PubMed2003
BACKGROUND: Erectile dysfunction (ED) is defined as the inability to attain and/or maintain penile erection sufficient for satisfactory sexual performance. ED may also be an early sign of cardiovascular disease. The main risk factors for coronary heart disease (high LDL, smoking, hypertension, diabetes) and ED are the same. ED after the diagnosis of coronary artery disease or myocardial infarction is also common. CARDIOVASCULAR EFFECTS AND RISK OF SEXUAL ACTIVITY: Cardiac and metabolic expenditures during sexual intercourse will vary depending on the type of sexual activity. When oxygen uptake was measured in men, an average metabolic expenditure during stimulation and orgasm of 2.5 metabolic equivalents (METs) was found for woman-on-top coitus, and of 3.3 METs for man-on-top coitus (range 2.0-5.4 METs). However, coital death is rare, encompassing only 0.6% of all sudden death cases. A retrospective case-crossover study has shown that although sexual activity can trigger the onset of myocardial infarction, the relative risk in the 2 h after sexual activity was low (2.5; 95% confidence interval [CI] 1.7-3.7). Sexual activity was a likely contributor to the onset of myocardial infarction only 0.9% of the time. Regular exercise appears to prevent triggering. It has to be cautioned that these reassuring data should not be extrapolated to patients taking sildenafil, if they perform at higher cardiac and metabolic expenditures during coitus. The hemodynamic changes associated with sexual activity may be far greater with an unfamiliar partner, in unfamiliar settings, and after excessive eating and drinking. The Princeton Consensus Table for estimation of cardiovascular risk during sexual intercourse gives a first orientation regarding the question which patients can perform sex safely and which subgroup needs further diagnosis and treatment. PHOSPHODIESTERASE-5 INHIBITORS FOR ED TREATMENT: The introduction of sildenafil has been a valuable contribution to the treatment of ED. Sildenafil acts as a selective inhibitor of cyclic guanosine monophosphate-(cGMP-)specific phosphodiesterase type 5 (PDE 5), resulting in smooth muscle relaxation, vasodilation, and enhanced penile erection. Reported cardiovascular side effects in healthy males are headache, flushing, and < 10% decreases in systolic and diastolic blood pressures. Significant hypotension can be found in patients who are concurrently taking nitrates. On the basis of the pharmacokinetic profile of sildenafil, the co-administration of a nitrate within the first 24 h is likely to produce a severe, potentially lifethreatening hypotensive response and is therefore contraindicated. The risk of precipitating a cardiotoxic, hypotensive, or hemorrhagic event secondary to combining sildenafil (a PDE 5 inhibitor) with specific PDE 3 inhibitors such as milrinone and enoximone or with nonspecific PDE inhibitors such as theophylline and pentoxifylline is unlikely. Sildenafil is predominantly metabolized by both the P450 2C9 pathway and the P450 3A4 pathway. Thus, potent inhibitors of the P450 3A4 pathway may increase the plasma concentrations of sildenafil, like cimetidine, erythromycin, digitoxin, and CSE inhibitors (simvastatin, atorvastatin, etc.). A creatinine clearance < 30 ml/min also increases plasma levels of sildenafil. SAFETY PROFILE OF SILDENAFIL: Sildenafil is safe in healthy subjects. In a postmarketing study on 6,527 males, no increase of cardiovascular events was found. However, in older males with coronary heart disease, the risk of sildenafil and the risk of physical exercise during sexual intercourse contribute both to fatal outcomes. Of 69 cases reported to the FDA, 46 patients might have had a cardiovascular event, and in twelve a possible interaction with nitrate use has been reported. Sildenafil is absolutely contraindicated in patients taking long-acting nitrates, those with severe aortic stenosis, and patients with hypertrophic obstructive cardiomyopathy (HOCM). No nitrates should be used within 24 h of sildenafil use. Caution is necessary in patients with a combination of antihypertensive medications, and in patients with cardiac insufficiency. A "pre-Viagra" treadmill test to assess for the presence of stress-induced ischemia can be helpful for both the patient and the physician. If the patient can achieve > or = 5 METs without demonstrating ischemia, the risk of ischemia during coitus is low. MANAGEMENT OF SEVERE ADVERSE EVENTS: If severe hypotension occurs, aggressive fluid resuscitation is the first step, followed by administration of vasoactive drugs and, if necessary, by intraaortic balloon counterpulsation. If unstable angina or myocardial infarctions occurs after the use of sildenafil, the patient is treated according to the guidelines, but without nitrates. CONCLUSION: Sexual activity is a cornerstone of quality of life. However, giving the incidence of "occult" cardiovascular disease in patients with ED and the indications and contraindications of PDE 5 inhibitors in patients with cardiovascular diseases, all patients with ED must be evaluated by a cardiovascular specialist.