VBWG

VBWG

TNT: New data on

intensive lipid lowering
in stable CHD patients
 VBWG
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: 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 4S

Placebo
25
4S
20
Event
(%) 15 LIPID LIPID
CARE
CARE
10 HPS
HPS

0
0 70 90 110 130 150 170 190 210
LDL cholesterol (mg/dL)
LaRosa JC et al. N Engl J Med. 2005;352.
 VBWG
TNT: Design

Patient population
Atorvastatin 10 mg

 250 centers Atorvastatin 10 mg

in 14 countries Atorvastatin 80 mg
(N = 10,001)
 LDL 130–250 mg/dL
8 weeks 4.9 years
 TG <600 mg/dL

Waters DD et al. Am J Cardiol. 2004;93:154-8.

 VBWG
TNT: Baseline characteristics

Atorvastatin Atorvastatin
Characteristics 10 mg (N = 5006) 80 mg (N = 4995)

Age (yr) 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

BMI (kg/m2) 28.6±4.7 28.4±4.5

LaRosa JC et al. N Engl J Med. 2005;352.

 VBWG
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
Cerebrovascular 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. 2005;352.
 VBWG
TNT: Baseline lipids

Atorvastatin Atorvastatin
Lipids (mg/dL) 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

HDL cholesterol 47±11 47±11

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
80
(mg/dL)
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
0.10 reduction
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 Atorvastatin 10 mg
20% risk
reduction

Major CV
events (%) 0.05
Atorvastatin 80 mg

0.00
0 1 2 3 4 5 6
Years
HR = 0.80 (0.69–0.92)
P = 0.002 LaRosa JC et al. N Engl J Med. 2005;352.
 VBWG
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
0 1 2 3 4 5 6
Years

HR = 0.78 (0.68–0.91)
P < 0.001 LaRosa JC et al. N Engl J Med. 2005;352.
 VBWG
TNT: Treatment effects on stroke

0.04

Atorvastatin 10 mg
0.03
25% risk
Major CV reduction
events (%) 0.02

0.01
Atorvastatin 80 mg
0.00
0 1 2 3 4 5 6
Years

HR = 0.75 (0. 59–0.96)

P = 0.02 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 4S

Placebo
25
4S
20
Event
15 LIPID LIPID
(%)
CARE CARE
10 HPS HPS
TNT (10 mg atorvastatin)
5 TNT (80 mg atorvastatin)

0
0 70 90 110 130 150 170 190 210
LDL cholesterol (mg/dL)
LaRosa JC et al. N Engl J Med. 2005;352.