Istanbul, Turkey - A study presented this week casts some doubt on the clinical benefit of lowering triglyceride levels in statin-treated patients with stable coronary artery disease. This most recent analysis showed that while elevated plasma triglycerides identified patients at increased risk for recurrence of disease, the association depended on other risk factors, especially HDL cholesterol.

"These data do not imply that lowering of triglycerides by other means necessarily confers clinical benefit," said lead investigator Dr Ole Faergeman (Aarhus Amtssygehus University Hospital, Denmark).

The results, from the Incremental Decrease in Events through Aggressive Lipid Lowering (IDEAL) study, conflict with a recently published analysis of the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE-IT TIMI-22) study. In that analysis, reported by heartwire, investigators showed that low on-treatment triglyceride levels in post- ACS patients was associated with a lower risk of recurrent coronary events, even after adjustment by other covariates.

Faergeman, who presented the IDEAL results at the 77th European Atherosclerosis Society Congress, pointed out that guidelines identify high plasma triglycerides as markers of risk of cardiovascular disease, but the National Cholesterol Education Program (NCEP) guidelines do not have a target goal for patients, although <150 mg/mL, the level used in the classification of the metabolic syndrome, is often applied.

The purpose of this study, he said, was to determine whether triglyceride concentrations were associated with cardiovascular risk in statin-treated patients with stable coronary artery disease. IDEAL, one of the studies that contributed to the push for lowering LDL-cholesterol levels beyond then-recommended targets, was first presented in 2005 and included 8888 patients aged 80 years or younger with a history of acute MI treated with atorvastatin (Lipitor, Pfizer) 80 mg or usual-dose simvastatin (Zocor, Merck).

Presenting the triglyceride analysis, Faergeman showed that on-treatment triglyceride levels <150 mg/dL were associated with a significantly reduced risk of cardiovascular events, even among those with low LDL-cholesterol levels. In an analysis adjusted for age and sex, even slightly elevated triglyceride levels, those between 80 and 99 mg/dL, identified patients with increased risk for any recurrent cardiovascular event. However, this association was no longer significant in a multivariate analysis, especially after adjustment for HDL cholesterol and the apolipoprotein B/apolipoprotein A1 ratio.

Speculating as to why there was a benefit observed with lowered triglycerides in PROVE-IT but not IDEAL, Faergeman said the studies included different patient populations, and it is likely that stable coronary patients might not benefit as much from lowered triglycerides as post-ACS patients. Moreover, the PROVE-IT investigators looked at the association between cardiovascular events and triglyceride levels from one month until two years, while IDEAL analyzed the data from 12 months to five years. This different period of observation could have also affected the results, he said.

In terms of a clinical message, at the present time, he said, there are very limited data from clinical trials to document that lowering triglycerides lowers the risk of coronary heart disease.