The use of certain types of calcium channel blocking drugs for treating hypertension in older people is being called into question by scientists at the National Institute on Aging (NIA). Their new analysis is among the first to examine the risks of various antihypertensive drugs in an older population, and confirms reports earlier this year expressing particular concern about the short-acting form of nifedipine, a calcium channel blocker. According to the study, over a five-year period, older people taking short-acting nifedipine had double the risk of death of those taking a different medication.
The findings are reported in the November 1995 issue of the Journal of the American Geriatrics Society in a study by NIA exchange scientist Marco Pahor, M.D., Jack Guralnik, M.D., Ph.D., and other investigators at the NIA.
Pahor and Guralnik's paper is the third in a series of research findings that recently prompted the National Heart, Lung, and Blood Institute (NHLBI) to issue a statement urging "great caution" in prescribing short-acting nifedipine, especially at higher doses. The NIA and the NHLBI, both parts of the National Institutes of Health, suggest that doctors and patients may need to consider drug selection in light of the new findings.
However, NIA Director Richard J. Hodes, M.D., stressed, "The current controversy about short-acting nifedipine should not stop doctors from treating patients for hypertension with diuretics, beta blockers, and, as necessary, long-acting calcium channel blockers, or other approved medications. It is important that patients and doctors communicate about treatment for hypertension, and that patients not stop taking their medications without medical supervision." Said Hodes, "These studies should inform doctors and patients, not scare them."
The NIA research is based on studies of three communities in the NIA's Established Populations for Epidemiologic Studies of the Elderly (EPESE). The effects of different medications for hypertension were analyzed for 906 study participants, who were followed from 1988 through 1992. Scientists examined death from any cause, taking into account several factors including age, gender, smoking, cholesterol, and diseases such as congestive heart failure, coronary heart disease, diabetes, chronic pulmonary disease, and cancer. They then compared the mortality risk of people taking calcium channel blockers with those taking beta blockers to control hypertension.
The results showed that hypertensive older people who took short-acting nifedipine were nearly twice as likely to die within five years as those using beta blocker therapy. In addition, among people taking short-acting nifedipine, dosage was associated with risk of death: the higher the dose, the greater the mortality risk. The NIA findings showed little or no significant risk of increased mortality associated with the use of other calcium channel blockers, including verapamil and diltiazem.
The study was not able to draw any definitive conclusions about the long-acting form of nifedipine, which is the most common form of the drug prescribed today. The long-acting forms have been in use for a shorter period of time, and were not a part of this study.
Several large clinical trials are underway to further evaluate the safety and effectiveness of long-acting calcium channel blockers and other types of antihypertensive medications. Researchers are now recruiting participants for the NHLBI-sponsored ALLHAT (Antihypertensive and Lipid Lowering Treatments to Prevent Heart Attack Trial), which will, among other things, compare the effects of a diuretic, an ace inhibitor, a long-acting calcium channel blocker, and an alpha blocker in older people. Scientists hope that results of such clinical trials will yield more reliable guidelines as to the most appropriate use of all types of calcium channel blockers.
Why short-acting nifedipine is linked to an increase in mortality is unclear at this point. Pahor and Guralnik suggest that nifedipine can cause excessively low blood pressure, resulting in problems from overtreatment if people continue taking the drug. Nifedipine also is known to increase heart rate and decrease the force with which the heart pumps, which could lead to heart failure. Long-acting forms of the drug need to be taken only once a day, while the short-acting form must be taken several times a day and may cause detrimental changes in heart function, the scientists theorize.
Pahor and Guralnik caution that the NIA analysis is an epidemiological, observational study and that more definitive conclusions about the use of these drugs and their effectiveness will come from clinical trials. In the meantime, the epidemiological study provides guidance for those who are concerned about the use of these drugs, the authors say.
Hypertension, defined as blood pressure at or above 90 millimeters of mercury for the lower or diastolic reading and/or at or above 140 millimeters of mercury for the higher or systolic reading, is common among older people and becomes more common with increasing age. Up to 50 million Americans have high blood pressure and close to 50 percent of those people are over 65. People with hypertension are at increased risk for heart attack and stroke.
Treatment with a variety of drugs, in addition to changes in diet and exercise, quitting smoking, and other lifestyle changes, have markedly decreased illness and prolonged survival for the elderly with hypertension. Nearly 60 million prescriptions are filled each year in the U.S. alone for antihypertensives, with diuretics, beta blockers, and calcium channel blockers the three most common categories prescribed. Calcium channel blockers were first introduced in 1980. In May 1995, a study supported by the NIA and the American Heart Association (AHA), reported in the AHA journal Hypertension, noted that doctors were prescribing the new and significantly more expensive drugs such as calcium channel blockers without evidence that they are any more effective than older and more established diuretics.
The NHLBI and the NIA are two of the seventeen institutes which comprise the NIH. NIA leads the federal effort supporting basic, clinical, epidemiological, and social research on aging and the special needs of older people.