Efficacy and safety of sildenafil treatment in pulmonary arterial hypertension: a systematic review

Respir Med. 2014 Mar;108(3):531-7. doi: 10.1016/j.rmed.2014.01.003. Epub 2014 Jan 15.


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.

Keywords: Pulmonary arterial hypertension; Pulmonary hypertension; Sildenafil; Systematic review.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Exercise Tolerance / drug effects
  • Familial Primary Pulmonary Hypertension
  • Health Status
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Piperazines / therapeutic use*
  • Purines / therapeutic use
  • Quality of Life
  • Randomized Controlled Trials as Topic
  • Sildenafil Citrate
  • Sulfones / therapeutic use*
  • Treatment Outcome
  • Vasodilator Agents / therapeutic use*


  • Piperazines
  • Purines
  • Sulfones
  • Vasodilator Agents
  • Sildenafil Citrate