Major New Study Finds Long-acting Calcium Channel Blockers Inferior to Other Antihypertensive Drugs

August 29, 2000

Up to 85,000 unnecessary heart attacks and cases of heart failure may occur worldwide every year among the estimated 28 million users of longer-acting calcium channel blockers (CCBs), a class of drugs used to treat high blood pressure, according to the results of a study reported today at the European Society of Cardiology meeting in Amsterdam.

The combined analysis of nine randomized clinical trials, with a total of more than 27,000 patients, showed that the longer-acting CCBs are inferior to other proven and less expensive drugs in preventing the cardiovascular complications of hypertension.

The study was conducted at Wake Forest University School of Medicine in Winston-Salem, the University of Washington-Seattle, and Albert Einstein College of Medicine, Bronx, New York.

"The results are remarkably consistent across the trials," said Marco Pahor, M.D., professor of internal medicine at Wake Forest and the study''s lead researcher. "In the CCB-treated patients, the risk of a heart attack was 27 percent higher, the risk of heart failure was 26 percent higher and the risk of any major cardiovascular event was 11 percent higher. There was no difference in stroke or total mortality; and there was no evidence of differences among the CCBs tested."

The results add to a growing body of evidence that antihypertensive drugs, despite having equal effect on blood pressure, may vary in their ability to prevent heart attacks and congestive heart failure, said Curt D. Furberg, M.D., Ph.D., professor of public health sciences at Wake Forest University School of Medicine and a co-researcher of the study.

"The overuse of these less effective CCBs - which can cost 10 to 15 times more than diuretics - is a major avoidable clinical problem that requires immediate attention," Furberg told the cardiology society meeting in Amsterdam.

The study examined the results of nine long-term trials involving 27,743 patients, with a total of about 120,000 person-years of treatment. These trials compared a longer-acting CCB as initial treatment against an alternative antihypertensive drug -- diuretic, beta-blocker and ACE (angiotensin-converting enzyme) inhibitor. The blood pressure change was almost identical for the CCB and the non-CCB treatment groups.

"Blood pressure reduction, by itself, contributes substantially to protecting the heart and preventing blood vessel disease, which is the goal of antihypertensive therapy," said Michael H. Alderman, M.D., professor of epidemiology and social medicine at Albert Einstein College of Medicine and one of the researchers in the study. "But many types of drugs can lower blood pressure, and because drugs lower blood pressure by different means, it is not surprising that these agents would have differing effects on the occurrence of heart attacks, strokes and congestive heart failure."

A controversy over CCBs began in 1995, when a series of scientific articles showed that short-acting CCBs might be harmful. Those studies were criticized because many of them were observational. The large, long-term definitive trials testing the hypothetical benefits from CCB therapy had not yet been conducted.

That earlier data led the researchers to conduct the "meta-analysis" of all the clinical trials that have compared CCBs to other antihypertensive drugs. Combined, there were more than 700 cases of heart failure, more than 1,000 heart attacks, more than 1,200 strokes, more than 2,300 deaths and more than 3,300 combined cardiovascular events.

"Because of the large size and rigorous methodology of the individual trials these combined findings here have a high degree of reliability," said Alderman. "They provide valuable new evidence to guide physicians in selecting drugs to maximize cardioprotection in hypertensive patients."

Bruce M. Psaty, M.D., Ph.D., professor of medicine, epidemiology and health services at the University of Washington and one of the study''s researchers, said that the findings draw attention to the need for large, long-term trials to evaluate the health benefits of drugs used to prevent the complications of hypertension.

"The current FDA requirements for the approval of antihypertensive drugs do not provide the kind of information needed to identify the optimal treatment or strategy of treatment for high blood pressure," said Psaty.

He said the message patients should take from the research is to consult their doctors.

"In all instances, patients should consult their physicians about any potential changes in their antihypertensive therapy," said Psaty. "If patients are not taking a proven therapy such as low-dose diuretics, it is reasonable for them to ask their physicians, ''Why not?''"

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