Conclusions and future perspectives
All in all, people expect PDE5i being more and better applied in clinical practice for CVD, but large-scale clinical trials are needed to indicate the clinical efficacy and practical applications of PDE5i. For example, we can apply excellent MR methods to discover more and better agents, therefore, better serving human health. In fact, as poly-pharmacological strategies for human health care, the E(e)SEEDi or the “magic polypill”,31 newly referred to as “Vitamin CH” or “Vitamin C2”, and “Hot Pots” of both traditional Chinese and marine natural products,32,33 may greatly improve clinical outcomes of both major non-communicable diseases and virus-infectious diseases. This means that if combining with healthy lifestyle and TCM, there will be more benefits from the use of PDE5i.
Currently, the intersection between cardiovascular and sexual health remains a vital topic,34 and data on safety of PDE5i, drug-drug interactions, and a potential cardioprotective effect of these PDE5i drugs are increasing. Previous studies confirmed that PDE5i treatment for ED was associated with a decreased risk of AMI and CVD for the first 3 years.35 Beyond most successful PDE5i for ED, the development of PDE3i for CHF and PDE4i for inflammatory airways disease have good prospects. Since PDE5 inhibition might be used as an effective strategy and a therapeutic candidate for the treatment of Alzheimer’s disease (AD),36,37 the development of agents of PDE5i with improved pharmacologic profile (e.g. higher potency, improved selectivity, and blood-brain barrier penetration) is also promising.
Other uses of PDE5i in clinical disorders include diabetic patients, treatment of Raynaud phenomenon38 and COVID-19 infection. In addition, sildenafil therapy may reduce dyspnea in Eisenmenger syndrome by the role of J receptors,39 the use of PDE5 inhibitors greatly increased (20-fold) among patients with IHD who were taking nitrates.40 PDE5i may have cardiorenal protective effects with sex- and tissue-specific responses in diabetic cardiomyopathy.41 Further high-quality research is warranted to confirm these findings and elucidate the underlying mechanisms.