Some negative results of clinical trials
Unfortunately, there were also a series of negative results of clinical trials. Due to worse clinical outcomes, usage of sildenafil for corrected valvular heart disease and persistent PAH should be avoided,23 and treatment with sildenafil did not reduce pulmonary artery pressures and did not improve heart failure with preserved ejection fraction (HFpEF).24 In addition, adding sildenafil to bosentan did not significantly improve walking distance in Eisenmenger syndrome,25 but did increase saturation at rest. In addition, regular users of PDE5i might have an increased risk for serous retinal detachment, retinal vascular occlusion, and ischemic optic neuropathy.26 No difference was found between placebo and PDE5i among men treated for ED after prostate surgery.27
Moreover, the use of PDE5i links to the increased risk for melanoma and basal cell carcinoma, but not for prostate cancer, and might have chemoprophylaxis effect on colorectal cancer. In fact, there are inadequate data and evidence regarding the role of PDE5i in cancer pathogenesis28 including brain tumors (glioblastoma multiforme),29 regardless of the promising anti-tumor functions of PDE5i (e.g., triggering apoptosis, suppressing tumor cell growth and invasion, and reversing tumor microenvironment immunosuppression in the brain). However, PDE5i has also some promising anti-tumor functions, for example, triggering apoptosis, suppressing tumor cell growth and invasion, and reversing tumor microenvironment immunosuppression in the brain. Herein, the repurposing PDE5i can target cancer-associated fibroblasts induced chemotherapy resistance.30