Federal health officials warned yesterday that a drug prescribed to treat high blood pressure and heart disease should be used "with great caution, if at all," and that the safety of related drugs taken by millions of Americans was unclear.
The warning from the National Heart, Lung and Blood Institute applied specifically to large doses of the short-acting form of nifedipine, which is marketed as Procardia by Pfizer Inc. and as Adalat by Bayer Co.
Nifedipine is one of 10 drugs called calcium channel blockers that are taken to control blood pressure and relieve pains from angina.
As a class, the drugs are the most widely prescribed in the United States, with 87.3 million prescriptions written last year for an estimated 6 million people. More than 2 million of the prescriptions were for the short-acting form of nifedipine.
The heart institute, a unit of the National Institutes of Health in Bethesda, stopped short of extending the warning to all calcium channel blockers.
The institute said it "is unclear" whether the warning should be applied to all of the drugs because some studies indicated a danger, others did not; none were definitive, and insufficient data existed about the drugs' long-term safety.
The warning followed the recommendations of a panel of experts appointed by the heart institute to review scientific evidence, including a number of new studies, to assess the safety of calcium channel blockers.
The warning, which is not binding on doctors, is likely to leave many patients and doctors confused because experts are sharply divided about the safety of the drugs.
For instance, the American College of Cardiology, also in Bethesda, said that it stood by an earlier statement that "patients taking calcium channel blocking agents should assume that these drugs are not dangerous to them" but should discuss the issue with their doctors.
Federal health officials and leading cardiology groups advised patients not to stop taking calcium channel blockers without consulting their doctors. They said that uncertainties about the choice of drugs should not interfere with efforts to control high blood pressure, which if untreated could lead to complications like strokes and heart attacks. Alternative drugs are available.
In a new study on nifedipine that contains unusually strong language for a scientific report, Dr. Curt D. Furberg and his co-authors said their findings were "alarming."
The study is being published today in Circulation, a leading medical journal published by the American Heart Association in Dallas.
"Regulatory agencies ought to consider whether moderate to high doses of nifedipine capsules should be excluded from the approved" indications for their use, Dr. Furberg's team wrote.
Dr. Robert Temple, a top official of the Food and Drug Administration, said Dr. Furberg's study provided "credible data, and we need to look at it closely, and we will."
"There may need to be a change in labeling for that preparation," said Dr. Temple, who participated on the panel that issued the warning about short-acting nifedipine.
The study measured 16 earlier clinical trials involving 8,350 patients who had had heart attacks and who took nifedipine.
The analysis showed that high doses of nifedipine nearly tripled the death rate. Among those who took high amounts (80 milligrams a day or more) of short-acting nifedipine, the average risk of death during the study was 6 per 100 patients as compared with a death rate of 2 percent to 3 percent among those who took either a dummy medication or no drug.
The analysis showed little or no increase in death among patients who received low amounts (50 milligrams a day or less) and a slight increase among those who received 60 milligrams a day.
Because the meta-analysis focused on patients who had already had heart attacks, experts disagreed over how applicable it was to patients with other conditions.
In a news release, Pfizer did not address the warning, but it called Dr. Furberg's study "a flawed rehash of old data." The company noted that its newer, long-acting formulations, Norvasc and Procardia XL, were not included in the study and said that the reports "may unnecessarily provoke patients' concern" about their drug treatment.