ALLHAT
New Research Opportunities
www.allhatresearch.org
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ALLHAT
• ALLHAT
New Opportunities
(www.allhat.org)–
– Largest antihypertensive treatment trial
– Second largest lipid-lowering trial ever conducted,
– Landmark cost-effectiveness study.
• Large size and diversity of participants, varied practice settings,
and primary and secondary outcomes makes the ALLHAT data
set highly useful for epidemiologic investigations.
• In the past, ALLHAT data were available only to ALLHAT
investigators. Now this resource is available to the wider
scientific community. New research to use this valuable data
collected since 1994 is encouraged, especially for new
investigators early in their research careers.
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ALLHAT
New Investigator
A new investigator is one who
• Is interested in using ALLHAT data for the first time
• May be seeking funding for the first time, or may already have
funding
• May be affiliated either with an institution never before
associated with ALLHAT, or an institution that has participated in
ALLHAT in the past.
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ALLHAT
Unique Strengths I
• Largest antihypertensive treatment trial and
second largest lipid-lowering trial ever
conducted.
• Well-designed and conducted clinical research,
landmark cost-effectiveness study.
• Large size and diversity of participants, varied
practice settings, and primary and secondary
outcomes makes the ALLHAT data set highly
useful for epidemiologic investigations.
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ALLHAT
Unique Strengths II
• Randomized active phase lasted 5 years
• Large size:
– 42,418 hypertensive participants enrolled
– 10,355 enrolled in lipid-lowering sub-cohort
• Varied practice setting
– 623 clinical sites in the US, Puerto Rico, U.S. Virgin
Islands, and Canada
• Drug comparisons
– Four antihypertensive treatment arms
– Two lipid-lowering treatment arms
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ALLHAT
Unique Strengths III
• Diversity of participants
– Ages ≥55 years with ≥ 1 other CVD risk factor
besides hypertension
– All races
– Co-morbid conditions
• Many variables recorded
• Outcome data recorded for:
– In-trial CVD and non-CVD events (1994-2002)
– Post-trial (2002-2006).
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ALLHAT
Types of Data Available
• Data collected during the active phase of the ALLHAT clinical trial
1994-2002.
• Laboratory analyses conducted by the ALLHAT Central
Laboratory.
• Outcome data collected for some ALLHAT participants during
post-trial passive follow-up (2002-2006) , after the active phase of
the clinical trial ended.
• ECG data collected at baseline and biannually
• Frozen serum samples
• Genetic material
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ALLHAT
How You Can Use
ALLHAT Data
You may use ALLHAT data to either:
• Propose a new paper topic for publication in a peerreviewed journal
• Propose a new ALLHAT-related study to an external
funding agency
– May involve collecting new information from outside
databases (e.g., CMS)
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ALLHAT
How You Can Use
ALLHAT Data
• STEP 1: Check to see that your topic has not already
been addressed.
• STEP 2: Submit a Concept Proposal to Dr. Ellen
Breckenridge (Ellen.Breckenridge@uth.tmc.edu).
• STEP 3: If your concept is approved, a Coordinating
Center liaison will be assigned. You will be invited to
identify an ALLHAT sponsor and provide a more
detailed proposal. Upon request, the Coordinating
Center can help identify an ALLHAT sponsor.
• STEP 4: The ALLHAT study leadership will review the
detailed proposal. If accepted, a timetable will be
developed and work can proceed.
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ALLHAT
How You Can Obtain
ALLHAT Data
• Collaborate with an ALLHAT sponsor and the
Coordinating Center to analyze data and write
a paper or a project proposal.
• Request a data set to produce your own data
runs for your paper or project.
• Request a limited access data set from NHLBI
at https:\\biolincc.nhlbi.nih.gov/home
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ALLHAT
www.allhatresearch.org
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ALLHAT
Research Already
Accomplished I
Final results published in 2002. See
www.allhat.org for details on publications and
presentations. Papers have addressed
• Blood pressure
– predictors of blood pressure response overall
– predictors within randomized treatment groups.
• Diabetes
– ALLHAT results by diabetes subgroups
– diabetes incidence by randomized treatment group.
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ALLHAT
Research Already
Accomplished II
• Heart Failure
– validity of the ALLHAT heart failure outcome,
– heart failure by randomized treatment group,
– heart failure with preserved and reduced ejection
fraction, and
– post-heart failure mortality risk.
• Chronic Kidney Disease
– ALLHAT results by CKD subgroups,
– CKD incidences by randomized treatment group, and
– the prognostic value of CKD groups for
cardiovascular and renal outcomes.
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ALLHAT
Research Already
Accomplished III
• Atrial Fibrillation
– incidence of atrial fibrillation by randomized
treatment group.
• Metabolic Syndrome
– ALLHAT results by metabolic syndrome subgroups
overall
– ALLHAT results by race subgroups.
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ALLHAT
Contact Us
• For additional information or further assistance, please contact
Ellen Breckenridge, PhD, JD, MPH
ALLHAT Assistant Project Manager
ellen.breckenridge@uth.tmc.edu
713-500-9508
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ALLHAT
Antihypertensive
Trial Design
• Randomized, double-blind, clinical trial of 42,418 participants
with high blood pressure comparing 4 commonly-used
antihypertensives.
• ALLHAT investigated whether there was a difference in fatal CHD
& nonfatal MI among patients randomized to CCB, ACEI, or alphablocker compared to a diuretic.
• ALLHAT also examined differences in secondary endpoints,
including:
– All-cause mortality, stroke, combined CHD (primary outcome,
coronary revascularization, hospitalized angina)
– combined CVD (combined CHD, stroke, other treated angina,
HF [fatal, hospitalized, or treated non-hospitalized], and
peripheral arterial disease)
– renal endpoints, and cancer
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ALLHAT
Baseline Characteristics
and Follow-up
Baseline
Follow-up
N
42,418
Known alive
82%
Mean SBP/DBP
146 / 84
Confirmed dead
15%
Mean age, y
67
Lost / refused
3%
Black, %
36
99%
Women, %
47
Person-years
(% obs/exp)
Current smoking %
22
History of CHD, %
26
Type 2 diabetes, %
36
On antihypertensive treatment, %
92
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ALLHAT
Doxazosin Arm
Terminated Early
• Futility of finding a significant difference
for primary CHD outcome
• Statistically significant 20 percent higher
rate of major secondary endpoint,
combined CVD outcomes (80% higher rate
of heart failure)
Hypertension. 2003;42:239-246.
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ALLHAT BP Results by Treatment Group
Amlodipine
Lisinopril
150
90
145
85
mm Hg BP
mm Hg BP
Chlorthalidone
140
80
135
75
130
70
0
1
2
3
Years
4
5
6
0
1
2
3
Years
4
5
Compared to chlorthalidone:
Compared to chlorthalidone:
SBP significantly higher in the
amlodipine group (~1 mm Hg) and
the lisinopril group (~2 mm Hg).
DBP significantly lower in the
amlodipine group (~1 mm Hg),
similar in the lisinopril group.
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Summary of Outcomes
Relative Risks and 95% CI
ALLHAT
Amlodipine / Chlorthalidone
Lisinopril / Chlorthalidone
CHD
0.98 (0.91, 1.08)
0.99 (0.91, 1.08)
Death
0.96 (0.89, 1.02)
1.00 (0.94, 1.08)
CCHD
1.00 (0.94, 1.07)
1.05 (0.98, 1.11)
Stroke
0.93 (0.82, 1.06)
1.15 (1.02, 1.30)
CCVD
1.04 (0.99, 1.09)
1.10 (1.05, 1.16)
HF
1.38 (1.25, 1.52)
1.19 (1.07, 1.31)
0.50
Amlodipine
Better
1
2
Chlorthalidone
Better
0.50
Lisinopril
Better
1
2
Chlorthalidone
Better
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ALLHAT
Subgroup Comparisons
Results were consistent across age, race,
gender, and baseline diabetes subgroups,
except:
– Stroke
• Black L/C RR (95% CI) = 1.40 (1.17 – 1.68)
• Non-Black L/C RR (95% CI) = 1.00 (0.85 – 1.17)
– Combined CVD
• Black L/C RR (95% CI) = 1.19 (1.09 – 1.30)
• Non-Black L/C RR (95% CI) = 1.06 (1.00 – 1.13)