(ALLHAT) Leggere bene.

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)
The ALLHAT Officers and
Coordinators for the ALLHAT
Collaborative Research Group
TREATMENT AND COMPLICAtions
among the 50 to 60 million
people in the United States
with hypertension are estimated
to cost $37 billion annually, with
antihypertensive drug costs alone accounting
for an estimated $15.5 billion
per year.1 Antihypertensive drug
therapy substantially reduces the risk
of hypertension-related morbidity and
mortality.2-6 However, the optimal
choice for initial pharmacotherapy of
hypertension is uncertain.7
Earlier clinical trials documented the
benefit of lowering blood pressure (BP)
using primarily thiazide diuretics or
-blockers.2,3,8 After these studies, several
newer classes of antihypertensive
agents (ie, angiotensin-converting enzyme
[ACE] inhibitors, calcium channel
blockers [CCBs], -adrenergic
blockers, and more recently angiotensin-
receptor blockers) became available.
Over the past decade, major placebo-
controlled trials have documented
that ACE inhibitors and CCBs reduce
cardiovascular events in individuals
with hypertension.9-11 However, their
relative value compared with older, less
expensive agents remains unclear.
There has been considerable uncertainty
regarding effects of some classes
of antihypertensive drugs on risk of
Author Affiliations: ALLHAT Authors, Their Financial
Disclosures, and Group Members are listed at the
end of this article.
Corresponding Authors and Reprints: Jackson T.
Wright, Jr, MD, PhD, Case Western Reserve University,
General Clinical Research Center, Suite 7311,
Horvitz Tower, 11000 Euclid Ave, Cleveland, OH
44106-5041 (e-mail: jxw20@po.cwru.edu); Barry R.
Davis, MD, PhD, University of Texas-Houston Health
Science Center, School of Public Health, 1200 Herman
Pressler St, Suite E801, Houston, TX 77030
(e-mail: bdavis@sph.uth.tmc.edu).
Context Antihypertensive therapy is well established to reduce hypertensionrelated
morbidity and mortality, but the optimal first-step therapy is unknown.
Objective To determine whether treatment with a calcium channel blocker or an
angiotensin-converting enzyme inhibitor lowers the incidence of coronary heart disease
(CHD) or other cardiovascular disease (CVD) events vs treatment with a diuretic.
Design The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack
Trial (ALLHAT), a randomized, double-blind, active-controlled clinical trial conducted
from February 1994 through March 2002.
Setting and Participants A total of 33357 participants aged 55 years or older with
hypertension and at least 1 other CHD risk factor from 623 North American centers.
Interventions Participants were randomly assigned to receive chlorthalidone, 12.5
to 25 mg/d (n=15255); amlodipine, 2.5 to 10 mg/d (n=9048); or lisinopril, 10 to 40
mg/d (n=9054) for planned follow-up of approximately 4 to 8 years.
Main Outcome Measures The primary outcome was combined fatal CHD or nonfatal
myocardial infarction, analyzed by intent-to-treat. Secondary outcomes were allcause
mortality, stroke, combined CHD (primary outcome, coronary revascularization,
or angina with hospitalization), and combined CVD (combined CHD, stroke, treated angina
without hospitalization, heart failure [HF], and peripheral arterial disease).
Results Mean follow-up was 4.9 years. The primary outcome occurred in 2956 participants,
with no difference between treatments. Compared with chlorthalidone (6-
year rate, 11.5%), the relative risks (RRs) were 0.98 (95% CI, 0.90-1.07) for amlodipine
(6-year rate, 11.3%) and 0.99 (95% CI, 0.91-1.08) for lisinopril (6-year rate,
11.4%). Likewise, all-cause mortality did not differ between groups. Five-year systolic
blood pressures were significantly higher in the amlodipine (0.8 mm Hg, P=.03)
and lisinopril (2 mm Hg, P .001) groups compared with chlorthalidone, and 5-year
diastolic blood pressure was significantly lower with amlodipine (0.8mmHg, P .001).
For amlodipine vs chlorthalidone, secondary outcomes were similar except for a higher
6-year rate of HF with amlodipine (10.2% vs 7.7%; RR, 1.38; 95% CI, 1.25-1.52).
For lisinopril vs chlorthalidone, lisinopril had higher 6-year rates of combined CVD (33.3%
vs 30.9%; RR, 1.10; 95% CI, 1.05-1.16); stroke (6.3% vs 5.6%; RR, 1.15; 95% CI,
1.02-1.30); and HF (8.7% vs 7.7%; RR, 1.19; 95% CI, 1.07-1.31).
Conclusion Thiazide-type diuretics are superior in preventing 1 or more major forms
of CVD and are less expensive. They should be preferred for first-step antihypertensive
therapy.
JAMA. 2002;288:2981-2997