The pharmaceutical preparation sildenafil citrate (Viagra) is being widely prescribed as a treatment for male erectile dysfunction, a common problem that in the United States affects between 10 and 30 million men. The introduction of sildenafil has been a valuable contribution to the treatment of erectile dysfunction, which is a relatively common occurrence in patients with cardiovascular disease. This article is written to appropriately caution and not to unduly alarm physicians in their use of sildenafil in patients with heart disease.
Reported cardiovascular side effects in the normal healthy population are typically minor and associated with vasodilatation (ie, headache, flushing, and small decreases in systolic and diastolic blood pressures). However, although their incidence is small, serious cardiovascular events, including significant hypotension, can occur in certain populations at risk. Most at risk are individuals who are concurrently taking organic nitrates. Organic nitrate preparations are commonly prescribed to manage the symptoms of angina pectoris. The coadministration of nitrates and Viagra significantly increases the risk of potentially life-threatening hypotension. Therefore, Viagra should not be prescribed to patients receiving any form of nitrate therapy.
Although definitive evidence is currently lacking, it is possible that a precipitous reduction in blood pressure with nitrate use may occur over the initial 24 hours after a dose of Viagra. Thus, for patients who experience an acute cardiac ischemic event and who have taken Viagra within the past 24 h, administration of nitrates should be avoided. In the event that nitrates are given, especially within this critical time interval, it is essential to have the capability to support the patient with fluid resuscitation and -adrenergic agonists if needed. In patients with recurring angina after Viagra use, other nonnitrate antianginal agents, such as -blockers, should be considered.
Other patients in whom the use of Viagra is potentially hazardous include those with active coronary ischemia; those with congestive heart failure and borderline low blood volume and low blood pressure status; those with complicated, multidrug, antihypertensive therapy regimens; and those taking medications that may affect the metabolic clearance of Viagra. With respect to patients following complicated multidrug, antihypertensive programs, the randomized studies included a large number of hypertensive patients. However, most patients were controlled with 1 antihypertensive agent, and only a small number were controlled with 3 antihypertensive agents. Until adequate studies are done in these subgroups of patients, sildenafil should be prescribed with caution.
Viagra acts as a selective inhibitor of cyclic GMP (cGMP)–specific phosphodiesterase type 5, resulting in smooth muscle relaxation, vasodilatation, and enhanced penile erection. Although the cardiovascular effects of sildenafil reported in available randomized, controlled clinical trials were relatively minor, heart disease patients represented only a small fraction of studied patients and patients with heart failure, patients with myocardial infarction or stroke within 6 months or patients with uncontrolled hypertension were not included in these studies. Thus, there are possible problems in the use of Viagra in these patients that have not been adequately studied.
Given the increasing reports of deaths in which the use of Viagra may be implicated, clinicians need to exercise caution when advising their patients with heart disease about taking this medication. Specific recommendations regarding sildenafil (Viagra) and the cardiac patient are summarized in the following Table.
Table 1. Summary Table of Clinical Recommendations
A. Use of Viagra clearly contraindicated
1. Concurrent use of nitrates (see )
B. Cardiovascular effects of Viagra may be potentially hazardous (use dependent on individual clinical assessment)
1. Patients with active coronary ischemia who are not taking nitrates (eg, positive exercise test for ischemia)
2. Patients with congestive heart failure and borderline low blood pressure and borderline low volume status
3. Patients on a complicated, multidrug, antihypertensive program
4. Patients taking drugs that can prolong the half-life of Viagra
Patients with erectile dysfunction are mostly over age 45 and are in general more likely to have risk factors predisposing them to cardiovascular disease, including myocardial infarction and stroke. The vast majority of patients in the clinical development program did not have known coronary disease or congestive heart failure, nor were hypertensive patients taking complicated, multidrug, antihypertensive medical regimens included in the program. Furthermore, 62% of the patients taking Viagra were within the 45- to 64-year-old age category, and only 23% were aged 65 years (Pfizer Inc, unpublished data). Although sildenafil is not presently indicated in women, the cautions referred to in this document should probably apply to both men and women, pending studies performed specifically in women.
Expert Consensus Documents, as noted in the preamble, are often written in circumstances in which the evidence base and experience with the technology or practice are limited. This is clearly the case with Viagra. The evidence base had significant limitations, and many important issues remain unresolved. Of special significance to the current report is the fact that the preapproval clinical trials of Viagra excluded certain high-risk groups of patients with significant cardiac disease (ie, patients with heart failure, patients with myocardial infarction or stroke within 6 months, or patients with uncontrolled hypertension) or patients with blood pressures of <90/50 or >170/100 mm Hg. More research needs to be done to assess the specific risks of Viagra use among these cardiovascular patients.
Expert Consensus Documents, as noted in the preamble, are often written in circumstances in which the evidence base and experience with the technology or practice are limited. This is clearly the case with Viagra. The evidence base had significant limitations, and many important issues remain unresolved. Of special significance to the current report is the fact that the preapproval clinical trials of Viagra excluded certain high-risk groups of patients with significant cardiac disease (ie, patients with heart failure, patients with myocardial infarction or stroke within 6 months, or patients with uncontrolled hypertension) or patients with blood pressures of <90/50 or >170/100 mm Hg. More research needs to be done to assess the specific risks of Viagra use among these cardiovascular patients.
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