WINSTON-SALEM, NC -- Calcium channel blockers and certain kinds of diuretics are associated with brain damage and memory loss, according to a report in today's Journal of the American Geriatrics Society -- another in a string of adverse findings about calcium channel blockers.
The latest results come from an analysis of participants with high blood pressure in the Cardiovascular Health Study (CHS), the largest study ever of the natural progression of heart disease and stroke in the elderly. The study, sponsored by the National Heart Lung and Blood Institute and begun in 1989, involves 5,888 residents of Forsyth County, N.C., Sacramento County, Calif, Washington County, Md., and Pittsburgh.
Curt D. Furberg, M.D., Ph.D., professor and chairman of the Department of Public Health Sciences at the Wake Forest University School of Medicine, called the results "a surprise finding." He said there was no reason to suspect that drugs that reduce high blood pressure would have such an adverse effect on the brain..
The new research looked at the 1,268 CHS participants who were being treated for high blood pressure by their personal physicians, but who had never had a stroke or reported a transient ischemic attack (a ministroke). Furberg, national chairman of CHS Steering Committee, said they found more evidence of brain damage and lower scores on a standard mental test in participants taking calcium channel blockers or so-called "loop" diuretics -- such as Lasix -- than in those using beta blockers, so-called ACE (angiotensin-converting enzyme) inhibitors -- such as Enalapril -- or thiazide diuretics.
The brain damage turned up under a Magnetic Resonance Imaging (MRI) examination as what doctors call "white matter hyperintensity", which has been associated with impaired memory. The standard mental test confirmed these findings of impaired memory.
Furberg said the results are part of a pattern of problems with calcium channel blockers that began to emerge with a report at an American Heart Association meeting in March 1995 by Bruce M. Psaty, M.D., Ph.D., of the University of Washington and Furberg.
"Now we have one article a month suggesting potential harm in the long-term use of calcium channel blockers," he said. The problems seem to arise in both long-acting and short-acting versions of the widely prescribed drugs, intended to treat high blood pressure and chest pain.
Calcium channel blockers have been implicated in problems with cardiovascular diseases, cancer, and unexplained stomach and intestinal bleeding. "Now we have suggestive evidence of effects on the brain, including brain damage and memory loss."
"In the global picture, this is yet another problem to be added to the list caused by calcium channel blockers," Furberg said. "The problem is that these and other newer drugs lower high blood pressure but were never properly evaluated for long-term safety."
He said dozens of reports from around the world document the safety concern again and again. Studies show that patients taking calcium channel blockers over a long period have an increase in heart attacks and strokes and in deaths from all causes.
But investigators also reported increased bleeding and increases in cancer in patients on calcium channel blockers.
In October, Furberg and the other CHS investigators reported calcium channel blockers doubled the risk of breast cancer in post-menopausal women. The number of cases was small, so the investigators warned, "These observed associations should be interpreted with great caution. However, the authors present these data so that other investigations may follow."
He said the adverse results show up in both clinical trials -- experimental tests of drugs -- and in observational studies, where investigators follow participants over a number of years, but do not interfere with treatment or otherwise intervene. CHS is an observational study.
And Furberg said the accumulating evidence of a safety problem has convinced even those initially critical of his results. Around the world, fewer and fewer patients are taking calcium channel blockers. "Physicians and patients are worried, and rightfully so."
In an editorial in the Nov. 15 issue of The Lancet, Furberg wrote, "In comparative trials, calcium channel blockers have never been shown to be better than, or even to be equal to standard therapy." In the editorial, Furberg challenged some of the conclusions in the just issued Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC VI) saying that its recommendations "are closer to consensus-based guidelines rather than evidence-based guidelines."
He added, "Clinicians who prefer evidence-based guidelines may have a mixed reaction to the lack of a simple and direct emphasis on treatments of proven safety and effectiveness."
Furberg said the debate is also having a major impact on what drug companies are now doing to document the safety of drugs that they wish to market.
The latest developments may also contain the explanation for why only some patients have problems with calcium channel blockers: the problems are occurring primarily in diabetics.
One study of diabetics with hypertension compared patients placed on ACE inhibitors with those placed on calcium channel blockers, and found that patients on the ACE inhibitor had half as many cardiovascular "events" as patients on calcium channel blockers.
Furberg said six additional studies, some published, some about to be published, are reporting similar findings, showing calcium channel blockers are particularly unsafe for diabetics.
Does that mean the drugs are safe for people without diabetes? "These drugs are untested in long-term trials and therefore, one can not conclude they are safe," Furberg said.
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Journal
Journal of the American Geriatrics Society