The Antihyperten-sive and Lipid- Lowering Treatment to
Prevent HeartAttack Trial (ALLHAT) that set out to find
the best antihypertensivedrug for diabetics, has well
and truly put the cat among the pigeons bycasting doubt
on the role of newer classes of blood pressure drugs asfirstline
therapy for both its diabetic subjects and its non-diabetic
controls. Lead author Dr Paul Whelton, an epidemiologist
at Tulane University, Louisiana, sums it up in unequivocal
terms: "Independent of diabetes status, our results
suggest that diuretics are better than ACE inhibitors
and calcium channel blockers in preventing certain cardiovascular
disease complications — especially heart failure
— during initial treatment of high blood pressure."
The researchers are quick to point
out that ACE inhibitors and calcium channel blockers
still have a role to play, when so many patients don't
respond to firstline treatment. But the humble diuretic
or water pill has a justified place in any treatment
regimen, say investigators whose results can be found
in the June 27 issue of the Archives of Internal
Medicine.
The ALLHAT is the largest hypertension
clinical trial ever conducted. Its primary goal was
to establish whether the newer drugs that control hypertension
in otherwise healthy people are also the best choice
for those suffering from type II diabetes. To this end,
researchers from several institutes across Canada and
the US recruited 31,512 hypertensive adults aged 55
or older. Of these patients, 13,101 had type II diabetes,
1,399 had impaired fasting glucose levels, and 17,012
were normoglycemic controls. Each group was randomly
subdivided to receive either the diuretic chlorthalidone,
the ACE inhibitor lisinopril, or the calcium channel
blocker amlodipine.
STUDY
HOLDS WATER
Quite simply, there was not a single category of patient
or endpoint in which the newer, more expensive drugs
outperformed the diuretic. Chlorthalidone was more protective
against heart failure in patients with or without diabetes,
bettering the results achieved with lisinopril by about
17%, and those achieved with amlodipine by about 33%.
Chlorthalidone was at least equally
protective against fatal coronary heart disease or non-fatal
heart attacks in diabetics, in those with impaired fasting
glucose, and in those with normal blood sugar. The diuretic
was also just as protective as the other drugs against
all-cause death, end-stage renal disease or cancer,
in all three types of subject.
This is not the first time the
vast ALLHAT study has posed questions about the benefits
of newer drugs in firstline antihypertensive therapy.
Its initial findings, published in the Journal of the
American Medical Association in December 2002,
caused a stir by suggesting that diuretics were a better
option in normoglycemic patients. The latest findings
show that the same appears to apply to firstline treatment
of diabetics. Since about three-quarters of type II
diabetics have high blood pressure, this conclusion
could point to treatment changes for huge numbers of
patients. The debate over the best firstline treatment
for hypertension has been difficult to resolve and ALLHAT
remains by far the best and largest study to compare
these drugs head-to-head.
Arch Intern Med Jun 27, 2005;165(12):1401-9
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