Prostacyclin for pulmonary hypertension.
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.


OBJECTIVE
To determine the efficacy of prostacyclin or one of its analogues in idiopathic primary pulmonary hypertension.


METHODS
A search was carried out using the Cochrane controlled clinical trial register.


METHODS
Randomised controlled trials (RCTs) involving patients with primary pulmonary hypertension were selected by two reviewers.


METHODS
Study quality was assessed and data extracted independently by two reviewers. Outcomes were analysed as continuous and dichotomous outcomes, using standard statistical techniques.


RESULTS
Four RCTs were included, all of short duration (8-12 weeks). Three compared intravenous epoprostenol with conventional therapy, two were in PPH (n = 81 and n = 21) and one with pulmonary hypertension in scleroderma (n = 111). One compared intravenous Iloprost with placebo in 14 patients with scleroderma. Exercise capacity improved in patients treated with intravenous epoprostenol (Standardised Mean Difference) 0.69, 95% Confidence Intervals (CI) 0.40, 0.97. Several haemodynamic variables improved in the group treated with epoprostenol; e.g. mean pulmonary artery pressure fell: Weighted Mean Difference -6.3 mmHg (95% CI -3.9, -8.7). Mortality was improved Peto Odds Ratio 0.32 (95% CI 0.13, 0.77), although this effect was not significant when analysed using a more conservative random effects model: Odds Ratio 0.32 (95% CI 0.06, 1.58). Side effects and adverse events related to the indwelling catheter (sepsis and thrombosis) were common.


CONCLUSIONS
Intravenous prostacyclin over 12 weeks improves exercise capacity, NYHA functional class and several cardiopulmonary haemodynamic variables. It may improve mortality.
Paramothayan
N S
NS
Division of Physiological Medicine, St George's Hospital Medical School, Cranmer Terrace, London, UK, SW17 0RE.
Lasserson
T J
TJ
Wells
A U
AU
Walters
E H
EH
D000959:Antihypertensive Agents / Q000627:therapeutic use*; D011464:Epoprostenol / Q000627:therapeutic use*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
D000959:Antihypertensive Agents; D011464:Epoprostenol