Specific guide to this web site for:
2. Medical Students
3. Science media writers
4. High School & College
1. Harvard led MI study
(J. of Amer. Coll.
4. Amer. J. of Cardio.
review of literature
6. Oat bran study
7. Pregnancy & Alcohol
8. Are Geminis
9. Columbia 'Miracle' Study
Limitations of Meta-Analyses
Large Randomized Clinical
Tale of Two Large
The ALLHAT trial results are only broadly applicable to the treatment of hypertension if the following fallacies are true:
1. The initial treatment with an ACE inhibitor or a calcium channel blocker precluded the use of a diuretic.
2. Starting an ACE inhibitor or calcium channel blocker required stopping diuretic therapy, including in patients with prior myocardial infarction or patients with LVH.
3. An ACE inhibitor and calcium channel blocker could not be used in combination.
4. Equivalent blood pressure endpoints could not be achieved if an ACE inhibitor is used as the initial drug.
of ALLHAT treatment protocol requiring withdrawal of diuretic
therapy and a high threshold to start a diuretic:
The ALLHAT trial protocol resulted in the withdrawal of preexisting diuretic therapy from many of the patients who were assigned to amlodipine or lisinopril treatment protocols. (90% of the patients entered into the trial had prior blood medications
In addition to the patients who had a diuretic withdrawn, there were patients at increased risk for CHF on the basis of prior MI and LVH, who were
routinely not allowed to start a diuretic unless CHF developed or other difficulties arose.
It is not a surprise that CHF or volume overload developed over the course of the trial since diuretic therapy could not be
employed for early signs of volume excess. And in contrast to CHF developing from a less contrived situation, the CHF occurring during the ALLHAT trial was subsequently treated without an increase in mortality when a diuretic could finally be instituted.
One of the lead authors of ALLHAT subsequently published a meta-analysis to support the opinion that diuretics should be the initial therapy for hypertension
(see critique of meta-analysis
ALLHAT hypertension study came to conclusions not supported by the results of
ALLHAT trial critique:
The ALLHAT trial has a extensive data set, but unfortunately the authors'
conclusions go beyond a reasonable interpretation of that data. The authors provoked
immediate controversy when they incorrectly concluded that despite the
limitations of the protocol used in ALLHAT, that the study proved that a
diuretic is the best initial treatment for hypertension.
(Antihypertensive and Lipid-Lowering Treatment to Prevent Heart
Attack Trial) was a large trial. The authors reported in the Journal of the American Medical Association
(JAMA 2002)1 on three blood pressure treatment regimens involving
The ALLHAT authors’ conclusions that their trial proves that a diuretic is
the best initial treatment for high blood pressure are invalid for the following
pressure treatment trials compare specific drug treatment protocols rather
than isolated drugs.
results are only broadly applicable if the following
four aspects of the ALLHAT's blood pressure treatment protocol are relevant to the treatment of hypertension in clinical
* After starting an ACE inhibitor, a diuretic could not be used as the second
* After starting a calcium channel blocker, a diuretic could not be used as a
second treatment agent.
* An ACE inhibitor and calcium channel blocker could not be used in
combination. (Which thereby prohibits the use of a very effective treatment
Equivalent blood pressure control could not be achieved when an ACE inhibitor is
used as the initial drug. (Which is very certainly not true.)
authors substantially underestimate the effect on outcome of the 3mm difference
in blood pressure that occurred between diuretic arm compared to
ACE inhibitor arm. details
Arbitrary emphasis by the ALLHAT authors on difference between treatment arms in
the incidence of CHF, while discounting the importance of the difference in
(Neither was associated with a mortality difference
during the time period of the trial.) details
trial was diuretic withdrawal trial in a patient population including those with
prior MI and with LVH. The high threshold for starting a diuretic in the
treatment arms not initially using
diuretics in the ALLHAT trial would increase the incidence of CHF. See
5. A subsequent meta-analysis of
hypertension trials by some of the ALLHAT authors was significantly flawed:
(Critique of ALLHAT meta-analysis)
that would need to be true for the ALLHAT conclusions to be broadly
applicable. (see right column)
of diuretic withdrawal on the development of CHF in the ALLHAT study. (see
lower right column)
The European Society for Hypertension guidelines for hypertension are quite different from the ALLHAT influenced JNC 7 guidelines for
In contrast to the JNC 7, the European Society for
Hypertension guidelines created in response to the same studies state that the major classes of antihypertensive agents, (including diuretics,
beta-blockers, ACE inhibitors, calcium channel blockers, and angiotensin receptor blockers) are all suitable for initial and maintenance therapy.
from the ALLHAT authors who were on the committee that drafted the JNC 7 guidelines for hypertension led
to a very different outlook: "Thiazide-type diuretics should be used ... in most patients with uncomplicated hypertension, whether alone or combined with drugs from other
ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive
patients randomized to angiotensin-converting enzyme inhibitor or calcium
channel blocker vs. diuretic: the antihypertensive and lipid-lowering treatment
to prevent heart attack trial (ALLHAT). JAMA 2002; 288: 2981-2997