Elsevier

Urology

Volume 68, Issue 3, Supplement, September 2006, Pages 47-60
Urology

Cardiovascular safety of sildenafil citrate (Viagra®): An updated perspective

https://doi.org/10.1016/j.urology.2006.05.047Get rights and content

Abstract

Sildenafil citrate (Viagra®; Pfizer Inc, New York, NY) relaxes vascular smooth muscle, resulting in modest reductions in blood pressure that are insufficient to stimulate a reflex increase in heart rate. These blood pressure reductions are similar for healthy men and men with coronary artery disease (CAD) or who use antihypertensive drugs. Sildenafil does not affect the force of cardiac contraction, and cardiac performance is unaffected. Sildenafil is mildly vasodilating in the coronary circulation and does not increase the risk of ventricular arrhythmia. During exercise and recovery, sildenafil does not cause clinically significant alterations in hemodynamic parameters in men with CAD, and it has no negative effects on coronary oxygen consumption, ischemia, or exercise capacity. Clinical trial data from >13,000 patients, 7 years of international postmarketing data, and observational studies of >28,000 men in the United Kingdom and 3813 men in the European Union reveal that (1) there are no special cardiovascular concerns when sildenafil is used in accordance with product labeling and (2) the risk for serious events such as myocardial infarction or death is not increased. However, because safety has not been established in patients with recent serious cardiovascular events, hypotension or uncontrolled hypertension, or retinitis pigmentosa, physicians should consult their current local prescribing information before prescribing sildenafil for these patients. Among men with erectile dysfunction treated with sildenafil, the adverse event profile is similar overall to that in men with comorbid cardiovascular disease (CVD), it is similar between those with and without CAD, and it is similar between those who take and those who do not take antihypertensive drugs (regardless of the number or class). In a controlled interaction study of sildenafil and amlodipine, the mean additional reduction in supine blood pressure was 8 mm Hg systolic and 7 mm Hg diastolic. Sildenafil should be used with caution in patients who take α-blockers because coadministration may lead to symptomatic hypotension in some individuals. When sildenafil is coadministered with an α-blocker, patients should be stable on α-blocker therapy before initiating sildenafil treatment and sildenafil should be initiated at the lowest dose. Also, in the absence of information specific to mixed α/β blockers, such as carvedilol and labetalol, similar care should be taken as for α-blockers. Sildenafil potentiates the hypotensive effects of nitrates, and its administration to patients who are using organic nitrates in any form, either regularly or intermittently, is contraindicated. Before prescribing sildenafil, physicians should carefully consider whether their patients with underlying CVD could be affected adversely by resuming sexual activity. Management recommendations based on cardiovascular risk, from the Second Princeton Consensus Conference, are presented.

Section snippets

General cardiovascular effects of sildenafil

The cardiovascular effects of sildenafil are mediated primarily by means of its relaxant effect on vascular smooth muscle, which causes vasodilation. Sildenafil was originally developed as an antianginal therapy but proved to be no more effective than nitrates.8 PDE5, which is plentiful in vascular smooth muscle,9 is inhibited by sildenafil, thereby increasing levels of cyclic guanosine monophosphate (cGMP).10, 11 Intracellular levels of cGMP affect numerous cellular functions, with protein

Cardiovascular safety of sildenafil during treatment of patients with erectile dysfunction

The cardiovascular safety of sildenafil in the treatment of patients with ED has been assessed in tens of thousands of individuals worldwide. Data were pooled from up to 37 phase 2, 3, and 4 clinical trials of men with ED who received sildenafil (N = 4405) or placebo (N = 3945). These data enabled calculation of the adverse event profile, including cardiovascular adverse events, in the sildenafil clinical trial population of men with ED1, 37 and in subpopulations with concomitant CVD1 or CAD,38

Conclusions

Men with ED tend to be at increased risk for cardiovascular events because of shared risk factors with CVD. In the 2 hours after sexual activity, the relative risk of MI is increased 2.5-fold in men without a history of cardiac disease and 2.9-fold in those with a history of cardiac disease, although the absolute risk is low (0.9%).51 However, no evidence suggests that the use of sildenafil is associated with an increased risk for cardiovascular events. The sildenafil adverse event profile,

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      Sildenafil acts as a phosphodiesterase-5 selective inhibitor, leading to extended GMPc lifetime and consequent longer erections [2,4]. Sildenafil revolutionized erectile dysfunction (ED) treatment due to its advantageous pharmacokinetics characteristics and is also indicated to treat other conditions, such as neuroinflammation, rheumatoid arthritis, pulmonary hypertension, hepatic fibrosis, benign prostate hyperplasia, chronic cardiac diseases, ischemia, hypertension and chronic kidney diseases [5–11]. Despite the benefits, sildenafil adverse effects listed in the literature include headaches, redness, small blood pressure falls, visual alterations, dyspepsia, nasal congestion, urinary tract infections, priapism, melanoma, recurrence of prostate cancer, light sensitivity and dizziness [1,12,13].

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    Graham Jackson and Melvin D. Cheitlin are consultants to, and meeting participants and lecturers for, Pfizer Inc.

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