antihypertensive and lipid-lowering treatment to prevent heart attack trial jama 2002;288:2981-2997...
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Antihypertensive and Lipid-Lowering Treatment to Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack TrialPrevent Heart Attack Trial
Antihypertensive and Lipid-Lowering Treatment to Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack TrialPrevent Heart Attack Trial
JAMA 2002;288:2981-2997JAMA 2002;288:2981-2997
ALLHATALLHAT
www. Clinical trial results.org
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
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
DiureticChlorthalidone 12-25 mg/day
(n=15,255)
DiureticChlorthalidone 12-25 mg/day
(n=15,255)
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
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
ALLHATALLHATALLHATALLHAT
JAMA 2002;288:2981-2997JAMA 2002;288:2981-2997
Calcium Channel Blocker
Amlodipine 2.5-10 mg/day
(n=9,048)
Calcium Channel Blocker
Amlodipine 2.5-10 mg/day
(n=9,048)
ACE Inhibitor Lisinopril
10-40 mg/day(n=9,054)
ACE Inhibitor Lisinopril
10-40 mg/day(n=9,054)
Alpha BlockerDoxazosin*2-8 mg/day(n=9,061)
Alpha BlockerDoxazosin*2-8 mg/day(n=9,061)
* Discontinued prior to study completion
www. Clinical trial results.org
11.5% 11.3%
0%
5%
10%
15%
11.5% 11.3%
0%
5%
10%
15%
Chlorthalidone vs AmlodipinePrimary Endpoint
RR = 0.98p = 0.65
Chlorthalidone vs AmlodipinePrimary Endpoint
RR = 0.98p = 0.65
ALLHAT: Primary Endpoint*ALLHAT: Primary Endpoint*ALLHAT: Primary Endpoint*ALLHAT: Primary Endpoint*
ChlorthalidoneChlorthalidone
JAMA 2002;288:2981-2997JAMA 2002;288:2981-2997
AmlodipineAmlodipine
11.5% 11.4%
0%
5%
10%
15%
11.5% 11.4%
0%
5%
10%
15%
* Primary Endpoint = Fatal CHD or nonfatal MI
Chlorthalidone vs LisinoprilPrimary Endpoint
RR = 0.99p = 0.81
Chlorthalidone vs LisinoprilPrimary Endpoint
RR = 0.99p = 0.81
ChlorthalidoneChlorthalidone LisinoprilLisinopril
www. Clinical trial results.org
17.3% 16.8%
0%
5%
10%
15%
20%17.3% 16.8%
0%
5%
10%
15%
20%
All Cause MortalityRR = 0.96p = 0.20
All Cause MortalityRR = 0.96p = 0.20
ALLHAT: Secondary EndpointsALLHAT: Secondary EndpointsALLHAT: Secondary EndpointsALLHAT: Secondary Endpoints
ChlorthalidoneChlorthalidone
JAMA 2002;288:2981-2997JAMA 2002;288:2981-2997
AmlodipineAmlodipine
7.7%
10.2%
0%
5%
10%
15%
7.7%
10.2%
0%
5%
10%
15%
Heart FailureRR = 1.38p < 0.001
Heart FailureRR = 1.38p < 0.001
ChlorthalidoneChlorthalidone AmlodipineAmlodipine
Chlorthalidone vs AmlodipineChlorthalidone vs Amlodipine
www. Clinical trial results.org
5.6%6.3%
0%
2%
4%
6%
8%
10%
5.6%6.3%
0%
2%
4%
6%
8%
10%
17.3% 17.2%
0%
5%
10%
15%
20%
17.3% 17.2%
0%
5%
10%
15%
20%
All Cause MortalityRR = 1.00p = 0.90
All Cause MortalityRR = 1.00p = 0.90
ALLHAT: Secondary EndpointsALLHAT: Secondary EndpointsALLHAT: Secondary EndpointsALLHAT: Secondary Endpoints
ChlorthalidoneChlorthalidone
JAMA 2002;288:2981-2997JAMA 2002;288:2981-2997
LisinoprilLisinopril
7.7%8.7%
0%
5%
10%
15%
7.7%8.7%
0%
5%
10%
15%
Heart FailureRR = 1.19p < 0.001
Heart FailureRR = 1.19p < 0.001
Chlorthalidone vs LisinoprilChlorthalidone vs Lisinopril
ChlorthalidoneChlorthalidone LisinoprilLisinopril ChlorthalidoneChlorthalidone LisinoprilLisinopril
StrokeRR = 1.15p = 0.02
StrokeRR = 1.15p = 0.02
www. Clinical trial results.org
ALLHAT: SummaryALLHAT: SummaryALLHAT: SummaryALLHAT: 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
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
www. Clinical trial results.org
ALLHAT: LimitationsALLHAT: LimitationsALLHAT: LimitationsALLHAT: 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
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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