Meta-Analysis Of Randomized Controlled Trialson Treatment Of Pulmonary Arterial Hypertension

Background:Pulmonary arterial hypertension (PAH) is a chronic and severe fatal disease that can be secondary to the cardiac, pulmonary or systemic diseases or unexplained. Studies on PAH have been carried out for more than 100 years, but therapeutic measures remain limited.Meta-analysis is a statistical technique for summarising, amalgamating, and reviewing previous quantitative research. A wide variety of questions can be investigated by using meta-analysis, as long as a reasonable body of primary research studies exist. Selected parts of the reported results of primary researchs are entered into a database, and this "meta-data" is "meta-analyzed", in similar ways to working with other data-descriptively and then inferentially to test certain hypotheses. Meta-analysis has been used to give helpful insight into the overall effectiveness of interventions, the relative impact of independent variables, and the strength of relationship between variables.Current medication for PAH consists mainly of prostacyclins, endothelin receptor antagonists and phosphodiesterase type 5 (PDE-5) inhibitors.Bosentan is a non-selective endothelin receptor antagonist that has been approved by the US Food and Drug Administration (FDA) for patients in World Health Organization (WHO) functional class III or IV to ameliorate exercise capacity and decrease the rate of clinical worsening. Sildenafil is a PDE-5 inhibitor, which has been approved by the US FDA for the treatment of PAH to improve exercise ability.Iloprost is an inhaled prostacyclin drug that can act on the pulmonary blood vessels selectively and improve the hemodynamics of patients with PAH effectively; in addition, compared with traditional prostacyclin drugs, it has a longer halflife and can be administered by aerosol inhalation, avoiding the occurrence of infections, deep venous thrombosis, catheter displacement or pneumothorax resulting from previous iv medication. These drugs can alleviate the symptoms in patients with PAH, and improve exercise capacity, hemodynamics and outcome. The clinical relevance of these effects, however, has been recently challenged, mainly because of the limited amelioration of exercise capacity by medication, short duration and the small size of the individual studies, which have precluded any insight into the prognostic relevance of the treatments.Thus in the present study randomized controlled trails on treating PAH with inhaled iloprost and oral bosentan and sildenafil were collected to quantitatively analyze and compare the efficacy and safety of treating PAH using the 3 kinds of drugs, with a view to arrive at more credible conclusions and lay the theoretical foundation for the treatment of PAH.Methods:The randomized controlled trials on the three drugs and placebo were retrieved in the database Cochrane Central Register of Controlled Trials (CENTRAL), medline, Embase, National Technical Information Service (NTIS), biosispreviews and CNKI, VIP, Wanfang Data up to August 2009. The search term used by "bosentan or sildenafil or iloprost and pulmonary hypertension". Manual retrieval, including retrieving the compilation of academic conference articles and dissertations,was used to collect the data related to medication of PAH as comprehensively as possible. After retrieval the included studies were subjected to quality evaluation in line with the Juni scale,and divided into A, B, C three levels.The situation of clinical worsening, New York Heart Assocation(NYHA)/WHO functional class,6-min walk test (6MWT), and hemodynamic parameters including systolic pulmonary arterial pressure, mean pulmonary arterial pressure, pulmonary vascular resistance, cardiac output and cardiac index, were applied to evaluate the efficacy of drugs. The selected research studies were analyzed using the statistical software Revman 4.2.Results:A total of 1,894 studies were retrieved using the aforementioned retrieval methods, among which Chinese literature were 1009 and English literature were 885. Eliminate duplication and overlapping published literature and clearly does not meet the inclusion criteria of the literature 1851. After reading the text title and summary, controlled clinical study were reduced into the 43. Text, which excluded non-randomized controlled trials and no controlled clinical trials and is really impossible to determine whether the RCT articles, were 32. The final included 11 meeting the inclusion criteria were screened. There was no Chinese literature,11 papers are all in English. In total, 1,391 PAH patients were included, consisting of 822 patients in the medication group and 569 patients in the placebo group. Among the 11 included studies,6 met grade A criteria of quality evaluation on the Juni scale,4 met grade B and 1 met grade C.Compared with placebo, iloprost, bosentan and sildenafil reduced clinical worsening significantly, with the odds ratio (OR) of 0.33 and 95% confidence interval (CI) of 0.22-0.49 (P< 0.00001), increased the six-minute walk distance by 33.19 m, reduced systolic pulmonary arterial pressure, mean pulmonary arterial pressure and pulmonary vascular resistance, increased the cardiac index by 0.40 L/min/m2 and increased the cardiac output by 0.53 L/min.The incidence of severe adverse was lower in the medication groups than the placebo group, with the OR of 0.92 (95% CI of 0.66-1.27, P= 0.61). In terms of the clinical worsening and cardiac function amelioration, insignificant differences were found among inhaled iloprost, oral bosentan and oral sildenafil, but sildenafil had the lowest incidence of severe adverse reactions among the three drugs.ConclusionInhaled iloprost and oral bosentan and sildenafil are all effective in treating pulmonary arterial hypertension, but sildenafil has the lowest incidence of severe adverse reactions among the three drugs.