How would you know if your medicine was putting you at risk for heart disease?
This might seem as simple as looking on the official labeling, but you might be surprised to learn that the Food and Drug Administration has a very hard time detecting drug-induced heart disease.
Vioxx was a classic case. This arthritis drug was promoted as less likely to cause serious digestive-tract complications compared with other pain relievers such as diclofenac, ibuprofen, meloxicam and naproxen.
It came as a great shock to doctors and patients alike in 2004 when Vioxx was linked to heart attacks and unceremoniously pulled off pharmacy shelves.
An FDA safety officer estimated that the drug might have been responsible for as many as 30,000 to 40,000 deaths during its five years on the market. It was later discovered that other popular pain relievers, including Celebrex, diclofenac and ibuprofen, also could raise the risk of heart problems.
When we asked a key FDA executive why the agency missed the iceberg that nearly sunk his organization, he replied that the FDA is not very good at catching common things such as heart attacks or strokes. It seems to be able to detect strange or rare complications such as liver failure, but "common" problems, such as heart attacks, frequently go undetected for years because the massive amount of data overwhelms the signal.
The diabetes drug Avandia posed a similar challenge. It was first marketed in 1999. In 2007, an article in the New England Journal of Medicine (June 14, 2007) revealed that the drug was associated with a significant (43 percent) increased risk of heart attack. Eventually, the FDA severely restricted the use of Avandia, and European regulators banned it outright.
Now another popular class of medicines is under scrutiny for potential heart problems. Proton-pump inhibitors (PPIs) are among the more widely prescribed drugs. These potent acid-suppressing medicines are used to ease everything from vague bellyaches to severe reflux disease and ulcers.
The drugs in question include esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix) and rabeprazole (Aciphex), among others. An article published in the American Heart Association's scientific journal, Circulation (online, July 3), has thrown a shadow on their safety.
The researchers found that PPIs may cause heart problems by reducing the flexibility of blood vessels. In addition to suppressing stomach acid, these agents reduce the body's production of nitric oxide in blood vessels. This natural compound keeps blood vessels supple and helps control blood pressure.
Perhaps this discovery helps explain the disquieting statistic that older people who leave the hospital on a PPI were 50 percent more likely to die during the following year than those who were not taking such medications (JAMA Internal Medicine, April 8). Major cardiovascular adverse events were more common among people on acid-suppressing drugs.
No one should stop a PPI suddenly, as this might trigger rebound hyperacidity and heartburn symptoms. But the data should prompt heart patients to ask their doctors to assess the benefits and risks of these medicines for them.
Joe Graedon is a pharmacologist. Teresa Graedon holds a doctorate in medical anthropology and is a