, Volume 15, Issue 5, pp 475-483
Date: 07 Aug 2013

Effectiveness and Safety of Phosphodiesterase 5 Inhibitors in Patients with Cardiovascular Disease and Hypertension

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Phosphodiesterase 5 (PDE 5) inhibitors are selective inhibitors of the enzyme PDE 5, which catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP), a potent vasodilator and nitric oxide (NO) donor, to its corresponding metabolites (monophosphates). The enzyme PDE 5 is widely distributed in the body, including the heart and blood vessels. Because of its distribution, it was hypothesized that its inhibition could lead to significant coronary vasodilation, which would benefit patients with coronary artery disease (CAD). This hypothesis led to the development of PDE 5 inhibitors with the first being sildenafil citrate. Subsequent studies with sildenafil in patients with CAD demonstrated a modest cardiovascular effect, but a potent action on penile erection in men, resulting in sildenafil becoming a first-line therapy of erectile dysfunction (ED). Subsequently, two more PDE 5 inhibitors (vardenafil and tadalafil) were developed and approved by the Food and Drug Administration (FDA) for the treatment of ED. Recent studies have shown several pleiotropic beneficial effects of PDE 5 inhibitors in patients with CAD, hypertension, heart failure, pulmonary arterial hypertension, diabetes mellitus and Raynaud’s phenomenon. Side effects and interactions of PDE 5 inhibitors with other drugs have been minimal, with the exception of their coadministration with nitrates, which could lead to severe vasodilation and hypotension and therefore, their coadministration is prohibited. All these pleiotropic cardiovascular effects of PDE 5 inhibitors and their drug interactions will be discussed in this concise review in the context of the American College of Cardiology / American Heart Association guidelines and the recent developments in this field.