The conclusion that "water pills" are as good as, if not better than, newer and more expensive drugs called ACE inhibitors came in a major government-financed study published Dec. 18 in the Journal of the American Medical Association.
But a large study from Australia, published Thursday in the New England Journal of Medicine, found that ACE inhibitors are somewhat better at preventing heart attacks — at least in men.
The new study is unlikely to end the debate, however — partly because of differences in the two studies, but also because the question is more complex than which drug is better. Many patients, in fact, need two or three drugs to control blood pressure.
For nearly two decades, the question hasn't been "is drug A better than drug B. The question is: Do you have to use A and B, or A, B and C to control blood pressure?" said Dr. James Reed of Morehouse University, a participant in the U.S. study.
About 50 million Americans — one in four adults — are believed to have high blood pressure, which raises the risk of strokes and heart attacks.
Diuretics, used for more than 50 years to treat blood pressure, move water and salt out of the body, reducing the volume of blood so the heart does not have to work as hard to push it around. ACE inhibitors, introduced in 1981, ease blood pressure by reducing production of a chemical that squeezes arteries.
The diuretic used in the U.S. study costs as little as 13 cents a pill in bulk. The ACE inhibitor can range from 35 cents per pill to $1.58.
The Australian study followed 6,083 people ages 65 to 84 for an average of just over four years. Half were randomly assigned to get a diuretic, the other half an ACE inhibitor as their first treatment.
The diuretic hydrochlorothiazide and the ACE inhibitor enalapril were recommended, but each patient's doctor chose drug and dose. Hydrochlorothiazide is sold under dozens of names, and enalapril under three, including Vaseretic and Lexxel.
Drugs in any of three other groups — beta blockers, calcium channel blockers, and alpha blockers — could be added to bring blood pressure down.
Overall, patients in the ACE inhibitor group had 11 percent fewer deaths and "cardiovascular events" such as heart attacks or strokes. But the greater benefit was entirely among the men.
While men in the ACE inhibitor group had 17 percent fewer deaths or cardiovascular events than those in the diuretic group, there was no difference among the women. The men also had nearly twice the number of "events" — 907 versus 524 — even though half the participants were women.
Since this research was not designed to tell whether men get more benefits from ACE inhibitors than women do, more study is needed to see whether that is true, said the researchers, led by Christopher M. Reid, head of the cardiovascular disease prevention unit of the Baker Heart Research Institute in Melbourne.
Reid said much of the disparity between his study and the U.S. one may have been caused by differences among the people enrolled. Blacks, who get less benefit than whites from ACE inhibitors but often do very well on diuretics, made up 35 percent of the U.S. study. Ninety-five percent of the people in the Australian study were white; many of the rest were Asians or Pacific Islanders.
Reid said other factors that may have led to the opposite findings include differences in how the two studies looked at the results.
In addition, Dr. Edward D. Frohlich of Ochsner Clinic Foundations in New Orleans wrote in an accompanying editorial, the U.S. study used a different diuretic and ACE inhibitor than the Australian study.
"These studies are valid — both of them," Frohlich said. "They point to the fact that both classes of drugs are useful. But not every individual patient responds to any one specific drug."
Reed and another participant in the U.S. study, Dr. W. Dallas Hall of Emory University, also said that very few of the measurements in the Australian study met the accepted statistical standard for a clear difference between the groups.
In addition, they noted, doctors and patients all knew what drugs each person was getting. Most major studies, like the U.S. one, are "double blind," meaning neither doctors nor patients know who is taking what, to ensure that expectations do not interfere with results.
By Janet McConnaughey