Rong-chun Wang1, Fa-ming Jiang1, Qiao-ling Zheng1, Chun-tao Li1, Xia-ying Peng1, Chen-yun He1, Jian Luo1, Zong-an Liang2. 1. Department of Respiratory Medicine, West China Medical School and West China Hospital, Sichuan University, No. 3, Guo Xie Xiang, Chengdu, Sichuan 610000, China. 2. Department of Respiratory Medicine, West China Medical School and West China Hospital, Sichuan University, No. 3, Guo Xie Xiang, Chengdu, Sichuan 610000, China. Electronic address: liangzongan@hotmail.com.
Abstract
BACKGROUND: To evaluate the safety and efficacy of using sildenafil for ≥ 12 weeks to treat pulmonary arterial hypertension (PAH). METHODS: Randomized controlled trials (RCTs) of sildenafil therapy in patients with PAH published through May 2013 were identified by searching PubMed, the Cochrane Library, Embase, relevant websites, and reference lists of relevant studies. Two reviewers independently assessed the quality of the trials and extracted information. RESULTS: Meta-analysis was carried out with subsets of 4 trials involving 545 patients. Sildenafil therapy significantly reduced clinical worsening of PAH compared to placebo (RR 0.39, 95% CI 0.21-0.69) and improved the 6-min walk distance (MD 31.3 m, 95% CI 18.01-44.67), WHO functional class, hemodynamic variables and health-related quality of life (HRQoL). Sildenafil did not, however, improve all-cause mortality (RR 0.29, 95% CI 0.02-4.94) or Borg dyspnea score relative to placebo, nor did it significantly affect the incidence of serious adverse events. In fact, sildenafil was associated with higher total incidence of adverse events, but these additional events were mild to moderate in severity and were tolerable. CONCLUSIONS: Sildenafil therapy lasting ≥ 12 weeks improves multiple clinical and hemodynamic outcomes in patients with PAH, but it appears to have no effect on mortality or serious adverse events. The long-term efficacy and safety of sildenafil therapy in PAH requires further study based on large and well-designed RCTs.
BACKGROUND: To evaluate the safety and efficacy of using sildenafil for ≥ 12 weeks to treat pulmonary arterial hypertension (PAH). METHODS: Randomized controlled trials (RCTs) of sildenafil therapy in patients with PAH published through May 2013 were identified by searching PubMed, the Cochrane Library, Embase, relevant websites, and reference lists of relevant studies. Two reviewers independently assessed the quality of the trials and extracted information. RESULTS: Meta-analysis was carried out with subsets of 4 trials involving 545 patients. Sildenafil therapy significantly reduced clinical worsening of PAH compared to placebo (RR 0.39, 95% CI 0.21-0.69) and improved the 6-min walk distance (MD 31.3 m, 95% CI 18.01-44.67), WHO functional class, hemodynamic variables and health-related quality of life (HRQoL). Sildenafil did not, however, improve all-cause mortality (RR 0.29, 95% CI 0.02-4.94) or Borg dyspnea score relative to placebo, nor did it significantly affect the incidence of serious adverse events. In fact, sildenafil was associated with higher total incidence of adverse events, but these additional events were mild to moderate in severity and were tolerable. CONCLUSIONS:Sildenafil therapy lasting ≥ 12 weeks improves multiple clinical and hemodynamic outcomes in patients with PAH, but it appears to have no effect on mortality or serious adverse events. The long-term efficacy and safety of sildenafil therapy in PAH requires further study based on large and well-designed RCTs.
Authors: Francesca Gorini; Michele Santoro; Anna Pierini; Lorena Mezzasalma; Silvia Baldacci; Elena Bargagli; Alessandra Boncristiano; Maurizia Rossana Brunetto; Paolo Cameli; Francesco Cappelli; Giancarlo Castaman; Barbara Coco; Maria Alice Donati; Renzo Guerrini; Silvia Linari; Vittoria Murro; Iacopo Olivotto; Paola Parronchi; Francesca Pochiero; Oliviero Rossi; Barbara Scappini; Andrea Sodi; Alessandro Maria Vannucchi; Alessio Coi Journal: Front Pharmacol Date: 2022-05-16 Impact factor: 5.988