title: PDE5 inhibitor sildenafil in the treatment of heart failure: a meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  Clinical trials have evaluated the use of phosphodiesterase (PDE) 5 inhibitors sildenafil as a potential adjunct in the treatment of heart failure (HF) with mixed results. Thus, we undertook a meta-analysis to evaluate the clinical viability of sildenafil in HF.
  
  
  METHODS
  Relevant studies were searched and identified in the MEDLINE and EMBASE databases. Randomized clinical trials (RCT) comparing sildenafil to placebo, in heart failure patients, reporting at least one outcome of interest were included. Data were extracted regarding the characteristics and clinical outcomes.
  
  
  RESULTS
  We identified 9 RCTs enrolling 612 HF patients. There were no significant differences in adverse events between sildenafil group and placebo group (RR=1.10, 95% CI=0.74 to 1.65, P=0.41), whereas sildenafil therapy was associated with a marked improvement in hemodynamic parameter peak VO2 (MD=3.25, 95% CI=2.07 to 4.42, P<0.00001) in HF with reduced ejection fraction (HFrEF) patients but not in HF with preserved ejection fraction (HFpEF) patients. Also, sildenafil therapy improved VO2 at anaerobic threshold (AT) (MD=3.47, 95% CI=1.68 to 5.27, P=0.0002), VE/VCO2 slope (MD=-7.06, 95% CI=-8.93 to -5.19, P<0.00001) and LV ejection fraction (MD=5.43, 95% CI=3.66 to 7.20, P<0.00001) compared to placebo in HF patients, which had no impact on blood pressure and heart rate. For quality of life (emotional function, fatigue and breathlessness), there was no significant difference between the two groups.
  
  
  CONCLUSIONS
  Sildenafil improved hemodynamic parameters particularly in HFrEF patients when compared to placebo, with no increase in adverse events. Sildenafil treatment was well tolerated and had no impact on quality of life.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, PR China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zhuang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Long
authors.affiliation: Grade 2009, Clinical Medicine Eight Years, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, PR China.
authors.forename: Xun
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, PR China. Electronic address: liaoxinx@mail.sysu.edu.cn.
authors.forename: Xin-Xue
authors.initials: XX
authors.lastname: Liao
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, PR China. Electronic address: zsy.dzm@gmail.com.
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Du
mesh_terms: D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D011687:Purines / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000627:therapeutic use*; D020257:Ventricular Remodeling
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate
keywords: Heart failure; Meta-analysis; Phosphodiesterase; Randomized controlled trial; Sildenafil