1. 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:
Copyright ©2008 American College of Cardiology Foundation. Restrictions may apply.

2. 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 on-treatment 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:
Copyright ©2008 American College of Cardiology Foundation. Restrictions may apply

3. Methods Study Population: Blood Sampling: Composite Endpoint:
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:
Copyright ©2008 American College of Cardiology Foundation. Restrictions may apply.

4. 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:
Copyright ©2008 American College of Cardiology Foundation. Restrictions may apply.

5. Results
Kaplan-Meier Estimates Based on LDL-C < 70 mg/dL or TG < 150 mg/dL Between 30 days and 2 yr Follow-Up
0.00
0.05
0.10
0.15
0.20
150
330
510
700
Days After Month 1 Visit
TG < 150
TG ≥ 150
HR: 0.73 (0.62, 0.87)
P < 0.001
Days After Month 1 Visit
LDL < 70
LDL ≥ 70
HR: 0.81 (0.68, 0.96)
P = 0.015
Kaplan-Meier estimates of death, MI and recurrent ACS
between 30 days and 2 years of follow-up based on a) achieved LDL-C < 70 mg/dL and b) TG < 150 mg/dL.
Miller et al. J Am Coll Cardiol 2008;51:
Copyright ©2008 American College of Cardiology Foundation. Restrictions may apply. 5

6. Rate of Death, MI or Recurrent ACS after 30 days
Results
TG < 150
TG ≥ 150
LDL-C < 70
LDL-C ≥ 70
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
P = 0.192
15.0%
16.5%
P = 0.017
HR: 0.85
( )
11.7%
HR: 0.72
( )
HR: 0.84
( )
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:
Copyright ©2008 American College of Cardiology Foundation. Restrictions may apply. 6

7. Results Proportion of Pravastatin (40 mg) and Atorvastatin (80 mg) Treated Patients Attaining LDL-C < 70, CRP < 2 & TG < 150 at 30 days
* P < between the treatment groups
35%*
6.6%
Proportion of on-treatment
Percentage of TG reduction (mean and median) and proportion of Atorvastatin and Pravastatin treated patients attaining LDL-C < 70 mg/dL or TG < 150 mg/dL, the dual goals of LDL-C <70 mg/dL and TG <150 mg/dL or the triple goal of LDL-C<70 mg/dL, CRP < 2 mg/L and TG < 150 mg/dL at 30 days or 4 months after ACS.
At 30 days Atorvastatin 34.5%, Pravastatin 6.6%
Miller et al. J Am Coll Cardiol 2008;51:
Copyright ©2008 American College of Cardiology Foundation. Restrictions may apply.

8. Results 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
35%*
6.6%
Percentage of TG reduction (mean and median) and proportion of Atorvastatin and Pravastatin treated patients attaining LDL-C < 70 mg/dL or TG < 150 mg/dL, the dual goals of LDL-C <70 mg/dL and TG <150 mg/dL or the triple goal of LDL-C<70 mg/dL, CRP < 2 mg/L and TG < 150 mg/dL at 30 days or 4 months after ACS.
At 30 days Atorvastatin 34.5%, Pravastatin 6.6%
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:
Copyright ©2008 American College of Cardiology Foundation. Restrictions may apply.

9. 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:
Copyright ©2008 American College of Cardiology Foundation. Restrictions may apply.