Calcium channel blocker study fails to sway critics
Older diabetics may benefit, but caution urged
Critics are pouring cold water on a recent Finnish study that says the use of calcium channel blockers in older diabetic patients produces dramatic reductions in myocardial infarction and stroke.
The study, published in the March 4 issue of the New England Journal of Medicine, concludes that nitrendipine-based antihypertensive therapy produced markedly improved results for diabetic patients with hypertension.
The study conducted by Finnish researchers as part of the Systolic Hypertension in Europe (Syst-Eur) trial found that over two years, the use of calcium channel blockers by 492 diabetic patients produced these results:
reduced systolic and diastolic pressure in diabetic patients by 10.3 and 4.5 mm Hg respectively;reduced overall mortality by 55%;
reduced mortality from cardiovascular disease by 76%;
reduced nonfatal stroke by 73%;
reduced all cardiac events by 83%.
Among non-diabetic patients, the study showed respective reductions of 26% and 38% for all cardiovascular events and all strokes.
A 1995 meta-analysis published in the journal Circulation showed that short-acting dihydropyridine calcium channel blockers seemed to provoke myocardial infarction (MI), as well as other data published in the intervening four years.
One of the authors of that original study was Bruce Psaty, PhD, MD, an internist and professor of medicine at the University of Washington in Seattle. Psaty is highly critical of the Finnish study’s methodology and the quality of the medical care available to the study’s subjects in Eastern Europe.
About half the patients in the Syst-Eur study were from Eastern Europe, which typically has "a lower quality of medical care," he says. "The CHF and stroke statistics in the study are typical of medical care in the U.S. in the 1960s. It looks like there were fewer events and higher numbers of fatalities, which suggests to me that either the investigators are missing mild events or the medical care system is missing them."
He points out that the Finnish study is "The one and only positive trial that has looked at calcium channel blockers."
He and a group of fellow researchers have written a letter to the New England Journal of Medicine disputing the findings.
Some of the issues Psaty pointed out were:
Trials are compared though placebo patients were not similar.The analysis was done through a posthoc subgroup analysis, rather than through a planned study, which "makes it difficult to know what it means."
The study was conducted on a drug that is not available in the United States (nitrendipine, a dihydropyridine calcium channel blocker).
Researchers say study is supported
The Finnish researchers, led by Jaakko Tuomilehto, MD, at the National Public Health Institute in Helsinki, Finland, argued their findings are supported by the 1991 Systolic Hypertension in the Elderly Program (SHEP), although the prevention of cardiovascular events and stroke was somewhat lower.
Other studies, such as the Appropriate Blood Pressure Control in Diabetes Trial (ABCD) showed higher incidence of MI among the nisoldipine group, but because patients received many different drugs at the same time, it is difficult to determine what accounted for the different risk.
The Finnish study underscores the importance of treating hypertension in diabetics, says Sidney Smith, MD, professor and chief of cardiology at the University of North Carolina Medical School in Chapel Hill and a past president of the American Heart Association.
"The article suggests that long-term calcium antagonists can be used among patients where other forms of antihypertensive therapy are not working," he says. Smith notes that diuretics and ACE inhibitors were also being used by some patients, indicating that combination therapy may have had some bearing on the Finnish results.
He says the burgeoning incidence of hypertension may warrant the use of aggressive therapies such as calcium channel blockers, particularly among diabetics who are so susceptible to vascular disease.
[Bruce Psaty can be reached at (206) 731-5865. Contact Sidney Smith at (919) 966-0732.]
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content