Prostacyclin and its analogues in pulmonary artery hypertension: a meta-analysis

Abstract

Objective:

Individual studies examining the effects of prostacyclin and its analogues on pulmonary artery hypertension (PAH) have reported controversial results. This study aims to evaluate the efficacy of these agents for PAH by a meta-analysis based on randomized controlled trials (RCTs).

Research design and methods:

We systematically searched Pubmed, MEDLINE, EMBASE, ISI Web of Science, and the Cochrane Library through April 2012. All published RCTs reporting the effects of treatment with prostacyclin or its analogues in PAH were included. Summary statistics were calculated using a random effects model.

Results:

A total of 14 RCTs with 1606 participants were analyzed. Overall, prostacyclin and its analogues increased 6-minute walk distance (6-MWD) (weighted mean differences [WMD] = 18.78 meters, 95% confidence interval [CI]: 11.21 to 26.35; p < 0.01) and improved NYHA functional class status (odds ratios [OR] = 3.98, 95% CI: 1.70 to 9.34; p = 0.001) compared with the control. Moreover, these agents led to statistically significant reductions in mean pulmonary artery pressure (mPAP) (WMD = −4.63 mmHg, 95% CI: −6.81 to −2.44; p < 0.01) and pulmonary vascular resistance (PVR) (standardized mean difference [SMD] = −0.69, 95% CI: −0.96 to −0.43; p < 0.01). Notably, there were distinct effects on these endpoints observed in pooled subgroup analyses based on agent class (all p for interaction < 0.01). In addition, PAH-specific therapy appeared to have superiority over the control in reducing the incidence of all-cause death (OR = 0.49, 95% CI: 0.26 to 0.94; p = 0.03). However, there existed a substantial publication bias, which appeared to markedly impact the overall result of 6-MWD.

Conclusions:

PAH-specific treatment with prostacyclin and its analogues significantly improved exercise capacity, cardiopulmonary hemodynamics, and lowered all-cause mortality in patients with PAH.

Keywords::

• Analogues
• Meta-analysis
• Prostacyclin
• Pulmonary artery hypertension

Transparency

Declaration of funding

This work was not funded by an industry sponsor.

Declaration of financial/other relationships

T.L., W.Z., Y.C., N.G., S.M. and X.L. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

T.L. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The study concept and design was carried out by T.L. Data collection was carried out by W.Z. and Y.C. Data analysis/interpretation was carried out by T.L., N.G. and S.M. T.L., W.Z. and Y.C. drafted the article. S.M. and X.L. carried out critical revision of the article. All authors approved the submitted and final versions.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgements

None.