Patients with coronary heart disease (CHD) are at a much higher risk of a major cardiovascular (CV) event if they also have the metabolic syndrome, based on a new study that also showed that this increased risk could be significantly reduced with intensive lipid-lowering therapy (Lancet. 2006; 368:919-928).

This post hoc analysis of the TNT (Treating to New Targets) study, in which 10,000 patients with CHD  (ages, 25-75 years) were randomly assigned to atorvastatin (Lipitor) 10 mg or 80 mg and then followed for 5 years, examined the effects of reducing low-density lipoprotein cholesterol (LDL-C) in patients with the metabolic syndrome. 

“Strikingly, over half of the patients in the TNT study met the current clinical criteria for a diagnosis of the metabolic syndrome,” note the authors of this study, led by Prakash Deedwania, of the University of California San Francisco School of Medicine.

Among those with the metabolic syndrome, 2820 received the 10-mg dose and 2764 received the 80-mg dose. Regardless of treatment assignment, patients with CHD and the metabolic syndrome were significantly more likely to have a major CV event than were those who did not have the metabolic syndrome at the end of 5 years.

This increased risk was significantly lower among the CHD/metabolic syndrome patients who were treated with intensive LDL-C–lowering therapy. Some 13% of those in the atorvastatin 10-mg group had a primary major CV event (ie, death from CHD, nonfatal nonprocedure-related myocardial infarction, resuscitated cardiac arrest, or fatal or nonfatal stroke), compared with only 9.5% of those in the 80-mg group. The higher-dose group also had a lower incidence of the secondary outcomes (Figure).

After excluding patients with diabetes, patients with CHD and the metabolic syndrome had a 35% higher risk of CV events than those without the metabolic syndrome. But the 80-mg dose of atorvastatin reduced the incidence of a major CV event by 29% in this cohort when compared with the 10-mg dose.

Notably, the incidence of adverse events was similar in both treatment groups, with discontinuation rates of 5.4% with the 10-mg dose and 6.4% with the 80-mg dose.

 “The present analysis justifies classifying patients with coronary heart disease and metabolic syndrome as being at high risk of future cardiovascular events,” the authors write.

They add that these data support the lower LDL-C goal of ≤70 mg/dL now recommended by the National Cholesterol Education Program—a target that would require higher-dose atorvastatin in most patients with CHD and the metabolic syndrome.