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

Abstract

Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp ulmonary 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. Current medication for PAH consists mainly of prostacyclins, endothelin receptor antagonists and phosphodiesterase type 5 (PDE-5) inhibitors. 1 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. 2 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. 3 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, 4-6 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 Meta-Analysis of Randomized Controlled Trials on Treatment of Pulmonary Arterial HypertensionBing He, BSc; Fengwen Zhang; Xueying Li, BSc; Chaoshu Tang; Guosheng Lin; Junbao Du, MD; Hongfang Jin, MD Background: The aim of the present meta-analysis was to evaluate the efficacy and safety of treating pulmonary arterial hypertension (PAH) with inhaled iloprost, oral bosentan and sildenafil.

Comparative Effectiveness of Pharmacologic Interventions for Pulmonary Arterial Hypertension

“…Conventional meta-analyses are limited by estimates between two interventions compared directly with each other, precluding assessment of comparative efficacy and safety of all available interventions. [4][5][6][7] Hence, evidence regarding the best treatment, either alone or in combination, is limited, leaving such decisions to individual clinical judgment. 8,9 A network meta-analysis approach can bridge this gap and guide both clinical decision-making and future research.…”

The PPARγ ligand rosiglitazone attenuates hypoxia-induced endothelin signaling in vitro and in vivo

“…The pathogenesis of PH involves endothelial dysfunction with increased production of vasoconstrictors, e.g., endothelin-1 (ET-1), and reduced production of vasodilators, e.g., prostacyclin and nitric oxide (NO) (5,14). Despite the availability of existing PH therapies that attenuate these derangements, PH morbidity and mortality remains unacceptably high (20,44), indicating an urgent need for novel therapeutic strategies. Recent studies indicate that the nuclear hormone receptor peroxisome proliferator-activated receptor ␥ (PPAR␥), may play an important role in the pathophysiology of PH.…”

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

“…1 The authors concluded that "in terms of clinical worsening and functional class amelioration, insignificant differences were found among iloprost, bosentan and sildenafil, but iloprost had the highest incidence of serious adverse events among the three drugs". 1 We have concerns about the method used in reaching these conclusions.…”