Author + information
- Received March 1, 2015
- Revision received March 10, 2015
- Accepted March 17, 2015
- Published online June 2, 2015.
- Gregory G. Schwartz, MD, PhD∗∗ (, )
- Markus Abt, PhD†,
- Weihang Bao, PhD‡,
- David DeMicco, PharmD‡,
- David Kallend, MD†,
- Michael Miller, MD§,
- Hardi Mundl, MD† and
- Anders G. Olsson, MD, PhD‖,¶
- ∗Cardiology Section, VA Medical Center and University of Colorado School of Medicine, Denver, Colorado
- †Pharma Development, F. Hoffmann-La Roche, Basel, Switzerland
- ‡Pfizer, Inc., New York, New York
- §Division of Cardiovascular Medicine, University of Maryland School of Medicine, Baltimore, Maryland
- ‖Stockholm Heart Center, Stockholm, Sweden
- ¶University of Linköping, Linköping, Sweden
- ↵∗Reprint requests and correspondence:
Dr. Gregory G. Schwartz, Cardiology Section 111B, Denver VA Medical Center, 1055 Clermont Street, Denver, Colorado 80220.
Background Most patients with acute coronary syndrome (ACS) are treated with statins, which reduce atherogenic triglyceride-rich lipoproteins. It is uncertain whether triglycerides predict risk after ACS on a background of statin treatment.
Objectives This study examined the relationship of fasting triglyceride levels to outcomes after ACS in patients treated with statins.
Methods Long-term and short-term relationships of triglycerides to risk after ACS were examined in the dal-OUTCOMES trial and atorvastatin arm of the MIRACL (Myocardial Ischemia Reduction with Acute Cholesterol Lowering) trial, respectively. Analysis of dal-OUTCOMES included 15,817 patients (97% statin-treated) randomly assigned 4 to 12 weeks after ACS to treatment with dalcetrapib (a cholesteryl ester transfer protein inhibitor) or placebo and followed for a median 31 months. Analysis of MIRACL included 1,501 patients treated with atorvastatin 80 mg daily beginning 1 to 4 days after ACS and followed for 16 weeks. Fasting triglycerides at initial random assignment were related to risk of coronary heart disease death, nonfatal myocardial infarction, stroke, and unstable angina in models adjusted for age, sex, hypertension, smoking, diabetes, high-density lipoprotein cholesterol, and body mass index.
Results Fasting triglyceride levels were associated with both long-term and short-term risk after ACS. In dal-OUTCOMES, long-term risk increased across quintiles of baseline triglycerides (p < 0.001). The hazard ratio in the highest/lowest quintile (>175/≤80 mg/dl) was 1.61 (95% confidence interval: 1.34-1.94). There was no interaction of triglycerides and treatment assignment on the primary outcome. In the atorvastatin group of MIRACL, short-term risk increased across tertiles of baseline triglycerides (p = 0.03), with a hazard ratio of 1.50 (95% confidence interval: 1.05 to 2.15) in highest/lowest tertiles (>195/≤135 mg/dl). The relationship of triglycerides to risk was independent of low-density lipoprotein cholesterol in both studies.
Conclusions Among patients with ACS treated effectively with statins, fasting triglycerides predict long-term and short-term cardiovascular risk. Triglyceride-rich lipoproteins may be an important additional target for therapy. (A Study of RO4607381 in Stable Coronary Heart Disease Patients With Recent Acute Coronary Syndrome; NCT00658515)
The dal-OUTCOMES trial was funded by F. Hoffmann-La Roche Ltd. The MIRACL trial was funded by Pfizer. Dr. Schwartz, through his institution, has received research grants from Anthera, Pfizer, Resverlogix, Roche, and Sanofi. Dr. Abt is an employee of F. Hoffmann-La Roche, Ltd. Drs. Bao and DeMicco are employees of Pfizer. Drs. Kallend and Mundl were employees of F. Hoffmann-La Roche at the time the dal-OUTCOMES study was performed and data collected. Dr. Miller has served as a consultant for Amarin, AstraZeneca, Pronova, and Zydus. Dr. Olsson has received research grants from Amgen, AstraZeneca, Karobio, Merck, Pfizer, Roche, and Sanofi; and has received consultation fees from AstraZeneca, Karobio, Merck, Pfizer, and Roche. Dr. Kallend is currently affiliated with The Medicines Company, Zurich, Switzerland. Dr. Mundl is currently affiliated with Bayer Pharmaceuticals, Berlin, Germany.
Portions of this work have been previously presented in abstract form (American College of Cardiology 63rd Scientific Sessions; J Am Coll Cardiol 2014;63 Suppl A:A63).
- Received March 1, 2015.
- Revision received March 10, 2015.
- Accepted March 17, 2015.
- American College of Cardiology Foundation