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Meta-Analysis
. 2005 Apr 18;2005(2):CD002994.
doi: 10.1002/14651858.CD002994.pub2.

Prostacyclin for pulmonary hypertension in adults

N S Paramothayan  1 , T J Lasserson, A U Wells, E H Walters
Affiliations
Meta-Analysis

Prostacyclin for pulmonary hypertension in adults

N S Paramothayan et al. Cochrane Database Syst Rev. .

Abstract

Background: Primary pulmonary hypertension (PPH) is progressive, resulting in right ventricular failure. Pulmonary hypertension can be idiopathic or associated with other conditions. Prostacyclin is a potent vasodilator and inhibitor of platelet aggregation, and can be given orally, subcutaneously, intravenously or inhaled via a nebuliser.

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

Search strategy: Electronic searches were carried out with pre-specified terms. Searches were current as of July 2004.

Selection criteria: Two reviewers selected randomised controlled trials (RCTs) involving adults with pulmonary hypertension for inclusion.

Data collection and analysis: Study quality was assessed and data extracted independently by two reviewers. Outcomes were analysed as continuous and dichotomous outcomes. We sub-grouped data where possible by aetiology of PH (PPH, PH secondary to connective tissue disorder or mixed populations).

Main results: Nine RCTs of mixed duration (3 days-52 weeks), recruiting 1175 participants were included (NYHA functional classes II-IV). Intravenous prostacyclin versus usual care (four studies): There were significant improvements in exercise capacity of around 90 metres, cardiopulmonary haemodynamics and NYHA functional class over 3 days-12 weeks. Effects were consistent in primary and secondary pulmonary hypertension. Oral prostacyclin versus placebo (two studies): Short-term data (3-6 months) indicated that there was a significant improvement in exercise capacity, but data from one study of 52 weeks reported no significant difference at 12 months. No significant differences were observed for any other outcome. Subcutaneous treprostinil versus placebo (two studies, 8-12 weeks):One large study reported a significant median improvement in exercise capacity of around 16 metres. Cardiopulmonary haemodynamics and symptom scores favoured treprostinil. Infusion site pain and withdrawals due to adverse events were more frequent with treprostinil. Inhaled prostacyclin versus placebo (one study, 12 weeks):There was a significant increase in exercise capacity of approximately 36 metres. Treatment led to better symptom scores and functional class status than with placebo. Subgroup analyses reported by individual studies showed a better exercise capacity in participants with PPH, than those participants with PH secondary to other diseases. Side effects and adverse events were common in the studies.

Authors' conclusions: There is evidence that intravenous prostacyclin in addition to conventional therapy at tolerable doses optimised by titration, can confer some short-term benefits (up to 12 weeks of treatment) in exercise capacity, NYHA functional class and cardiopulmonary haemodynamics. There is also some evidence that patients with more severe disease based upon NYHA functional class showed a greater response to treatment.

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Conflict of interest statement

None known

Figures

1
1
Forest plot of comparison: 1 Intravenous prostacyclin versus usual care, outcome: 1.1 Exercise capacity (metres walked in six minutes).
2
2
Forest plot of comparison: 1 Intravenous prostacyclin versus usual care, outcome: 1.7 Improvement in NYHA.
3
3
Forest plot of comparison: 5 Oral beraprost versus placebo, outcome: 5.2 Improvement in functional class.
1.1
1.1. Analysis
Comparison 1 Intravenous prostacyclin versus usual care, Outcome 1 Exercise capacity (metres walked in six minutes).
1.2
1.2. Analysis
Comparison 1 Intravenous prostacyclin versus usual care, Outcome 2 Improvement in NYHA.
1.3
1.3. Analysis
Comparison 1 Intravenous prostacyclin versus usual care, Outcome 3 Change in mean pulmonary artery pressure (mm Hg).
1.4
1.4. Analysis
Comparison 1 Intravenous prostacyclin versus usual care, Outcome 4 Change in pulmonary vascular resistance (mm Hg/l/min).
1.5
1.5. Analysis
Comparison 1 Intravenous prostacyclin versus usual care, Outcome 5 Change in cardiac index (l/min/m2).
1.6
1.6. Analysis
Comparison 1 Intravenous prostacyclin versus usual care, Outcome 6 Change in cardiac output (L/min).
1.7
1.7. Analysis
Comparison 1 Intravenous prostacyclin versus usual care, Outcome 7 Mortality.
1.8
1.8. Analysis
Comparison 1 Intravenous prostacyclin versus usual care, Outcome 8 Change in systemic arterial oxygen saturation (%).
1.9
1.9. Analysis
Comparison 1 Intravenous prostacyclin versus usual care, Outcome 9 Change in systemic oxygen transport (ml/min).
2.1
2.1. Analysis
Comparison 2 Introvenous iloprost versus usual care, Outcome 1 DLco (ml/min/ml/Hg).
2.2
2.2. Analysis
Comparison 2 Introvenous iloprost versus usual care, Outcome 2 Vital capacity (l).
3.1
3.1. Analysis
Comparison 3 Inhaled iloprost versus placebo, Outcome 1 Exercise capacity: Participants achieving >10% increase.
3.2
3.2. Analysis
Comparison 3 Inhaled iloprost versus placebo, Outcome 2 Exercise capacity: Participants with < and >10% change.
3.3
3.3. Analysis
Comparison 3 Inhaled iloprost versus placebo, Outcome 3 Exercise capacity (change from baseline).
3.4
3.4. Analysis
Comparison 3 Inhaled iloprost versus placebo, Outcome 4 NYHA Functional class ‐ participants with improvement.
3.5
3.5. Analysis
Comparison 3 Inhaled iloprost versus placebo, Outcome 5 NYHA Functional class ‐ participants with no improvement.
3.6
3.6. Analysis
Comparison 3 Inhaled iloprost versus placebo, Outcome 6 Mean PAP (change from baseline).
3.7
3.7. Analysis
Comparison 3 Inhaled iloprost versus placebo, Outcome 7 PVR (change from baseline).
3.8
3.8. Analysis
Comparison 3 Inhaled iloprost versus placebo, Outcome 8 Cardiac output.
3.9
3.9. Analysis
Comparison 3 Inhaled iloprost versus placebo, Outcome 9 Dyspnoea score.
3.10
3.10. Analysis
Comparison 3 Inhaled iloprost versus placebo, Outcome 10 Mortality.
3.11
3.11. Analysis
Comparison 3 Inhaled iloprost versus placebo, Outcome 11 Quality of life.
3.12
3.12. Analysis
Comparison 3 Inhaled iloprost versus placebo, Outcome 12 Clinical deterioration.
3.13
3.13. Analysis
Comparison 3 Inhaled iloprost versus placebo, Outcome 13 Adverse effects (all aetiologies ‐ subgrouped by type of event).
4.1
4.1. Analysis
Comparison 4 Subcutaneous treprostinil versus placebo, Outcome 1 Exercise capacity.
4.2
4.2. Analysis
Comparison 4 Subcutaneous treprostinil versus placebo, Outcome 2 Change in exercise capacity (metres walked).
4.4
4.4. Analysis
Comparison 4 Subcutaneous treprostinil versus placebo, Outcome 4 Change in Dyspnea score.
4.5
4.5. Analysis
Comparison 4 Subcutaneous treprostinil versus placebo, Outcome 5 Mean PAP (change from baseline).
4.6
4.6. Analysis
Comparison 4 Subcutaneous treprostinil versus placebo, Outcome 6 PVR (change from baseline).
4.7
4.7. Analysis
Comparison 4 Subcutaneous treprostinil versus placebo, Outcome 7 Cardiac index (change from baseline).
4.8
4.8. Analysis
Comparison 4 Subcutaneous treprostinil versus placebo, Outcome 8 Mortality.
4.9
4.9. Analysis
Comparison 4 Subcutaneous treprostinil versus placebo, Outcome 9 Quality of life.
4.10
4.10. Analysis
Comparison 4 Subcutaneous treprostinil versus placebo, Outcome 10 Dyspnoea score.
4.11
4.11. Analysis
Comparison 4 Subcutaneous treprostinil versus placebo, Outcome 11 Withdrawals due to clinical deterioration.
4.12
4.12. Analysis
Comparison 4 Subcutaneous treprostinil versus placebo, Outcome 12 Withdrawals due to drug related adverse events.
4.13
4.13. Analysis
Comparison 4 Subcutaneous treprostinil versus placebo, Outcome 13 Side effects (all aetiologies ‐ subgrouped by type of AE).
5.1
5.1. Analysis
Comparison 5 Oral beraprost versus placebo, Outcome 1 Exercise capacity (metres).
5.2
5.2. Analysis
Comparison 5 Oral beraprost versus placebo, Outcome 2 Improvement in functional class.
5.3
5.3. Analysis
Comparison 5 Oral beraprost versus placebo, Outcome 3 Mean PAP (change from baseline in mmHg).
5.4
5.4. Analysis
Comparison 5 Oral beraprost versus placebo, Outcome 4 PVR (change from baseline in mmHg/L/min/m2).
5.5
5.5. Analysis
Comparison 5 Oral beraprost versus placebo, Outcome 5 Cardiac index.
5.6
5.6. Analysis
Comparison 5 Oral beraprost versus placebo, Outcome 6 Mortality.
5.7
5.7. Analysis
Comparison 5 Oral beraprost versus placebo, Outcome 7 Quality of life.
5.8
5.8. Analysis
Comparison 5 Oral beraprost versus placebo, Outcome 8 Dyspnoea score.
5.9
5.9. Analysis
Comparison 5 Oral beraprost versus placebo, Outcome 9 Clinical deterioration.
5.10
5.10. Analysis
Comparison 5 Oral beraprost versus placebo, Outcome 10 Withdrawals due to adverse events.
5.11
5.11. Analysis
Comparison 5 Oral beraprost versus placebo, Outcome 11 Cardiac Index.
5.12
5.12. Analysis
Comparison 5 Oral beraprost versus placebo, Outcome 12 Exercise capacity (mean change from baseline).
5.13
5.13. Analysis
Comparison 5 Oral beraprost versus placebo, Outcome 13 Side‐effects (all aetiologies subgrouped by type of event).
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Update of

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Olschewski 1996 {published data only}
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