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.