pulmonary hypertension.
Search strategy: A search was carried out using the Cochrane controlled clinical trial register. An update search was conducted on 12th August 2002. Four new trials met the inclusion criteria of the review.
Selection criteria: Randomised controlled trials (RCTs) involving patients with primary pulmonary hypertension or pulmonary hypertension secondary to connective tissue disorders were selected by two reviewers.
Data collection and analysis: Study quality was assessed and data extracted independently by two reviewers. Outcomes were analysed as continuous and dichotomous outcomes, using standard statistical techniques.
Main results: Seven RCTs of short duration (8-12 weeks) were included. Three compared intravenous epoprostenol with conventional therapy. One compared intravenous Iloprost with placebo. One RCT compared oral prostacyclin with placebo, another compared subcutaneous infusion of treprostinil with placebo and a further RCT studied the effects of inhaled iloprost. All the trials showed an improvement in exercise capacity. Cardiopulmonary haemodynamics, dyspnoea scores and symptoms also improved in some of the studies. Side effects and adverse events related to the indwelling catheter (sepsis and thrombosis) were common in intravenous trials. The other routes of administration had less severe side effects.
Reviewer's conclusions: Intravenous prostacyclin or one of its analogues in addition to conventional therapy over 12 weeks appears to improve exercise capacity, NYHA functional class and several cardiopulmonary haemodynamic variables. There is some evidence that other routes of administration of the drug may also be effective with fewer side effects, which were mainly related to the indwelling catheter.