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NHLBI Panel Reviews Safety of Calcium Channel Blockers

Statement Offers Guidance to Physicians

Embargoed for Release:
August 30, 1995

Short-acting nifedipine, a type of calcium channel blocker prescribed for hypertension and certain heart disorders, should be used with "great caution (if at all)," especially at higher doses, concludes the National Heart, Lung, and Blood Institute in a statement for health professionals. 

The statement is based on a review of the available scientific evidence on the safety of calcium channel blockers, including smaller clinical trials and several new studies. The review was conducted by an ad hoc panel on calcium channel blockers convened by the NHLBI in June 1995. Among the studies reviewed is a meta-analysis of 16 trials of nifedipine in patients with coronary heart disease, published in the September 1 issue of the American Heart Association's journal "Circulation." The meta-analysis, which pooled the results of the 16 studies, revealed an increase in deaths among patients taking nifedipine in doses of 80 mg. or greater. 

The recommendation concerning nifedipine was one of several contained in the NHLBI statement, which is intended to help guide physicians and other health professionals as they advise their patients about the safety of calcium channel blockers. 

"This statement is intended to provide a much-needed perspective on the safety and effectiveness of calcium channel blockers," said NHLBI Director Dr. Claude Lenfant. 

"It will help physicians counsel their patients, many of whom panicked when the results of a case control study of calcium channel blockers were misinterpreted," added Dr. Lenfant. 

The statement acknowledges that calcium channel blockers are effective in the relief of certain heart disorders such as angina pectoris and some arrhythmias and in the reduction of blood pressure. It cautions, however, that like most drugs, calcium channel blockers have multiple effects, so it is important to establish the risks as well as the major benefits. There are three sub-classes of calcium channel blockers. The following is a list of classes and examples of each: dihydropyridines (nifedipine), phenylalkylamines (verapamil), and benzothiazepines (diltiazem). These three "sub-classes" are chemically distinct and have some pharmacological differences. In addition, several calcium channel blockers have both short-acting (requiring several daily doses) and long-acting (once daily) forms. The NHLBI statement concludes: 

*The nifedipine finding cannot necessarily be generalized to any other calcium channel blocker including longer-acting dosage forms of nifedipine and short-acting formulations of other drugs such as diltiazem and verapamil. The latter two drugs were associated with an increased risk of heart attack in a University of Washington case-control study of hypertensive patients. However, diltiazem and verapamil were not associated with increased risk of death or heart attack in other studies, including well-designed clinical trials in heart attack patients, a group at high risk of recurrent heart attacks. 

*The results of large-scale randomized clinical trials, such as the ongoing Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), are essential to the ultimate resolution of the issues of safety and effectiveness. 

*Health professionals should review current treatment guidelines, including the fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V). According to JNC V, which is 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. 

*Current uncertainties about the choice of drugs for the treatment of hypertension should not interfere with efforts to achieve blood pressure control. It has already been proven that treating hypertension prevents stroke and heart attack. 

The complete text of the NHLBI statement will be available online ( or gopher:// Members of the press can call (301) 496-4236 for the statement.