TNT Trial
Treating to New Targets Study
Presented at
The American College of Cardiology
Scientific Sessions 2005
Presented by Dr. John C. LaRosa
TNT Trial
10,003 patients with stable coronary heart disease
Age 35-75 years, LDL between 130 and 250 mg/dL, triglyceride ≤ 600 mg/dL
19% female, mean age 60.3 years
All received atorvastatin 10 mg during 8 week open-label run-in period
Atorvastatin 80 mg
n=4,995
Atorvastatin 10 mg
n=5,006
Primary Endpoint: Major cardiovascular event defined as coronary heart death
(CHD) , nonfatal M, resuscitated cardiac arrest, and fatal or nonfatal stroke at a
mean follow-up of 4.9 years.
Secondary Endpoint: Major coronary events, cerebrovascular events,
hospitalization for congestive heart failure (CHF), all-cause mortality, peripheral
artery disease, any cardiovascular event, any coronary event
www. Clinical trial results.org
Presented at ACC 2005
TNT Trial: Primary endpoint
Primary Composite of CHD death,
nonfatal MI, resuscitated cardiac arrest,
and fatal or nonfatal stroke
12%
Hazard Ratio [HR]=0.78
p<0.001
10.9%
8.7%
8%
• The primary composite
endpoint of CHD death, nonfatal
MI, resuscitated cardiac arrest,
and fatal or nonfatal stroke was
lower in the high-dose
atorvastatin 80 mg group at a
mean follow-up of 4.9 years.
4%
0%
High-dose
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Low-dose
Presented at ACC 2005
TNT Trial: Primary Endpoint
The individual components of the primary endpoint were also lower or tended to be
lower in the high-dose group compared to the low-dose group with the exception of
resuscitation after cardiac arrest, which was the equal in both groups.
8%
p=0.004
6.2%
6%
4.9%
p=0.02
4%
p=0.09
2.0%
3.1%
2.5%
2.3%
2%
p=0.89
0.5%
0.5%
0%
CHD death
Nonfatal MI
High-dose
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Resuscitation
after cardiac
arrest
Stroke
Low-Dose
Presented at ACC 2005
TNT Trial: Secondary Endpoint
•The components of the secondary endpoint that were lower in the high-dose
group included: major coronary events, cerebrovascular events, and
hospitalization for CHF. All-cause mortality and peripheral artery disease were
equivalent in both high and low dose groups.
Major Coronary Events
p=0.002
9%
8.3%
6.7%
Cerebrovascular
Events
p=0.007
All-cause
Mortality
Peripheral Artery
Disease
p=0.92
p=0.76
CHF
5.7%
6%
5.0%
p=0.01
5.6%
5.5%
5.6%
3.9%
3.3%
3%
2.4%
0%
High-dose
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Low-Dose
Presented at ACC 2005
TNT Trial
Persistent elevations in liver aminotransferase levels, treatment-related adverse
events, and study drug discontinuation due to adverse events were all higher in the
high-dose group compared to the low-dose group.
p<0.001
9%
p<0.001
8.1%
7.2%
5.8%
6%
5.3%
p<0.001
3%
1.2%
0.2%
0%
Liver Aminotransferase
High-dose
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Adverse Events
Drug discontinuation
Low-Dose
Presented at ACC 2005
TNT Trial: Summary
• Among patients with stable coronary heart disease treatment with
high-dose atorvastatin to achieve an LDL below 100 mg/dL was
associated with a reduction in the primary composite endpoint of major
cardiovascular events at 5 years compared with treatment with lowdose atorvastatin to achieve an LDL of approximately 100 mg/dL.
• There was no difference in all-cause mortality in the high-dose
compared to the low-dose group.
• Persistent elevations in liver aminotransferase, treatment-related
adverse events, and study drug discontinuation all occurred more
frequently in the high-dose atorvastatin group compared to the lowdose group. There was no difference by treatment group in persistent
CK elevations, myalgia, or rhabdomyolysis.
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Presented at ACC 2005
TNT Trial: Summary cont’d
• The overall safety profile was consistent with other large atorvastatin trials, and
was likely relatively low due to the exclusion of the 131 patients with abnormal
liver-function tests or myalgia during the run-in phase. Despite the exclusion of
these patients, persistent with abnormal liver-function tests were more frequent
with the 80 mg atorvastatin group, suggesting close monitoring is warranted in
pateints treated with this dose.
• In the PROVE-IT / TIMI 22 trial, aggressive lipid lowering with atorvastatin 80 mg
was associated with a reduction in cardiovascular events compared with standard
LDL lowering with pravastatin in patients with acute coronary syndrome.
• The results from TNT confirm what was observed in PROVE-IT / TIMI 22 and
suggest that aggressive lipid lowering to LDL levels <75 mg/dL reduces
cardiovascular events in patients with stable coronary artery disease.
www. Clinical trial results.org
Presented at ACC 2005