ALLHAT
Antihypertensive and Lipid-Lowering Treatment to
Prevent Heart Attack Trial
JAMA 2002;288:2981-2997
ALLHAT
42,418 patients with hypertension




SBP >140mmHg and/or DBP >90 mmHg OR
Took medication for hypertension and had at least one additional risk factor for CHD
Age >55 years
NHLBI funded trial
Calcium Channel
Blocker
Amlodipine
2.5-10 mg/day
(n=9,048)
Diuretic
Chlorthalidone
12-25 mg/day
(n=15,255)
ACE Inhibitor
Lisinopril
10-40 mg/day
(n=9,054)
Alpha Blocker
Doxazosin*
2-8 mg/day
(n=9,061)
Endpoints:



Primary – Fatal coronary heart disease and nonfatal MI
Secondary – All-cause mortality, stroke, and major
cardiovascular disease events (CHF, coronary
revascularization, angina, and peripheral artery disease)
Mean follow-up 4.9 years
www. Clinical trial results.org
* Discontinued prior to study completion
JAMA 2002;288:2981-2997
ALLHAT: Primary Endpoint*
15%
Chlorthalidone vs Amlodipine
Primary Endpoint
RR = 0.98
p = 0.65
11.5%
15%
11.5%
11.3%
10%
10%
5%
5%
0%
0%
Chlorthalidone
Amlodipine
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Chlorthalidone vs Lisinopril
Primary Endpoint
RR = 0.99
p = 0.81
Chlorthalidone
* Primary Endpoint = Fatal CHD or nonfatal MI
11.4%
Lisinopril
JAMA 2002;288:2981-2997
ALLHAT: Secondary Endpoints
20%
Chlorthalidone vs Amlodipine
All Cause Mortality
RR = 0.96
15%
p = 0.20
17.3%
Heart Failure
RR = 1.38
p < 0.001
16.8%
10.2%
15%
10%
7.7%
10%
5%
5%
0%
0%
Chlorthalidone
Amlodipine
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Chlorthalidone
Amlodipine
JAMA 2002;288:2981-2997
ALLHAT: Secondary Endpoints
Chlorthalidone vs Lisinopril
20%
All Cause Mortality
RR = 1.00
p = 0.90
17.3%
15%
Heart Failure
RR = 1.19
p < 0.001
10%
Stroke
RR = 1.15
p = 0.02
17.2%
8%
15%
10%
8.7%
7.7%
6.3%
6%
5.6%
10%
4%
5%
5%
2%
0%
Chlorthalidone Lisinopril
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0%
Chlorthalidone Lisinopril
0%
Chlorthalidone Lisinopril
JAMA 2002;288:2981-2997
ALLHAT: Summary
Prespecified primary endpoint of fatal CHD or nonfatal MI did not differ
between initial use of the diuretic chlorthalidone vs initial use of the
ACE inhibitor lisinopril or the calcium antagonist amlodipine for the
treatment of hypertension
– Secondary outcome of heart failure was lower among patients treated with
chlorthalidone vs lisinopril or amlodipine
– Each of the 3 drugs reduced blood pressure from baseline, although
chlorthalidone use was associated with larger SBP reductions vs lisinopril or
amlodipine
– Increased risk of heart failure in lisinopril arm unexpected and in contrast to
the benefits of ACE inhibitors observed in other trials for the treatment of heart
failure such as SOLVD
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ALLHAT: Limitations
Diabetic risk
– Important side effect in the chlorthalidone arm was higher fasting glucose
levels vs lisinopril or amlodipine arms in all patients and in non-diabetics
– Impact of chlorthalidone on diabetes and cardiovascular disease may not be
fully manifested in the relatively short follow-up period of 4 years
– ACE inhibitors have previously been associated with a reduction in the
development of diabetes and the progression of diabetic nephropathy
Add-on therapy
– ACE inhibitor arm potentially at a disadvantage since the first add-on therapy
specified by the trial treatment algorithm for this arm was a beta-blocker
rather than a diuretic or calcium channel blocker, both of which are more
commonly used in clinical practice
Large crossover rate by 4 year follow-up
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