Review of the Design and Initial Findings for Prespecified Outcomes and Subgroups

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ALLHAT Revisited How have
the Initial Findings Held Up Five Years Later?

• Review of the Design and Initial Findings for
  Pre-specified Outcomes and Subgroups

Paul K. Whelton, M.D., M.Sc. Loyola University
Medical Center Maywood, Illinois, U.S.A.
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Predefined Subgroups -Age (lt65 y
65y) -Gender -Race (Black Non-Black) -Diabetes
(Diabetic Non-Diabetic)
BP Trial Primary End Points -Fatal CHD
Non-Fatal MI BP Trial Secondary End Points
-All-cause mortality -Stroke -Combined CHD
Fatal CHD, non-fatal MI, coronary
revascularization, hospitalized angina -Combined
CVD combined CHD, stroke, lower extremity
revascularization, treated angina, fatal /
hospitalized / treated heart failure (HF),
hospitalized or outpatient peripheral arterial
disease (PAD) -Other renal (reciprocal serum
creatinine, ESRD, estimated GFR) and cancer
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-Primary sponsor NIH-NHLBI -Concurrent support
from the VA -Assistance from pharmaceutical
companies but no role in scientific conduct of
trial
-623 Clinical Centers -USA, Canada,
Caribbean -Diverse practice settings
Program Office, NHLBI
CTC, UT
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Baseline Characteristics(33, 357 Participants)
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Treatment Regimen
Doses were escalated in an attempt to achieve a
BP lt140/80 mm Hg
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Percent Taking Blinded Study Drug or Drug from
Same Class
Lisinopril
Chlorthalidone
Amlodipine
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Mean Systolic and Diastolic BP,by Treatment Group
150
Systolic BP
145
140
Amlodipine
135
Lisinopril

mm Hg
90
Chlorthalidone
Diastolic BP
85
80
Lisinopril
75
Chlorthalidone
70
Amlodipine
Months of Follow-up
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Biochemical ResultsSr. Cholesterol Potassium
plt.05 compared to chlorthalidone Ann Intern
Med. 1999130461-470
JAMA 20022882981-97
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Biochemical ResultsFasting Glucose
plt.05 compared to chlorthalidone
JAMA 20022882981-97
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Summary of Outcomes Relative Risks (95 CI)
JAMA 20022882981-97
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Stroke, by Treatment Group. RR (95 CI) in
Predefined Subgroups
Amlodipine/Chlorthalidone
Lisinopril/Chlorthalidone
P .01 for interaction
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ALLHAT BP Trial Design and Initial Findings
Summary

• 5 y efficacy trial of antihypertensive drug
  regimens in 42,418 participants. Regimens
  designed to be similar except for double blinded
  treatment with
• chlorthalidone (C), amlodipine (A), lisinopril
  (L) or doxazosin
• Doxazosin comparison stopped prematurely due to
  difference in CVD events
• Baseline characteristics similar in 33,357 C, A
  and L participants
• Strong representation of important subgroups
• Excellent adherence to assigned study drugs
• The three regimens differed slightly but
  significantly in BP control, Sr. Cholesterol, Sr.
  Potassium and fasting blood sugar
• No difference in the primary outcome for C vs. A
  or C vs. L
• C was better than A for HF
• C was better than L for stroke, combined CVD
  events and HF. There was a significant C vs. L
  treatment X race interaction for the stroke
  outcome.
• The ALLHAT findings suggest thiazide-type
  diuretics are the preferred first-step
  antihypertensive drug therapy unless there is a
  contraindication to their use