TNT: New data on intensive lipid lowering in stable CHD patients

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TNT New data on intensive lipid lowering in
stable CHD patients
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TNT Treating to New Targets
Hypothesis Lowering LDL-C levels to well below
100 mg/dL could yield an incremental clinical
benefit Participants 10,001 patients with stable
CHD and LDL-C 130-250 mg/dL Treatments Atorvasta
tin 10 mg and 80 mg Median follow-up 4.9
years Primary outcome CHD death, MI,
resuscitation after cardiac arrest,
fatal/nonfatal stroke
LaRosa JC et al. N Engl J Med. 2005352.
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Benefit of intensive LDL-C lowering Accumulating
evidence
30
4S
Statin
Placebo
25
4S
20
Event()
15
LIPID
LIPID
CARE
CARE
10
HPS
HPS
5
0
210
190
170
150
130
110
90
70
0
LDL cholesterol (mg/dL)
LaRosa JC et al. N Engl J Med. 2005352.
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TNT Design

• Patient population
• 250 centers in 14 countries(N 10,001)
• LDL 130250 mg/dL
• TG lt600 mg/dL

Atorvastatin 10 mg
Atorvastatin 10 mg
Atorvastatin 80 mg
4.9 years
8 weeks
Waters DD et al. Am J Cardiol. 200493154-8.
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TNT Baseline characteristics
Atorvastatin Atorvastatin Characteristics 10
mg (N 5006) 80 mg (N 4995) Age
(yr) 60.98.8 61.28.8 Male sex
() 80.8 81.2 White race () 94.1 94.1 Systolic
BP (mm Hg) 13117 13117 Diastolic BP (mm
Hg) 7810 7810 BMI (kg/m2) 28.64.7 28.44.5
LaRosa JC et al. N Engl J Med. 2005352.
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TNT CV history of participants
Atorvastatin Atorvastatin 10 mg (N
5006) 80 mg (N 4995) Current
smoker 13.4 13.4 Former smoker 63.3 63.2 Systemic
hypertension 54.4 53.9 Diabetes
mellitus 15.0 15.0 MI 57.7 59.0 Angina 81.2 81.8 C
erebrovascular event 5.3 5.1 PAD 11.4 12.1 CHF 8.1
7.6 Arrhythmia 18.5 18.2 Coronary
revascularization Angioplasty 54.3 53.8
Bypass 46.7 46.4
LaRosa JC et al. N Engl J Med. 2005352.
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TNT Baseline lipids
Atorvastatin Atorvastatin Lipids (mg/dL) 10
mg (N 5006) 80 mg (N 4995) LDL
cholesterol 9818 9718 Total cholesterol 17524
17524 Triglycerides 15172 15172 HDL
cholesterol 4711 4711
LaRosa JC et al. N Engl J Med. 2005352.
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TNT Treatment effects on LDL-C
160
140
Atorvastatin 10 mg
120
100
LDL-C (mg/dL)
80
60
Atorvastatin 80 mg
40
20
0
Screening
Final
60
48
36
24
3
0
12
Months
LaRosa JC et al. N Engl J Med. 2005352.
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TNT Treatment effects on primary outcome
0.15
Atorvastatin 10 mg
22 risk reduction
0.10
Major CV events ()
0.05
Atorvastatin 80 mg
0.00
6
5
4
2
1
3
0
Years
HR 0.78 (0.690.89) P lt 0.001
LaRosa JC et al. N Engl J Med. 2005352.
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TNT Treatment effects on first major coronary
event

• CHD death, MI, resuscitation after cardiac arrest

0.10
Atorvastatin 10 mg
20 risk reduction
Major CV events ()
0.05
Atorvastatin 80 mg
0.00
6
5
4
2
1
3
0
Years
HR 0.80 (0.690.92) P 0.002
LaRosa JC et al. N Engl J Med. 2005352.
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TNT Treatment effects on CHD death, MI
Atorvastatin 10 mg
0.10
22 risk reduction
Major CV events ()
0.05
Atorvastatin 80 mg
0.00
6
5
4
2
1
3
0
Years
HR 0.78 (0.680.91) P lt 0.001
LaRosa JC et al. N Engl J Med. 2005352.
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TNT Treatment effects on stroke
0.04
Atorvastatin 10 mg
0.03
25 risk reduction
Major CV events ()
0.02
0.01
Atorvastatin 80 mg
0.00
6
5
4
2
1
3
0
Years
HR 0.75 (0. 590.96) P 0.02
LaRosa JC et al. N Engl J Med. 2005352.
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TNT Non-CV mortality
Atorvastatin Atorvastatin 10 mg 80
mg Hazard ratio (N 5006) (N 4995) (95
CI) P Cancer 1.5 1.7 1.13 (0.83, 1.55) 0.42 Other
nontraumatic causes 0.9 1.2 1.35 (0.91,
2.00) 0.13
LaRosa JC et al. N Engl J Med. 2005352.
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TNT Tolerability of treatments
Atorvastatin Atorvastatin 10 mg 80 mg
(N 5006) (N 4995) P Adverse
events 5.8 8.1 lt0.001 Discontinuation 5.3 7.2
lt0.001 Myalgia 4.7 4.8 0.72 ALT/AST gt3x
ULN 0.2 1.2 lt0.001
LaRosa JC et al. N Engl J Med. 2005352.
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TNT Extending and confirming benefit of LDL-C
lowering beyond current guidelines
Event()
LaRosa JC et al. N Engl J Med. 2005352.