Meta-Analysis of Randomized Controlled Trials on the Treatment of Pulmonary Arterial Hypertension

Fengwen Zhang, Junbao Du, Hongfang Jin, Xueying Li
2010 Circulation Journal  
Pulmonary arterial hypertension (PAH) is a severe disease characterized by a progressive increase of pulmonary pressure and resistance leading to right heart failure. Without treatment, the prognosis for patients with significant PAH is poor. Current PAH specific medications, including prostanoids, endothelin receptor antagonists (ERA), and phosphodiesterase 5 (PDE-5) inhibitors, have sought to address the pulmonary vascular endothelial dysfunction and vasoconstriction associated with this
more » ... tion. The recently studied, the medication for PAH consists mainly of iloprost, bosentan and sildenafil. Iloprost is an inhaled prostanoid. Bosentan is a nonselective ERA. And sildenafil is a PDE-5 inhibitor. So the aim of our study is to evaluate the efficacy and safety of treating PAH with inhaled iloprost, oral bosentan and sildenafil. 1 As mentioned by Dr Uthman, because 3 drugs were involved, we could have adopted a Bayesian mixed treatment comparison. 2,3 Mixed treatment comparison meta-analysis is a generalization of standard pair-wise meta-analysis for A vs B trials, to data structures that include, for example, A vs B, B vs C, and A vs C trials. 3 Indeed, there was 1 randomized, double-blind, active comparator study, 4 sildenafil vs bosentan, that has been published up to August 2009, however, these data were inadequate for meta-analysis. In our study, 1 we pooled data from the randomized controlled trials in which patients with PAH were treated with inhaled iloprost and oral bosentan and sildenafil. Among the 11 trials that met the inclusion criteria, 3 presented results on the controlled treatment of PAH with inhaled iloprost and placebo, 3 involved controlled trials on sildenafil and placebo and the other 5 reported controlled trials on bosentan and placebo. We compared the efficacy and safety of the 3 types of drugs to the placebo using meta-analysis. And then we compared the 3 types of drugs using the chi-squared test. The main purpose of our study was to assess the efficacy and safety of iloprost, sildenafil and bosentan compared to placebo in treating patients with PAH, and the conclusion was that the 3 drugs are effective and safe in treating PAH. However, how to chose the 3 drugs and how to evaluate their safety for the patients remains difficult in clinical practice. We are eager to provide some information for clinical doctors, therefore, we just described the result of the chi-squared test. As the results are subject to the bias associated with observational studies, it is necessary to design more trials regarding the comparison between sildenafil and bosentan, bosentan and iloprost, or iloprost and sildenafil, which would be of value to give more detailed conclusions. References 1. He B, Zhang F, Li X, Tang C, Lin G, Du J, et al. Meta-analysis of randomized controlled trials on treatment of pulmonary arterial hypertension. Circ J 2010; 74: 1458 -1464. 2. Caldwell DM, Ades AE, Higgins JP. Simultaneous comparison of multiple treatments: Combining direct and indirect evidence. Br Med J 2005; 331: 897 -900. 3. Lu G, Ades AE. Combination of direct and indirect evidence in mixed treatment comparisons. Stat Med 2004; 23: 3105 -3124. 4. Wilkins MR, Pual GA, Strange JW, Tunariu N, Gin-sing W, Banya WA, et al. Sildenafil versus endothelin receptor antagonist for pulmonary hypertension (SERAPH) study. Am J Respir Crit Care Med 2005; 171: 1292 -1297.
doi:10.1253/circj.cj-10-0685 fatcat:zcnmuaekobgl5btgsoh22q4h7i