August 22, 1995
A case-control study funded by the National Heart, Lung, and Blood Institute (NHLBI) and published in the August 23/30 issue of the "Journal of the American Medical Association" found that high blood pressure patients taking a calcium channel blocker may have a greater risk of heart attack than patients taking a diuretic or a beta blocker.
This study, conducted at the University of Washington, raises some concerns about the relative safety of calcium channel blockers that can only be conclusively answered in a large-scale, long-term randomized clinical trial. Such a trial is currently underway, but since the results are not yet available, the NHLBI is preparing a statement for physicians and other health professionals to help guide them as they advise their patients about the safety of calcium channel blockers. This statement will refine the Institute's position on calcium channel blockers. It will be based on a review conducted by an NHLBI-convened Ad Hoc Panel on Calcium Channel Blockers which met in June 1995. The panel reviewed the available scientific evidence on the safety of this class of drugs. The NHLBI statement will be completed and available to the public in early September.
In the University of Washington study, the investigators found a 60 percent higher "relative risk" of heart attack among the patients taking a calcium channel blocker compared to those taking a diuretic or a beta blocker. In addition, higher doses of calcium channel blockers were associated with greater risk. All of the calcium channel blockers in this study (nifedipine, diltiazem, and verapamil) were of the short-acting type requiring several daily doses. If this study's results are confirmed, the short-term risk of heart attack for an individual from calcium channel blockers would be low. For every 1000 high blood pressure patients treated with diuretics or beta blockers for one year, about 10 would be expected to have a heart attack within a year. The University of Washington study suggested that if the patients were taking calcium channel blockers, 16 rather than 10 might suffer a heart attack.
In a "case control" study such as this, scientists review medical records to identify patients or "cases" with a disease and then compare certain characteristics of these "cases" with a similar group of "control" patients. In the University of Washington study, scientists identified patients with hypertension at a health maintenance organization (HMO) and then used computerized pharmacy records to obtain information on the drugs being taken. Women with hypertension who had suffered heart attacks between 1986 and 1993 and men with hypertension who had heart attacks between 1989 and 1993 were compared with a "control" group of high blood pressure patients at the HMO who had not had heart attacks.
A case control study, although useful, cannot provide definitive information on the effectiveness and long-term safety of a class of drugs. Even with rigorous statistical procedures to make the cases and controls as similar as possible, there may be unknown and important differences which can account for the findings. For example, there may be differences related to the reasons why a specific drug was chosen. Only if the University of Washington's study's findings are confirmed in a long-term randomized clinical trial, will we know for sure that this class of drugs is tied to an increased risk of heart attack. The conclusions, even if validated in a clinical trial, would relate primarily to patients being treated for hypertension, because patients who had congestive heart failure or a prior heart attack were excluded from the study.
Hypertensive patients currently taking calcium channel blockers should not stop taking their medication and should discuss any concerns with their physicians. As always, the choice of drug for a particular patient is based on that individual's condition and an assessment of the drug's risks and benefits for that patient. Current treatment guidelines for physicians, which are included in the fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V), recommend diuretics and beta-blockers as preferred agents for high blood pressure. According to the JNC V, a document produced by the NHLBI's National High Blood Pressure Education Program, calcium channel blockers and other alternative drugs should be reserved for special situations or when diuretics and beta blockers have proved unacceptable or ineffective.
The JNC V noted an urgent need to study the long-term effectiveness and safety of the alternative drugs in reducing deaths and disability for cardiovascular disease. In pursuit of this goal, the NHLBI has initiated the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). The hypertension component of ALLHAT will compare the effects of a diuretic, an ACE inhibitor, a calcium channel blocker, and an alpha blocker in older hypertensive patients.
Related press release: NHLBI Panel Reviews Safety of Calcium Channel Blockers