Viagra: Safe or sorry?

Opposing viewpoints on the drug’s safety

Viagra has been a boon to millions of men with erectile dysfunction, including men with diabetes, since it was introduced in March 1998.

But disturbing new information recently made public by a cardiologist at Cedars-Sinai Medical Center in Los Angeles indicates there may be a greater risk of death and adverse cardiovascular events associated with sildenafil (Viagra) than was originally believed.

This news is of particular concern for clinicians treating men with diabetes. The drug already is considered a high risk for heart disease.

However, another recent study from the Univer-sity of California Los Angeles (UCLA) says that sildenafil caused no undue cardiovascular risks for men with diabetes who took it, and other studies have shown it is effective for about 60% of them.

Drug not for patients taking nitrites

Shortly after Viagra was introduced to the market, physicians were warned not to prescribe Viagra for patients using nitrate heart drugs, patients who had cardiovascular conditions for whom sexual activity was inadvisable, and patients whose heart disease could be aggravated by sudden drops in blood pressure.

Searching the records of the U.S. Food and Drug Administration (FDA) under a Freedom of Information request, Cedars-Sinai critical care cardiologist Sanjay Kaul, MD, found reports of 522 deaths in men taking sildenafil in the first year the drug was on the market. Approximately 10% of those deaths occurred in men with diabetes, Kaul says.

In addition, Kaul found 1,473 major adverse events in the FDA database related to sildenafil. He reported his findings at the American College of Cardiology scientific sessions in March.

"Viagra is an effective treatment for erectile dysfunction," says Kaul in urging wider clinical trials on Viagra. "But not enough is known about its dangers even though it is so commonly prescribed and so widely used."

Kaul says that premarket clinical trials on Viagra had fewer than 10% of the subjects with cardiovascular disease and none with unstable cardiovascular disease. Men who experienced any of the following conditions 16 months before the trial began were excluded: angina, MI, stroke, history of high or low blood pressure, and congestive heart failure.

Kaul notes that the Federal Aviation Admini-stration has prohibited airline pilots from using Viagra six hours before a flight because of the potential for fainting due to sudden drops in blood pressure and the visual disturbances some men have experienced.

"We present this to make a plea both to the company and the FDA to take these adverse events seriously. We need clinical trials in high-risk people," says Kaul.

He says he is not yet ready to call for the withdrawal of Viagra from the market, but he notes that other drugs have been withdrawn with far fewer deaths associated with their use, most notably Rezulin, a thiazolidinedione used to help control insulin resistance. Rezulin was withdrawn in March after 61 liver failure deaths were associated with its use.

"Viagra is a bit of a sacred cow because of what it does," says Kaul, comparing the drug’s emotional impact on its users to the ill-fated weight-loss drug Redux used by millions of women.

Viagra’s manufacturer, Pfizer Inc. reports 17 million prescriptions have been written for 6 million men and 130 million blue diamond-shaped tablets dispensed. Viagra retails for about $10 per pill.

The message for now is one of caution, says Kaul: "We must assess patients very carefully before we prescribe this medication, but I know many patients will go straight to the Internet and get it if their doctors won’t prescribe it."

New York City-based Pfizer did not respond to requests to discuss Kaul’s findings. The FDA issued a routine statement that it is closely monitoring and evaluating adverse event reports as it does with all drugs.

The other side of the coin

Stanley Korenman, MD, professor of medicine at UCLA, agrees that more study of Viagra’s effects is needed, but as author of a study of 252 men with diabetes using Viagra, Korenman falls firmly in the supportive camp.

In a paper presented to the Endocrine Society last year, Korenman found that men (average age 57) with diabetes who experienced erectile dysfunction for six months or more had significant improvement in the condition when they took 100 mg doses of Viagra.

However, other research shows Viagra is safe and well-tolerated by men with diabetes and is especially helpful in men who have few diabetic complications.

He is critical of Kaul’s analysis of the FDA data because there is no name or contact for persons reporting those events and "there is no way to know if the data are correct or to follow up on an event," Korenman says.

He also explains that cardiovascular disease becomes more common as a person ages, so deaths from cardiovascular events in men taking Viagra may be coincidental. He suggests the deaths may have occurred with or without Viagra: "There have been a few hundred deaths among millions taking the drug, while 300,000 men die of heart disease every year."

Korenman’s study showed Viagra is most effective in men with diabetes who have no complications or only one comorbidity and best given in 100 mg doses.

However, Korenman is cautious about screening his patients before he prescribes Viagra.

He is very strict about any patient using nitrates. "Oh, no, if they are even carrying nitrates around and even if they say they don’t use them, I won’t prescribe Viagra," says Korenman.

"I don’t treat people with congestive heart failure, cardiomyopathy or liver cirrhosis and edema with Viagra because a reduction in blood pressure for these people could be a catastrophe," he says. "I’d give them a vacuum pump instead."

Korenman says Viagra is a first line of treatment in any man with diabetes for whom it is not contraindicated. "This is another motivation for men with diabetes to really work at their control," he says. "It does such a wonderful job of bringing people back to life."

Yet there’s a classic case of male-female priorities in dealing with a sensitive issue like erectile dysfunction, says Korenman. "Many women tell me they would rather have a living husband than a dead sexual partner," he says.

[Contact Sanjay Kaul at (310) 423-4876 and Stanley Korenman at (310) 794-1816.]