(Fig. 6)
(Fig. 7)
(Fig. 8)
(Fig. 9)
Viagra or Sildenafil citrate is the product that was described in the November, 1997, Newsweek cover story. This pill has had very significant success. (Fig. 7) Viagra’s mechanism of action is blocking the effects of an enzyme system called 5-phosphodiestrase (PDE-5) which breaks down c-GMP. This results in the accumulation of neurotransmitters secreted by nerve endings at the time of sexual stimulation and these chemicals bathe the erectile tissue resulting in muscle relaxation and subsequent erection.
Viagra was carefully studied by Pfizer. In clinical trials included over 3,000 patients, age 17 to 87. All 21 patient studies showed a significant improvement in erectile dysfunction compared to placebo. It also demonstrated that appropriately applied, Viagra is safe. However, Viagra is contraindicated in patients using nitrates. It should not be used in those who need nitrates in any form. The use of Viagra also has side effects. The most frequent are headache, flushing, indigestion and visual abnormalities such as light sensitivity. Viagra is 4,000 times more effective on PDE-5 than on PDE-3. This is very important because PDE-3 controls heart muscle contractility. Since Viagra’s introduction there has been a concern for safety when it is used in patients with recognized cardiovascular disease. Pfizer has done a comprehensive assessment of Viagra in the post-marketing group of patients who use the drug. This was summarized in December, 1998. (Fig. 8)
The conclusions are that Viagra is clearly indicated for treatment of erectile dysfunction. Over 200,000 physicians have prescribed it. Six million prescriptions have been written, 3 million patients have received these prescriptions and 50 million tablets have been dispensed. This post marketing review concludes that the experience is consistent with the clinical trials and there is no evidence to suggest that Viagra increases the cardiovascular risk that is known to be inherent in sexual activity in men age 55 or older. (Fig. 9) In the 55 and older group nearly 80 % have other organic problems including hypertension, heart disease, diabetes, or they need to take medications known to cause erectile dysfunction. These patients clearly have a three times greater risk of heart attack or stroke during periods of intense activity. The logical conclusion is that the combination of these underlying diseases and sexual activity create and increase risk of an adverse cardiovascular event.
Before prescribing Viagra, physicians must document the cardiovascular history, the medications needed for its treatment or management of other health problems. They should also discuss the potential for an adverse event occurring in patients undergoing the stress of sexual activity, particularly those patients with pre-existing cardiovascular disease.
Through the seven months of sales of Viagra ending in October, 1998, 6 million prescriptions have been filled in the United States. The FDA reported in November, 1998, that there were 130 deaths in the U.S. among men who had received a Viagra prescription. Analysis of the post-marketing data demonstrates that this death rate is not outside the range expected for patients who are in the general risk group of those having erectile dysfunction, the patient group over the age of 55. (Fig. 9) It is interesting to look at the clinical trials because in a similar group that series, cardiovascular adverse events were actually higher in the placebo arm of the study rather than those patients who were on Viagra. Nevertheless, Viagra should be prescribed with great caution in patients who have suffered myocardial infarction, stroke or threatening arrthymias within the past 6 months or in patients with resting blood pressure below 90/50 or elevated blood pressure above 170/110. Patients who have had cardiac failure, recurring coronary artery disease causing unstable angina should probably not receive Viagra at all.
In summary, there is a significant degree of cardiac risk associated with sexual activity. Physicians treating erectile dysfunction should consider the overall cardiovascular status before deciding on any treatment strategy. When all circumstances are considered and it is recognized that patients in the age group where erectile dysfunction occurs may have other significant cardiovascular problems or other general health issues, it may well be appropriate as Dr. Bernie Silbergeld, author of "The New Male Sexuality" has stated "instead of reaching for a pill, maybe some of these couples would be happier learning to cuddle their way into the later years".
References:
Korenman, S: New insights into erectile dysfunction : a practical approach. Am J. Med 105, August, 1998, 135-144.
Burnett, A: Erectile dysfunction : a practical approach for primary care. Geriatrics 53:2, February, 1998, 34-48.
Mobley, D and Baum, N: When patients request the impotence pill. Postgraduate Med 104:2, August, 1998, 55-66.
Pfizer, Inc: Postmarketing safety of sildenafil citrate (Viagra). December 10, 1998, http:ll www.fda.gov/bbs/topics ANSWERS/ ANS 00926. html
Silbergeld, B: The New Male Sexuality. Little, Brown ed February 1978; December, 1978, Bantam ed.