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

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.