Transcript TNT (16 slides

VBWG
VBWG
TNT: New data on
intensive lipid lowering
in stable CHD patients
TNT: Treating to New Targets
VBWG
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:
Atorvastatin 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. 2005;352.
VBWG
Benefit of intensive LDL-C lowering:
Accumulating evidence
30
Statin
25
Placebo
4S
4S
20
Event
(%)
15
LIPID
LIPID
CARE
10
HPS
CARE
HPS
5
0
0
70
90
110 130 150 170
LDL cholesterol (mg/dL)
190
210
LaRosa JC et al. N Engl J Med. 2005;352.
VBWG
TNT: Design
Patient population



250 centers
in 14 countries
(N = 10,001)
LDL 130–250 mg/dL
TG <600 mg/dL
Atorvastatin 10 mg
Atorvastatin 10 mg
Atorvastatin 80 mg
8 weeks
4.9 years
Waters DD et al. Am J Cardiol. 2004;93:154-8.
VBWG
TNT: Baseline characteristics
Atorvastatin
10 mg (N = 5006)
Atorvastatin
80 mg (N = 4995)
60.9±8.8
61.2±8.8
Male sex (%)
80.8
81.2
White race (%)
94.1
94.1
Systolic BP (mm Hg)
131±17
131±17
Diastolic BP (mm Hg)
78±10
78±10
28.6±4.7
28.4±4.5
Characteristics
Age (yr)
BMI (kg/m2)
LaRosa JC et al. N Engl J Med. 2005;352.
VBWG
TNT: CV history of participants
Current smoker
Former smoker
Systemic hypertension
Diabetes mellitus
MI
Angina
Cerebrovascular event
PAD
CHF
Arrhythmia
Coronary revascularization
Angioplasty
Bypass
% Atorvastatin
10 mg (N = 5006)
% Atorvastatin
80 mg (N = 4995)
13.4
63.3
54.4
15.0
57.7
81.2
5.3
11.4
8.1
18.5
13.4
63.2
53.9
15.0
59.0
81.8
5.1
12.1
7.6
18.2
54.3
46.7
53.8
46.4
LaRosa JC et al. N Engl J Med. 2005;352.
VBWG
TNT: Baseline lipids
Lipids (mg/dL)
Atorvastatin
Atorvastatin
10 mg (N = 5006) 80 mg (N = 4995)
LDL cholesterol
98±18
97±18
Total cholesterol
175±24
175±24
Triglycerides
151±72
151±72
47±11
47±11
HDL cholesterol
LaRosa JC et al. N Engl J Med. 2005;352.
VBWG
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 0
3
12
24
36
48
60
Final
Months
LaRosa JC et al. N Engl J Med. 2005;352.
VBWG
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
0
1
2
3
4
5
6
Years
HR = 0.78 (0.69–0.89)
P < 0.001
LaRosa JC et al. N Engl J Med. 2005;352.
VBWG
TNT: Treatment effects on first major
coronary event
CHD death, MI, resuscitation after cardiac arrest
0.10
Major CV
events (%)
20% risk
reduction
Atorvastatin 10 mg
0.05
Atorvastatin 80 mg
0.00
0
HR = 0.80 (0.69–0.92)
P = 0.002
1
2
3
Years
4
5
6
LaRosa JC et al. N Engl J Med. 2005;352.
VBWG
TNT: Treatment effects on CHD death, MI
Atorvastatin 10 mg
0.10
Major CV
events (%)
22% risk
reduction
0.05
Atorvastatin 80 mg
0.00
0
HR = 0.78 (0.68–0.91)
P < 0.001
1
2
3
Years
4
5
6
LaRosa JC et al. N Engl J Med. 2005;352.
VBWG
TNT: Treatment effects on stroke
0.04
Atorvastatin 10 mg
0.03
Major CV
events (%)
25% risk
reduction
0.02
0.01
Atorvastatin 80 mg
0.00
0
HR = 0.75 (0. 59–0.96)
P = 0.02
1
2
3
Years
4
5
6
LaRosa JC et al. N Engl J Med. 2005;352.
VBWG
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. 2005;352.
VBWG
TNT: Tolerability of treatments
% Atorvastatin % Atorvastatin
10 mg
80 mg
(N = 5006)
(N = 4995)
P
Adverse events
5.8
8.1
<0.001
Discontinuation
5.3
7.2
<0.001
Myalgia
4.7
4.8
0.72
ALT/AST >3x ULN
0.2
1.2
<0.001
LaRosa JC et al. N Engl J Med. 2005;352.
VBWG
TNT: Extending and confirming benefit of
LDL-C lowering beyond current guidelines
30
Statin
25
Placebo
4S
4S
20
Event
(%)
15
LIPID
LIPID
CARE
10
HPS
5
CARE
HPS
TNT (10 mg atorvastatin)
TNT (80 mg atorvastatin)
0
0
70
90
110 130 150 170
LDL cholesterol (mg/dL)
190
210
LaRosa JC et al. N Engl J Med. 2005;352.