Calcium channel blockers not as effective as other drugs

December 06, 2000

WINSTON-SALEM, N.C. - Three standard drug treatments for high blood pressure - ACE inhibitors, beta blockers and diuretics - are significantly more effective than the newer, widely prescribed calcium channel blockers (CCBs) at preventing heart attacks and heart failure, report researchers in this week's The Lancet.

"In an analysis of more than 27,000 patients with high blood pressure, we found that those treated with CCBs had a 26 percent higher risk of heart attack and a 25 percent higher risk of heart failure than those treated with other drugs," said lead researcher Marco Pahor, M.D., professor of medicine at Wake Forest University Baptist Medical Center (WFUBMC).

The risk for all cardiovascular events combined - heart attacks, heart failure, stroke and death from heart disease - was 10 percent higher among those treated with CCBs.

"These results show that CCBs are less effective than the standard drugs used to treat high blood pressure," said Pahor. "They don't mean that CCBs are dangerous or that they are worse than receiving no treatment at all."

CCBs, also known as calcium antagonists, work by blocking calcium's role in contracting blood vessels and muscles. This action reduces the pressure of blood flow through the body. The Lancet article is the first published report of the study, which gained widespread attention when it was presented orally at the European Society of Cardiology meeting in Amsterdam in August. The results were also reported at the American Heart Association annual conference on Nov. 13.

"Prior to this analysis, there were only limited data to guide physicians about whether certain classes of drugs were more or less effective than others," said Pahor.

For the analysis, researchers from WFUBMC, the University of Washington-Seattle and Albert Einstein College of Medicine, Bronx, New York, combined the results of all clinical research trials published to date comparing CCBs with diuretics (water pills), beta-blockers or ACE (angiotensin converting enzyme) inhibitors. The analysis was able to provide results that were more statistically meaningful than the smaller studies could provide alone.

The researchers analyzed nine trials with a total of 27,743 participants who were followed for an average of four years. Of those, 12,699 were randomly assigned to take a CCB and 15,044 were randomly assigned to take a diuretic, beta-blocker or ACE inhibitor. Two of the trials were conducted in the United States, six in Europe and Israel and one in Japan.

The generic names for the CCBs used in the studies are amlodipine, felodipine, isradipine, nicardipine, nifedipine nisoldipine, diltizem and verapamil. The drugs they were compared with were: diuretics (amiloride, chlorthalidone, hydrochlorothiazide and trichlormethiazide), beta-blockers (atenolol, metoprolol and pindolol), and ACE inhibitors (enalapril, fosinopril and lisinopril).

Taken together, the nine clinical trials showed that CCBs were just as effective as the other drugs at lowering blood pressure. However, the CCBs were significantly less effective at preventing several major complications of hypertension: heart attacks, heart failure, and all cardiovascular events combined. No differences were found between the drugs in rate of strokes or other causes of death.

"These results are not surprising since it has been documented that in patients with heart failure, diuretics, ACE inhibitors and beta-blockers improve survival and reduce hospitalization - while CCBs don't," said Michael H. Alderman, M.D., professor of epidemiology and social medicine at Albert Einstein College of Medicine and a co-researcher of the study. "It has also been shown that beta blockers and ACE inhibitors prevent heart attacks in patients with coronary disease - while CCBs don't."

Alderman said the results point to the need to modify treatment guidelines for hypertension. "These data reinforce the view that use of CCBs should be limited to patients who do not tolerate, or who have failed on diuretics, beta-bockers and ACE inhibitors," he said. William B. Applegate, M.D., Ph.D., professor of internal medicine at WFUBMC and a co-researcher of the study, said that CCBs, which are still under patent, are 10 to 15 times more expensive than some of the proven generic drugs.

"Although many hypertensive patients will continue to require CCB therapy, if just half of the estimated 28 million users of CCBs worldwide were switched to low-dose diuretics, the costs savings (wholesale) might be as much as $11 billion a year worldwide," he said. The researchers said the message patients should take from the research is to consult their doctors.

"People who use CCBs shouldn't stop taking their medicines," said Bruce M. Psaty, M.D., Ph.D., professor of medicine, epidemiology and health services at the University of Washington and a co-researcher for the study. "They should consult their physicians, and if they are not taking a proven therapy such as low-dose diuretics, it is reasonable for them to ask their physicians, 'Why not?'"
This study received no external financial support.

Contacts: Wake Forest: Karen Richardson, Mark Wright or Bob Conn, (336) 716-4587.

Wake Forest Baptist Medical Center

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