Coronary artery disease
Plasma Triglycerides and Cardiovascular Events in the Treating to New Targets and Incremental Decrease in End-Points Through Aggressive Lipid Lowering Trials of Statins in Patients With Coronary Artery Disease

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We determined the ability of in-trial measurements of triglycerides (TGs) to predict new cardiovascular events (CVEs) using data from the Incremental Decrease in End Points through Aggressive Lipid Lowering (IDEAL) and Treating to New Targets (TNT) trials. The trials compared atorvastatin 80 mg/day with moderate-dose statin therapy (simvastatin 20 to 40 mg/day in IDEAL and atorvastatin 10 mg/day in TNT) in patients with clinically evident coronary heart disease or a history of myocardial infarction. The outcome measurement in the present research was CVE occurring after the first year of the trial. After adjusting for age, gender, and study, risk of CVEs increased with increasing TGs (p <0.001 for trend across quintiles of TGs). Patients in the highest quintile had a 63% higher rate of CVEs than patients in the lowest quintile (hazard ratio 1.63, 95% confidence interval 1.46 to 1.81) and the relation of TGs to risk was apparent even within the normal range of TGs. The ability of TG measurements to predict risk decreased when high-density lipoprotein cholesterol and apolipoprotein B:apolipoprotein A-1 were included in the statistical analysis, and it was abolished with inclusion of further variables (diabetes, body mass index, glucose, hypertension, and smoking; (p = 0.044 and 0.621, respectively, for trend across quintiles of TGs). Similar results were obtained in patients in whom low-density lipoprotein cholesterol had been lowered to guideline-recommended levels. In conclusion, even slightly increased TG levels are associated with higher risk of recurrence of CVEs in statin-treated patients and should be considered a useful marker of risk.

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Methods

The study designs and primary results of the IDEAL and TNT trials have been published.1, 2, 3, 4 TNT was a prospective, double-blind, parallel-group trial with a median follow-up of 4.9 years. IDEAL was a prospective, randomized, open-label, blinded end-point evaluation trial with a median follow-up of 4.8 years. In TNT, 10,001 patients 35 to 75 years of age with clinically evident coronary heart disease and plasma concentrations of low-density lipoprotein (LDL) cholesterol <130 mg/dl (3.4

Results

One year into the trials, 7,232 of 8,888 patients in IDEAL (81.4%) and 8,547 of 10,001 patients in TNT (85.5%) had complete lipid assessments and were eligible for inclusion in the TG analysis. Baseline characteristics and study measurements of lipoprotein variables 1 year into the trials are listed in Table 1. Note that, due to study treatment, LDL cholesterol and apoB were low in the 2 trials.

Data displayed in Figure 1 show that risk of a CVE was higher in patients with TGs >150 than <150

Discussion

The main finding of this post hoc analysis of data from 2 large trials of statin-treated patients was that measurements of plasma TGs allow us to differentiate between levels of risk of recurrence of CVEs, even in patients who have been treated to recommended goals for lowering LDL cholesterol. These results are consistent with those of the Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial10; however, unlike that

Acknowledgment

Editorial and graphical support was provided by Paul Lane and Richard Threlfall at UBC Scientific Solutions, Ltd., Horsham, West Sussex, United Kingdom.

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The IDEAL and TNT studies were sponsored by Pfizer, Inc., New York, New York.

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