Impact of Triglyceride Levels Beyond
Low-Density Lipoprotein Cholesterol
After Acute Coronary Syndrome in
the PROVE IT-TIMI 22 Trial
Michael Miller MD, FACC, Christopher P. Cannon
MD FACC, Sabina A. Murphy MPH, Jie Qin MS,
Kausik K. Ray MD, Eugene Braunwald MD, MACC
for the PROVE IT-TIMI 22 Investigators
Miller et al. J Am Coll Cardiol 2008;51:1724-30
Copyright ©2008 American College of Cardiology Foundation. Restrictions may apply.
Background and Objectives


The PROVE IT-TIMI 22 trial demonstrated that LDL-C < 70
mg/dL was associated with greater CHD event reduction than
LDL-C <100 mg/dL after ACS.
We evaluated the impact of TG in the PROVE IT-TIMI 22 trial,
reasoning that if high LDL-C and TG increases CHD risk more
than isolated high LDL-C, then the combination of low ontreatment LDL-C and TG would be associated with reduced
CHD risk compared to low LDL-C (< 70 mg/dL) alone.
Miller et al. J Am Coll Cardiol 2008;51:1724-30
Copyright ©2008 American College of Cardiology Foundation. Restrictions may apply
Methods


Study Population:
4,162 patients in The Pravastatin or Atorvastatin
Evaluation and Infection Therapy-Thrombolysis In
Myocardial Infarction 22 (PROVE IT-TIMI 22) trial
Blood Sampling:
Plasma samples for lipids, lipoproteins, HS-CRP at baseline,
30 d, and 4, 8, 16, 24 months
Composite Endpoint:
Death, myocardial infarction (MI) or recurrent ACS
between 30 d and 2 yr follow-up
Miller et al. J Am Coll Cardiol 2008;51:1724-30
Copyright ©2008 American College of Cardiology Foundation. Restrictions may apply.
Methods (2)
Statistical Analysis
Kaplan-Meier event rates after censoring events
within 30 days of initial ACS event.
Cox proportional hazards model:
Age, gender, DM, HTN, obesity (BMI > 30 kg/m2),
cigarette smoking (active), low HDL-C to estimate
effect of on-treatment LDL-C (70 mg/dL) and TG (150 mg/dL) within 30
days or 4 months of initial ACS event.
CRP (2 mg/L) included to assess triple goal attainment
Miller et al. J Am Coll Cardiol 2008;51:1724-30
Copyright ©2008 American College of Cardiology Foundation. Restrictions may apply.
Results
0.20
0.20
Kaplan-Meier Estimates Based on LDL-C < 70 mg/dL or
TG < 150 mg/dL Between 30 days and 2 yr Follow-Up
HR: 0.73 (0.62, 0.87)
LDL ≥ 70
TG ≥ 150
0.15
P < 0.001
0.10
0.10
0.15
HR: 0.81 (0.68, 0.96)
P = 0.015
TG < 150
0.00
0.00
0.05
0.05
LDL < 70
0
150
330
510
Days After Month 1 Visit
700
0
150
330
510
700
Days After Month 1 Visit
Miller et al. J Am Coll Cardiol 2008;51:1724-30
Copyright ©2008 American College of Cardiology Foundation. Restrictions may apply.
Results
Rate of Death, MI or Recurrent
ACS after 30 days
Hazard of Death, MI & Recurrent ACS with on-treatment
LDL-C (70 mg/dL) & TG (150 mg/dL)
Ref
17.9%
P = 0.180
20.0%
P = 0.192
15.0%
16.5%
15.0%
P = 0.017
HR: 0.85
11.7%
(0.67-1.08)
10.0%
HR: 0.72
HR: 0.84
(0.54-0.94)
(0.65-1.09)
5.0%
0.0%
LDL-C ≥ 70
LDL-C < 70
TG < 150
TG ≥ 150
Adjusted for age, sex, smoking, DM, HTN, obesity, HDL, PVD, prior ACS, prior statin use and treatment effect
Miller et al. J Am Coll Cardiol 2008;51:1724-30
Copyright ©2008 American College of Cardiology Foundation. Restrictions may apply.
Results
Proportion of Pravastatin (40 mg) and Atorvastatin (80 mg)
Treated Patients Attaining LDL-C < 70, CRP < 2 & TG < 150 at 30 days
100
* P < 0.0001 between the treatment groups
80
35%*
60
40
Pravastatin
Atorvastatin
6.6%
20
0
Triple Goal
Miller et al. J Am Coll Cardiol 2008;51:1724-30
Copyright ©2008 American College of Cardiology Foundation. Restrictions may apply.
Results
Hazard of death, MI or
Recurrent ACS after 30 days
Hazard of death, MI and recurrent ACS with number of goals
achieved based on LDL-C < 70, CRP < 2 & TG < 150 mg/dL at 30 d
P=0.017
1
P= 0.007
0.72
0.8
0.6
0.68
0.56-0.94
35%*
P= 0.002
0.59
0.52-0.90
6.6%
0.4
0.41-0.83
0.2
0
1
2
3
Number of Goals Achieved
Adjusted for age, sex, smoking, DM, HTN, obesity, HDL, PVD, prior ACS, prior statin use and treatment effect
Miller et al. J Am Coll Cardiol 2008;51:1724-30
Copyright ©2008 American College of Cardiology Foundation. Restrictions may apply.
Conclusions
On-treatment TG < 150 mg/dL was associated
with a lower risk of recurrent CHD events
independently of the level of LDL-C.
Therefore, these data lend support to the
concept that achieving both a low LDL-C and
low TG may be important therapeutic
parameters following ACS
Miller et al. J Am Coll Cardiol 2008;51:1724-30
Copyright ©2008 American College of Cardiology Foundation. Restrictions may apply.