Number 28, 2005
Sex and the Heart

Managing sexual dysfunction in the cardiac patient

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Adolph M. Hutter Jr
Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
Correspondence: Dr Adolph M. Hutter Jr, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Exploring the issue with the patient
Patients with cardiovascular disease, particularly coronary artery disease, are more likely to have erectile dysfunction, and vice versa. Indeed, the risk factors (hypertension, diabetes, hyperlipidemia, smoking) for one problem are also the risk factors for the other [1–3]. Endothelial dysfunction is seen in both coronary artery disease (CAD) and erectile dysfunction [4]. Consequently, when a physician sees a patient with erectile dysfunction, exploration for the presence of these risk factors, and the possible presence of CAD, should be undertaken. Similarly, the physician seeing the patient with CAD, congestive heart failure, diabetes, hypertension, or hyperlipidemia should inquire about the adequacy of sexual function. Erectile dysfunction is a common problem, but one that is infrequently raised by either the patient or the physician. Since we now have so many advances that have made CAD a chronic disease that a patient can live with rather than die of, quality of life becomes important. Sexual activity is an important aspect of a good quality of life for most patients.
The availability of oral phosphodiesterase type-5 (PDE-5) inhibitors (sildenafil, tadalafil, and vardenafil) has opened a wide window of opportunity to help men with erectile dysfunction, including those with cardiovascular disease. It is very helpful to involve the partner in these discussions. This not only gives a more accurate picture of any problems in the area of sexual relations, but also provides reassurance to the partner as the evaluation process proceeds.

Safety of PDE-5 inhibitors
The PDE-5 inhibitors have now been used in thousands of patients. A number of drug–placebo and open-label studies have shown the overall safety of sildenafil and tadalafil in patients with cardiovascular disease. They have been shown not to increase the incidence of myocardial infarction or cardiovascular death compared with placebo treatment [5–10].

Coronary artery disease
Sildenafil has been shown to have no deleterious effects on exercise in patients with stable CAD. Arruda-Olson et al [11] performed a randomized placebo-controlled trial with sildenafil in patients with CAD and positive stress imaging tests. Compared with placebo, sildenafil decreased the resting systolic and diastolic blood pressures slightly, with no difference in the resting heart rate. There was no difference in exercise capacity, blood pressure, or heart rate. There was also no difference in symptoms with exercise, positive electrocardiogram changes, exercise-induced wall motion abnormalities, or rest or exercise ejection fraction. Fox et al [12] showed that sildenafil did not adversely affect the exercise performance of patients with stable angina. Compared with placebo, there was no difference in time to 1 mm ST-segment depression or total exercise time. Sildenafil actually prolonged the time to angina. Thadani et al [13] studied men with reproducible angina on exercise and showed that vardenafil 10 mg did not change the total exercise time or time to angina compared with placebo and actually increased the time to ischemic ST-segment changes. In a small number of patients with stable CAD, Patterson et al [14] showed that tadalafil 10 mg caused no difference in total exercise time or time to ischemia compared with placebo. Thus all three agents have been shown to have no deleterious effects on the exercise performance of men with stable CAD and angina, and even perhaps to have some benefit.

Congestive heart failure
The American College of Cardiology and American Heart Association (ACC/AHA) published an Expert Consensus Report on the safety of sildenafil in patients with cardiovascular disease in 1999. Concerns were raised about patients with congestive heart failure and patients receiving several antihypertensive agents [15].
Sildenafil has subsequently been shown to be safe with regard to the exercise performance of patients with congestive heart failure. Bocchi et al [16] studied 23 patients with this condition. Compared with placebo, sildenafil reduced the resting heart rate and systolic and diastolic blood pressures, but actually increased the exercise time, increased oxygen consumption, and attenuated the increment in heart rate with exercise. Lepore et al [17] studied sildenafil in patients with Class III heart failure and found that the drug increased work efficiency, peak oxygen consumption, exercise cardiac output, and stroke volume, while decreasing rest and exercise pulmonary vascular resistance and post capillary wedge pressure without a significant change in arterial blood pressure.

Hypertension
The PDE-5 inhibitors are mild vasodilators and may cause a small decrease in systolic and diastolic blood pressure, which is generally of little consequence. The ACC/AHA expert consensus report expressed caution about using these drugs in patients with hypotension and hypovolemia [15]. It was also stressed that all vasodilators should be used with caution in patients with aortic stenosis and left ventricular outflow obstruction. At the time of that report, concerns were raised about using these drugs in patients receiving several antihypertensive agents. However, a large number of studies have since shown that the PDE-5 inhibitors have little effect on the systolic blood pressure when used in the presence of a single or several antihypertensive agents [18].
If there is concern that the blood pressure may be too low to allow the safe use of a PDE-5, a simple trial of a low dose and a check of the blood pressure about 30 min later can allay that concern. If there is no decrease in blood pressure, the patient can then use that dose for the purpose of sexual intercourse, without concern to him or his partner. If he requires a higher dose for efficacy, a repeat check of the blood pressure after the higher dose can be performed to make sure that the higher dose does not induce hypotension.

Nitrates
Combining PDE-5 inhibitors with nitrates can result in a profound decrease in blood pressure that is unpredictable in the individual concerned. Although the average decrease in blood pressure may be modest, the decrease in an individual patient may be severe. This phenomenon can be evaluated by determining the number of “outliers” – that is, the number of individuals who have a minimum standing systolic blood pressure of less than 85 mm Hg – after the use of nitrates combined with the PDE-5 inhibitor, in comparison with placebo. Merely averaging the decrease in blood pressure will not detect these individual marked responses. Thus the use of PDE-5 inhibitors is absolutely contraindicated in patients receiving nitrates. Nitrates should be avoided for 24 h after the use of the shorter-acting sildenafil and vardenafil [15], and 48 h after the use of a longer-acting tadalafil [19].

Screening the cardiovascular patient before sexual activity
The Princeton Consensus Conference developed a risk stratification algorithm to determine the amount of cardiovascular risk associated with sexual activity in men with different degrees of cardiovascular disease [20]. These recommendations have recently been updated [21] (Figure 1).

Management of the patient with acute coronary syndrome after using a PDE-5 inhibitor
Patients who present with chest pain consistent with acute coronary syndrome or myocardial infarction and who have recently used a PDE-5 inhibitor should not receive nitrate therapy, which is absolutely contraindicated, but can receive all other appropriate therapy, including aspirin, heparin, thrombolytic agents, glycoprotein IIb/IIIa agents, β-blockers, and, if indicated, calcium channel blockers. It is important for the patient to tell the emergency personnel and for the emergency personnel to ask the patient about the possible use of a PDE-5 inhibitor, so that nitrate therapy is not given inadvertently.

Management of the hypotensive patient who received a combination of PDE-5 inhibitor and nitrates
The patient who presents with hypotension after a combination of PDE-5 inhibitor and nitrate therapy should be treated with volume resuscitation and, if necessary, an intravenous α-blocker such as phenylephrine, which will support the blood pressure by causing peripheral vasoconstriction without increasing cardiac work (contractility). If necessary, an intra-aortic counterpulsation balloon can be used to stabilize the systemic circulation [15].

Summary
The vast majority of patients with cardiovascular disease can safely use the PDE-5 inhibitors. We, as physicians, should inquire about erectile dysfunction in our patients with cardiovascular disease and, if it is present, explain that we have ways of helping them in this regard. A clinical evaluation, often including an exercise test, can quickly identify those patients who may safely resume sexual activity and use PDE-5 inhibitors.

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