Journal of Hypertension: Open Access

Effects of Phosphodiesterase Type 5 (PDE-5) Inhibitors in the Management of Pulmonary Arterial Hypertension: A Systematic Review and Meta-analysis Pointing on Peak VO2

Abstract

Rutahoile WM, David NM, Angela AP, Abdallah ZH, Xiao Li Zhou, Huang Wei and Lei Han

Background: In settings where new drugs for pulmonary arterial hypertension (PAH) are not possible due to lack of availability and cost; PDE-5 inhibitors such as sildenafil is the drug of choice in the management of PAH. In this study we performed a meta-analysis to evaluate the effects of oral sildenafil in PAH, pointing on peak VO₂ improvement.

Methods: We retrieved randomized controlled trials (RCTs) of the effects of PDE-5 inhibitors, sildenafil in patients with PAH using PubMed, Medline, Embase, Cochrane Library, Google scholar and manual search from 2011 to 2016. Random controlled trials that compared oral sildenafil with placebo were selected. Data for populations, interventions, and outcomes were extracted independently by 2 investigators, and disagreements were resolved by consensus. Quality assessment was performed using the Cochrane risk-of-bias tool.

Results: Four randomized controlled clinical trials including a total of three hundred thirty six patients were identified in the primary analysis, with 51.5% patients in the PDE-5 inhibitors treatment group and 48.5% patients in the placebo group.

Two studies show reduction in statistical significance of mPAP (MD -4.15, 95% CI -17.28 to 8.98; P<0.00001) and PVR (MD -51.27, 95% CI -127.63 to 25.10; P<0.00001. Other three studies shown statistical significance in reduction of mPCWP (MD -2.70, 95% CI -7.14 to 1.75; P<0.0003). Other two studies which accessed the quality of life show no much differences among the two groups (MD 1.18, 95% CI -4.92 to 7.27; P<0.00001). However, all four trials, shown no statistical significant improvement in peak VO2, of patients allocated to PDE-5 inhibitors group, sildenafil compared to the placebo group with heterogeneity (MD 0.61, 95% CI -0.37 to 1.59, P=0.21, I2=34%).

Conclusion: The results of present review suggest that treatment with PDE-5 inhibitors; sildenafil reduced mPAP, PVR and mPCWP but could not significantly improve the peak VO₂.