Review
Sexual Dysfunction and Cardiac Risk (the Second Princeton Consensus Conference)

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Recent studies have highlighted the relation between erectile dysfunction (ED) and cardiovascular disease. In particular, the role of endothelial dysfunction and nitric oxide in ED and atherosclerotic disease has been elucidated. Given the large number of men receiving medical treatment for ED, concerns regarding the risk for sexual activity triggering acute cardiovascular events and potential risks of adverse or unanticipated drug interactions need to be addressed. A risk stratification algorithm was developed by the First Princeton Consensus Panel to evaluate the degree of cardiovascular risk associated with sexual activity for men with varying degrees of cardiovascular disease. Patients were assigned to 3 categories: low, intermediate (including those requiring further evaluation), and high risk. This consensus study from the Second Princeton Consensus Conference corroborates and clarifies the algorithm and emphasizes the importance of risk factor evaluation and management for all patients with ED. The panel reviewed recent safety and drug interaction data for 3 phosphodiesterase (PDE)-5 inhibitors (sildenafil, tadalafil, vardenafil), with emphasis on the safety of these agents in men with ED and concomitant cardiovascular disease. Increasing evidence supports the role of lifestyle intervention in ED, specifically weight loss and increased physical activity, particularly in patients with ED and concomitant cardiovascular disease. Special management recommendations for patients taking PDE-5 inhibitors who present at the emergency department and other emergency medical situations are described. Finally, further research on the role of PDE-5 inhibition in treating patients with other medical or cardiovascular disorders is recommended.

Section snippets

Management Recommendations

Consensus statements were formulated by the panel after the presentation of each topic by a senior investigator, discussion of the research findings, and review of previous recommendations. The final preparation and modifications of the consensus study were made by electronic communication. The final recommendations were approved by a unanimous consensus of the panel. The participants reaffirmed the value and applicability of the original guidelines and the Princeton stratification algorithm.

Asymptomatic, <3 cardiovascular risk factors

Patients with <3 major risk factors for cardiovascular disease (excluding gender) are generally at low risk for significant cardiac complications from sexual activity or the treatment of sexual dysfunction (Table 1). These patients are usually good candidates for pharmacologic and nonpharmacologic treatments for ED.

Controlled hypertension

Patients whose blood pressure is well controlled with ≥1 antihypertensive medication may safely receive approved medical therapies for sexual dysfunction. However, β blockers and

High-Risk Patients

The high-risk category consists of patients whose cardiac conditions are sufficiently severe and/or unstable that sexual activity may pose a significant risk. Most such patients are moderately to severely symptomatic. High-risk patients should be referred for cardiologic assessment and treatment. Sexual activity should be deferred until a patient’s cardiac condition has been stabilized by treatment or a decision has been made by a cardiologist and/or internist that sexual activity may be safely

Intermediate- or Indeterminate-Risk Patients

Patients whose cardiac conditions are uncertain, as well as those with multiple risk factors, require further testing or evaluation before resuming sexual activity. On the basis of results of this evaluation, these patients may be subsequently classified as either at high or low risk from sexual activity. Cardiology consultation may be of value in some cases to assist primary physicians in assessing the risk of sexual activity for patients as follows.

Final Algorithm for Risk Stratification and Patient Management

Figure 1 shows a simplified algorithm for cardiovascular risk stratification and patient management. This algorithm views the assessment and management of patients with possible ED as a 3-step process.

Overall safety

Controlled and postmarketing studies of the US Food and Drug Administration-approved PDE-5 inhibitors (sildenafil, vardenafil, tadalafil) demonstrated no increase in MI or death rates in men who received these agents as part of either double-blind, placebo-controlled trials or open-label studies, compared with expected rates.14, 15, 16, 17 Patients with known coronary artery disease or heart failure receiving PDE-5 inhibitors did not exhibit worsening ischemia, coronary vasoconstriction, or

Emergency Department Considerations: Management of Cardiovascular Symptoms or Priapism in PDE-5-Inhibited Patients

Specific recommendations for patients presenting to the emergency department with acute cardiovascular symptoms or priapism were considered. Contacts between emergency department staff members and patients presenting with cardiovascular symptoms afford 2 important opportunities for the management of patients with ED: (1) to avoid potentially lethal co-administration of PDE-5 inhibitors and nitrates and (2) to identify patients at high risk for acute MI and death. Accordingly, emergency

Future Applications: Role of PDE-5 Inhibition in Cardiovascular Disease

PDE-5 inhibitors are currently approved by the Food and Drug Administration for treating ED. However, this class of drugs may have potential benefits for endothelial or cardiac function. Sildenafil was shown to decrease pulmonary artery pressures, improve cardiac output, and reduce symptoms in patients with pulmonary hypertension.34, 35 It has been approved by the FDA for the treatment of pulmonary arterial hypertension (WHO Group I) to improve exercise ability. In preliminary studies,

Non-PDE-5 Inhibitor ED Therapies and the Cardiovascular System

Other pharmacologic agents besides PDE-5 inhibitors are used to treat ED and may affect the cardiovascular system. Yohimbine, an α-2 receptor blocker, has been advocated for more than a century as a treatment for ED.41 Results to date with yohimbine have been inconsistent, however, and adverse cardiovascular events have been observed in some studies. l-Arginine is the precursor of nitric oxide. It has been evaluated in men with minimal or mild ED, for which a benefit over placebo was recorded

Hypogonadism and Testosterone Therapy

The role of testosterone therapy for hypogonadism is expanding, in part because of increasing awareness of ED and recognition of hypogonadism as a co-morbid condition associated with type 2 diabetes, the metabolic syndrome, and other chronic systemic illnesses.45 The use of testosterone as an adjunctive therapy to PDE-5 inhibitors for the treatment of ED and hypogonadism has resulted in successful outcomes in patients in whom PDE-5 inhibitor therapy alone has failed.46 Published research

Primary Care Management, Disease Prevention, and Lifestyle Modification: Toward a Patient-Centered Approach

For generalists and specialists alike, the management of patients with ED and concomitant cardiovascular disease or risk factors presents unique challenges and opportunities. Current guidelines emphasize the need for a complete medical history and physical examination, in addition to laboratory testing, as needed49 (Figure 2). Co-morbid cardiovascular diseases or significant risk factors, in particular, including hypertension, diabetes, and dyslipidemia, are key areas to investigate in the

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    The Second Princeton Consensus Conference was supported by unrestricted educational grants from Pfizer Inc., New York, New York; Lilly/ICOS LLC, Bothell, Washington; Vivus, Palo Alto, California; Solvay, Marietta, Georgia; and Sanofi-Synthelabo, Bridgewater, New Jersey.

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