Transcript Thumbs Up, Thumbs Down. ALLHAT

Clinical Trial Commentary
ALLHAT
Dr Eric Topol
Chairman and Professor, Department of Cardiology
Director of the Joseph J Jacobs Center for Thrombosis
and Vascular Biology at the Cleveland Clinic
Dr Robert Califf
Professor of Cardiology
Associate Vice Chancellor for
Clinical Research at Duke University
ALLHAT
The Antihypertensive and Lipid-Lowering
treatment to prevent Heart Attack Trial
Eligibility
- Men and women > 55 years with systolic
BP > 140 mmHg and/or diastolic BP > 90 mm Hg,
or medicated for hypertension
- at least one additional risk factor for coronary
heart disease (CHD)
Risk factors for CHD
-myocardial infarction, stroke, left ventricular
hypertrophy by ECG or echo, type II diabetes,
smoking, low HDL
ALLHAT
Patients
42 448 participants recruited from 625 centers
Patients were randomized to the following
antihypertensive treatments (relative number of
patients per group in parentheses).
chlorthalidone (1.7)
lisinopril (1)
amlodipine (1)
doxazosin (1)
A substudy looks at lipid-lowering using
pravastatin.
Treatment goal
BP systolic < 140 and diastolic < 90 mm Hg
ALLHAT
Primary endpoint
composite fatal CHD and nonfatal MI
Secondary endpoints
(1) all-cause mortality
(2) combined CHD (death, nonfatal MI,
revascularization, hospitalization for angina)
(3) stroke
(4) combined CVD
The doxazosin arm was discontinued in January
2000 based on the recommendations of an
independent review committee.
For the remaining treatment arms, follow-up is
scheduled to end in March 2002.
ALLHAT
doxazosin vs chlorthalidone
Outcomes for blood pressure control
Year of study
chlorthalidone
doxazosin
Baseline
145/83
145/84
1
137/79
140/79
2
136/78
138/78
4
135/76
137/76
Mean blood pressure, seated
ALLHAT Officers and Coordinators for the ALLHAT
Collaborative Research Group. JAMA 2000;283:1967-1975
ALLHAT
doxazosin vs chlorthalidone
Outcomes for primary and secondary endpoints
Relative risk (RR) for doxazosin shown
Endpoint
CHD
RR
1.03
95% CI
(0.9 - 1.17)
p value
0.71
all-cause
mortality
1.03
(0.9 - 1.15)
0.56
Combined CVD
1.25
(1.17-1.33)
<0.0001
CHF
2.04
(1.79-2.32)
<0.0001
Non-CHF
events
1.13
(1.06-1.21)
<0.001
Stroke
1.19
(1.01-1.40)
0.04
ALLHAT Officers and Coordinators for the ALLHAT
Collaborative Research Group. JAMA 2000;283:1967-1975
ALLHAT
Study outcome
Compared with doxazosin, chlorthalidone
reduces the risk for combined CVD events,
particularly CHF, in high-risk hypertensive
patients.
The study did not have a placebo arm, so the
effect of doxazosin compared to no treatment
cannot be determined.
The use of blood pressure as a surrogate
marker in the treatment of hypertension,
without regard for the antihypertensive drug
used, is called into question.
ALLHAT
“To me the take home message to the
practitioner is that if you have a patient
on an alpha-blocker alone or doxazosin
alone in particular, and there's an
alternative, and it hasn't been a
complicated step to get where you are in
the antihypertensive regimen, then switch
to the other alternative.”
Dr Robert Califf
Professor of Cardiology
Associate Vice Chancellor for
Clinical Research at Duke University
ALLHAT
“So it's ironic too that here is a men's health
drug, to improve quality of life for patients
with large prostates, and coming out the
same week as the Women's Health Initiative
for estrogen replacement. You wonder all
kinds of things that are in the pharmacologic
environment that because they haven't been
adequately tested when they get to large
scale trials you start to learn about the truth.”
Dr Eric Topol
Chairman and Professor
Department of Cardiology
Cleveland Clinic
Demographics in
cardiology
The average American can now be expected to
live until age 76.4 (80 years for females, 73
years for males).
In 1995, 737 000 deaths were secondary to
heart disease (HD). 615 000 or 84% of these
deaths occurred in people 65 years or older.
The population is projected to increase 43.4%
and deaths attributable to HD are projected to
increase by 112.7% over the next 50 years.
Foot DK, et al. J Am Coll Cardiol 2000;35:10667-1081