Main Organiser

Julius Centre University of Malaya

Co-organiser

Department of Social and Preventive Medicine, Faculty of Medicine, University of Malay

Supported by

University of Malaya

TO EVALUATE THE EFFICACY OF BOSENTAN AND SILDENAFIL IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION

Author

Su HC, Wang HY

Institution

Department of Pharmacy, Chi-Mei Medical Center, Tainan, Taiwan

Abstract

Objectives: The objective of this study was to evaluate the efficacy and safety of bosentan and sildenafil in the treatment of patients with PAH.

Methods: Search was conducted of English- language articles using the MEDLINE database (1966-2012), Cochrane Central Register of Controlled Trials, EMBASE (1980-2012), PubMed (1980-2012). Only bosentan and sildenafil clinical studies in patients with PAH were included in the analysis, with a focus on randomized double-blind studies. Adults and children diagnosis of PAH was based on clinical symptoms with pulmonary and cardiac imaging and, ideally, the results of right- heart catheterisation. Studies with pulmonary hypertension (PH) patients as participants secondary to other diseases were included if there was available data assessing the outcomes specific to patients with PAH. Outcome measures primary end-point included borg dyspnoea index, 6-minute walk distance (6MWD). We extracted data from the included trials into RevMan 5.0.

Results: Six double-blind randomized control trials were fit to our study (three bosentan and three sildenafil). In bosentan studies, the Borg index (95% CI -0.34 to 0.2), 6MDW (95% CI -0.45 to 0.04), pulmonary vascular resistance (95% CI -0.03 to 0.45), and cardiac index (95% CI -0.2 to 0.28) were no difference between treatment and placebo groups. In sildenafil studies, 6MWD was slightly lower than that in participants with bosentan (95% CI -0.19 to 0.5). These results might due to sample size lead to have significant heterogeneity.

Conclusion: These index (exercise capacity, hemodynamics parameters) were no signficant difference between bosentan and sildenafil. However, only four small trials favored treatment group, sildenafil, but the sample size and the results should be interpreted with caution. Consider the cost may sildenafil as the first line to treatment PAH. A pharmacokinetic interaction between these two drugs indicates that such combinations need careful pharmacodynamic evaluation. Combination therapy with these two drugs with different mechanisms of action may provide greater efficacy than monotherapy, but that needed to be determinated.