PDE5 inhibitor sildenafil in the treatment of heart failure: A meta-analysis of randomized controlled trials

• Published in: International journal of cardiology 2014-04, Vol.172 (3), p.581-587
• Main Authors: Zhuang, Xiao-Dong, Long, Ming, Li, Fei, Hu, Xun, Liao, Xin-Xue, Du, Zhi-Min
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cardiology. Vascular system; Cardiovascular; Heart; Heart failure; Heart Failure - drug therapy; Heart Failure - physiopathology; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Humans; Medical sciences; Meta-analysis; Phosphodiesterase; Phosphodiesterase 5 Inhibitors - therapeutic use; Piperazines - therapeutic use; Purines - therapeutic use; Randomized controlled trial; Randomized Controlled Trials as Topic; Sildenafil; Sildenafil Citrate; Sulfones - therapeutic use; Ventricular Remodeling
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2014.01.102

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.