Recent Clinical Trial Results:
A Critique
Ronald G. Victor, M.D.
Chief, Hypertension Division
Norman & Audrey Kaplan Chair
SO HWESTERN Medical Center
How well have recent trials
addressed 3 questions?
1. Does drug class matter?
2. BP targets: how low should we go?
3. Can HTN be prevented?
Controversies in CV Medicine
Management of Hypertension:
Is It the Pressure or the Drug?
Drug Counts Its Only the BP
Peter S. Sever William J. Elliott
Neil R. Poulter M. Charlotte Jonsson
Henry R. Black
Sever et al. Circulation. 2006;113:2754-2772 (A).
Angiotensin II
AT1R
Superoxide
Inflammation
Cell Growth, Fibrosis
Aldosterone, NE
BP ⇧Glucose Atherosclerosis
Remodeling of Plaque
Heart & Vessels Progression
MI & Stroke
Victor, J Clin Hypertens,
2007 in press
Death
Hypothesis
For equivalent reductions in BP,
RAAS blockers provide more target
organ protection and prevent more
CV events than do other antihypertensives
Recent ACEI trials
Recent ARB trials
b-blockers as comparators
Recent ACEI Trials
BP Titration Trials ACEI Add-on Trials
ALLHAT HOPE
ASCOT EUROPA
PEACE
ALLHAT
Smaller Fall in BP With ACEI but Identical Outcome
Chlorthalidone Amlodipine Lisinopril
Blood Pressure 1° CHD Outcome
150 .20
145
Systolic .16
140 n=33,357
135
.12
mm Hg
130
BP=2/1
%
90 P CCB?)
Placebo
• longer follow-up
Cumulative Incidence of HTN (%)
100
Candesartan 16 mg qd
80
Active Treatment in
• younger patients
Candesartan Arm
60
40 Year 4
P<.007
RRR=15.6%
20 Year 2
P<.001
RRR=66.3%
0
0 1 2 3 4
Study Year
TROPHY=Trial of Preventing Hypertension.
Julius S, Nesbitt, S et al. N Engl J Med. 2006;354:1685-1697 (A).
CONCLUSION--Future Needs:
1. ABPM & central aortic BP
2. Larger sample size achieving lower
BP targets
3. Younger study patients (at high risk)
4. Dissociate trial objectives & design
from financial or economic agenda of
the funding agencies.