Efficacy and safety of sildenafil treatment in pulmonary arterial hypertension: a systematic review.
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.
Department of Respiratory Medicine, West China Medical School and West China Hospital, Sichuan University, No. 3, Guo Xie Xiang, Chengdu, Sichuan 610000, China.
Rong-chun
RC
Wang
Department of Respiratory Medicine, West China Medical School and West China Hospital, Sichuan University, No. 3, Guo Xie Xiang, Chengdu, Sichuan 610000, China.
Fa-ming
FM
Jiang
Department of Respiratory Medicine, West China Medical School and West China Hospital, Sichuan University, No. 3, Guo Xie Xiang, Chengdu, Sichuan 610000, China.
Qiao-ling
QL
Zheng
Department of Respiratory Medicine, West China Medical School and West China Hospital, Sichuan University, No. 3, Guo Xie Xiang, Chengdu, Sichuan 610000, China.
Chun-tao
CT
Li
Department of Respiratory Medicine, West China Medical School and West China Hospital, Sichuan University, No. 3, Guo Xie Xiang, Chengdu, Sichuan 610000, China.
Xia-ying
XY
Peng
Department of Respiratory Medicine, West China Medical School and West China Hospital, Sichuan University, No. 3, Guo Xie Xiang, Chengdu, Sichuan 610000, China.
Chen-yun
CY
He
Department of Respiratory Medicine, West China Medical School and West China Hospital, Sichuan University, No. 3, Guo Xie Xiang, Chengdu, Sichuan 610000, China.
Jian
J
Luo
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.
Zong-an
ZA
Liang
D017079:Exercise Tolerance / Q000187:drug effects; D065627:Familial Primary Pulmonary Hypertension; D006304:Health Status; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D010879:Piperazines / Q000627:therapeutic use*; D011687:Purines / Q000627:therapeutic use; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000627:therapeutic use*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*
D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate
Pulmonary arterial hypertension; Pulmonary hypertension; Sildenafil; Systematic review