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CLINICAL RESEARCH: LIPIDS AND CAD

Impact of Triglyceride Levels Beyond Low-Density Lipoprotein Cholesterol After Acute Coronary Syndrome in the PROVE IT-TIMI 22 Trial

Michael Miller, MD, FACC^_*,1,_*, Christopher P. Cannon, MD, FACC^,2, Sabina A. Murphy, MPH, Jie Qin, MS, Kausik K. Ray, MD, MRCP^,3, Eugene Braunwald, MD, MACC^,4 for the PROVE IT-TIMI 22 Investigators

^_* University of Maryland Medical Center, Baltimore, Maryland
TIMI Study Group, Brigham and Women’s Hospital, Boston, Massachusetts
University of Cambridge, Cambridge, United Kingdom.

Manuscript received August 21, 2007; revised manuscript received October 18, 2007, accepted October 22, 2007.

^_* Reprint requests and correspondence: Dr. Michael Miller, University of Maryland Hospital, Division of Cardiology, Room S3B06, 22 South Greene Street, Baltimore, Maryland 21201. (Email: mmiller{at}heart.umaryland.edu).

Objectives: The purpose of this study was to assess the impact of on-treatment triglycerides (TG) on coronary heart disease (CHD) risk after an acute coronary syndrome (ACS).

Background: The PROVE IT-TIMI (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction) 22 trial demonstrated that low-density lipoprotein cholesterol (LDL-C) <70 mg/dl was associated with greater CHD event reduction than LDL-C <100 mg/dl after ACS. However, the impact of low on-treatment TG on CHD risk beyond LDL-C <70 mg/dl has not been explored.

Methods: The PROVE IT-TIMI 22 trial evaluated 4,162 patients hospitalized for ACS and randomized to atorvastatin 80 mg or pravastatin 40 mg daily. The relationship between on-treatment levels of TG and LDL-C and the composite end point of death, myocardial infarction (MI), and recurrent ACS were assessed 30 days after initial presentation.

Results: Low on-treatment TG (<150 mg/dl) was associated with reduced CHD risk compared with higher TG in univariate analysis (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.62 to 0.87; p < 0.001) and in adjusted analysis (HR 0.80, 95% CI 0.66 to 0.97; p = 0.025). For each 10-mg/dl decrement in on-treatment TG, the incidence of death, MI, and recurrent ACS was lower by 1.6% or 1.4% after adjustment for LDL-C or non–high-density lipoprotein cholesterol and other covariates (p < 0.001 and p = 0.01, respectively). Lower CHD risk was also observed with TG <150 mg/dl and LDL-C <70 mg/dl (HR 0.72, 95% CI 0.54 to 0.94; p = 0.017) or low on-treatment TG, LDL-C, and C-reactive protein (<2 mg/l) (HR 0.59, 95% CI 0.41 to 0.83; p = 0.002) compared with higher levels of each variable in adjusted analysis.

Conclusions: On-treatment TG <150 mg/dl was independently associated with a lower risk of recurrent CHD events, lending support to the concept that achieving low TG may be an additional consideration beyond low LDL-C in patients after ACS. (The PROVE IT-TIMI 22 trial; NCT00382460 [ClinicalTrials.gov] )

Abbreviations and Acronyms   ACS = acute coronary syndrome   CHD = coronary heart disease   CRP = C-reactive protein   HDL-C = high-density lipoprotein cholesterol   LDL-C = low-density lipoprotein cholesterol   MI = myocardial infarction   TG = triglycerides

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JACC 2008 51: 35-36. [Full Text]