Cardiovascular effects of phosphodiesterase type 5 inhibitors.
BACKGROUND
Phosphodiesterase type 5 (PDE5) inhibitors are widely used as first-line therapy for erectile dysfunction (ED). Their efficacy and safety combined with an increasing understanding of cyclic guanosine monophosphate (cGMP)-regulated mechanisms have triggered a number of attempts to determine their effects on the cardiovascular system and their potential benefits in cardiovascular conditions.


OBJECTIVE
To review and discuss recent findings regarding the cardiovascular effects of PDE5 inhibitors and to highlight current and future clinical applications beyond ED.


METHODS
Results of preclinical and clinical studies evaluating the cardiovascular effects of PDE5 inhibitors are analyzed and critically put into perspective.


METHODS
Extensive PubMed literature search reviewing relevant data on effects and mechanisms of PDE5 inhibitors on the cardiovascular system.


RESULTS
In recent years, extensive but very heterogeneous preclinical and clinical evidence has been reported. PDE5 inhibition has proven collateral benefits for a multitude of risk factors or diseases associated with or accompanying ED. However, these agents appear to have the potential of expanding their indications. To date, PDE5 inhibition has been shown to be effective for the treatment of idiopathic pulmonary artery hypertension, and sildenafil is approved for this indication. Importantly, accumulating data show that the therapeutic potential extends to the myocardium, the coronary and peripheral arteries, subliclinical inflammation, oxidative stress, thrombosis, neurological recovery, and pathways of fibrosis. Thus, the spectrum of patients who may benefit has expanded to include, for instance, patients with heart failure or coronary artery disease.


CONCLUSIONS
PDE5 inhibitors are an exciting class of drugs with pleiotropic effects. Current or future PDE5 inhibitors are a conceptually attractive therapeutic strategy with potential clinical applications in a variety of cardiovascular conditions.
Vlachopoulos
Charalambos
C
1st Department of Cardiology, Cardiovascular Diseases and Sexual Health Unit, Athens Medical School, Hippokration Hospital, Athens, Greece. cvlachop@otenet.gr
Ioakeimidis
Nikolaos
N
Rokkas
Konstantinos
K
Stefanadis
Christodoulos
C
D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects* / Q000627:therapeutic use; D008133:Long QT Syndrome / Q000139:chemically induced*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009206:Myocardium; D009569:Nitric Oxide / Q000378:metabolism; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D010879:Piperazines / Q000009:adverse effects* / Q000627:therapeutic use; D012307:Risk Factors; D013450:Sulfones / Q000009:adverse effects / Q000627:therapeutic use; D014227:Triazines / Q000009:adverse effects / Q000627:therapeutic use; D000069058:Vardenafil Dihydrochloride; D014665:Vasodilator Agents / Q000009:adverse effects* / Q000627:therapeutic use
D007093:Imidazoles; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D013450:Sulfones; D014227:Triazines; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000069058:Vardenafil Dihydrochloride