Major clinical applications and related molecular mechanisms
So far, millions of patients with CVD are prescribed PDE5i for
ED.8 PDE5i treatment may reduce mortality after AMI in
men with stable coronary artery disease (CAD),9 with
lower risks of death, recurrence of AMI, congestive heart failure (CHF),
and revascularization. The use of PDE5i links to a lower risk for
cardiovascular events and overall mortality.4 Oral
administration of a single dose of sildenafil improves exercise capacity
and haemodynamic response to exercise in Fontan
patients.10
Since ED is a frequent complication of CHF and stroke, as well as a
possible predictor of cardiovascular events and mortality, treatment of
ED in CHF patients should be individualized and multidisciplinary. As
the first-line therapy for ED, pulmonary artery hypertension (PAH), and
lower urinary tract symptoms, PDE5i may improve both sexual function,
cardiopulmonary parameters,11 and the other clinical
outcome. And PDE5i use was also associated with lower mortality and
ischemic strokes after device implantation (such as left ventricular
assist devices).12
As to combination treatment, both initial combination (e.g., tadalafil
and ambrisentan)13 or a fixed-dose combination (e.g.,
tadalafil and others) of PDE5i in a once-daily, single tablet could
improve significantly clinical outcomes vs monotherapies in PAH
patients with a safety and tolerability profile14 due
to related molecular mechanisms (Table 1). However, the use of a PDE5i
in combination with nitrate medication in men with stable CAD may pose
an increased risk for cardiovascular morbidity and
mortality.15 Long-term tolerability of PDE5i is good.
Particularly, sildenafil, a selective PDE5i, is well tolerated in its
intravenous and oral forms, and did not adversely affect any exercise
parameter in men with CAD and ED.