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.