Cardiovascular Effects of Phosphodiesterase Type 5 Inhibitors

Abstract

Introduction 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. Aim To review and discuss recent findings regarding the cardiovascular effects of PDE5 inhibitors and to highlight current and future clinical applications beyond ED. Main Outcome Measures 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.

Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction

“…Clinical trials and postmarketing data of all PDE5 inhibitors have demonstrated the drugs to be safe in patients with CV disease. Thus, no increase in myocardial infarction rates has been ob- (Vlachopoulos et al, 2009). No PDE inhibitor has adversely affected total exercise time or time to ischemia during exercise testing in men with stable angina.…”

“…The duration of interaction between organic nitrates and PDE inhibitors varies according to the PDE inhibitor and the nitrate. If a patient develops angina while using a PDE inhibitor, other antiangina agents may be used instead of nitroglycerin or until the appropriate time has passed (24 h for sildenafil or vardenafil and 48 h for tadalafil) (Vlachopoulos et al, 2009).…”

Acute effect of sildenafil on inflammatory markers/mediators in patients with vasculogenic erectile dysfunction

“…There are numerous studies suggesting that phosphodiesterase-5 (PDE-5) inhibitors, which are the first-line therapy of ED, might be effective in reversing generalized endothelial dysfunction [6]. Acute treatment with PDE-5 inhibitors showed favorable effects on brachial artery flow-mediated dilatation up to 24 h post-dose in men with [7] and without ED [8] and in patients with coronary artery disease [9] and chronic heart failure [10].…”

“…Furthermore, chronic treatment restores endothelium-dependent relaxations at various sites of the vascular tree, even up to one week after cessation of the treatment [11]. Beneficial acute (sildenafil, vardenafil) and chronic (sildenafil) effects of PDE-5 inhibitors on aortic stiffness and wave reflections in men with ED are also well-known [6,[12][13][14][15].…”

A fully validated method for the determination of vardenafil in blood using gas chromatography/mass spectrometry

“…[1,7] Furthermore, recent studies have shown VDN as an effective agent in penile rehabilitation, decreasing lower urinary tract symptoms from benign prostatic hyperplasia and management of pulmonary hypertension. [5,8,9] The side effects of VDN are the same as with other PDE-5 inhibitors, such as nausea, abdominal pain, abnormal vision, hypotension, tachycardia and rare heart attack. Physicians should advise patients to stop using PDE-5 inhibitors and seek immediate medical attention in the event of a side effect as a safety measure.…”