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