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When it comes to outcomes, metabolic syndrome is no more than a sum of its parts, according to a substudy of the COURAGE trial published in the July 5, 2011, issue of the Journal of the American College of Cardiology. In addition to finding that the risk of death and myocardial infarction (MI) is mediated by the components of metabolic syndrome rather than the diagnosis as a whole, the analysis observed that percutaneous coronary intervention (PCI) holds no benefit over optimal medical therapy alone regardless of whether patients have metabolic syndrome or diabetes.

The original COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial evaluated optimal medical therapy with or without PCI in patients with stable coronary artery disease (CAD). Results published in the New England Journal of Medicine in 2007 indicated that death and MI rates were equal in the 2 treatment arms.

For the current substudy, David J. Maron, MD, of Vanderbilt University School of Medicine (Nashville, TN), and colleagues conducted a post hoc analysis that divided 2,248 patients from the COURAGE trial into 4 groups:

• Group A (n = 765) had neither metabolic syndrome nor diabetes
• Group B (n = 717) had metabolic syndrome but not diabetes
• Group C (n = 121) had diabetes but not metabolic syndrome
• Group D (n = 645) had both metabolic syndrome and diabetes

Dr. Maron and colleagues looked at the effect of PCI within each group, and they also calculated the degree to which 5 components of metabolic syndrome—including hypertension, low HDL cholesterol, elevated glucose/diabetes, elevated triglycerides, and obesity—predicted adverse outcomes and whether the presence of metabolic syndrome itself had independent prognostic significance beyond its individual parts.

Overall, 61% of the patients had metabolic syndrome and 34% had diabetes. After a median follow-up period of 4.6 years, the risk of death or MI increased steadily across varying levels of disease, from 14% in Group A to 25% in Group D (P < 0.01). While the presence of metabolic syndrome was linked with a significantly increased risk, this association disappeared after adjusting for the syndrome’s 5 components (HR 1.15; 95% CI 0.79-1.68; P = 0.46).

Among the various components, the strongest predictors of MI or death were hypertension, low HDL cholesterol, and elevated glucose (table 1).

Table 1. Predictors of Death/MI

Whether patients were allocated to undergo primary PCI did not influence the risk of death or MI in any of the 4 subgroups.

Metabolic Syndrome as Marker of Risk

While the study indicates that identifying metabolic syndrome offers no additional prognostic value over its component parts, Dr. Maron told TCTMD in an e-mail correspondence that, “the identification of metabolic syndrome may help clinicians recognize patients at increased risk who may not be recognized as such by current guidelines.

“For example, the blood pressure and glucose thresholds used to define metabolic syndrome are lower than guideline-recommended thresholds for pharmacological treatment of these risk factors,” he said. “So the identification of metabolic syndrome in patients not meeting established treatment criteria for lipids, glucose, or blood pressure should trigger lifestyle interventions focused on physical activity, diet, and weight loss.”

Dr. Maron added that even among stable CAD patients, particularly those with diabetes, “metabolic syndrome identifies patients at increased risk for death or MI. [They] deserve intensive medical therapy with lifestyle counseling and medication to control the individual risk factors that constitute that risk.”

Management Remains a Challenge

In a telephone interview with TCTMD, Sorin J. Brener, MD, of Weill Cornell Medical College (New York, NY), highlighted how difficult it can be to manage patients with metabolic syndrome.

The COURAGE trial “was very successful in treating all of these components, with the exception of obesity, which they didn’t manage to lower. This is very different from reality. In real life, we are much, much less successful,” Dr. Brener said, noting that the accompanying editorial by Thomas E. Kottke, MD, of HealthPartners (Minneapolis, MN), points out that “enormous resources” would need to be expended to match the trial’s outcomes.

Dr. Maron agreed, saying, “It is clear that we need more effective methods to prevent and treat the individual components of metabolic syndrome.”

Aim for Optimal Medical Therapy

In his editorial, Dr. Kottke offers some guidance. “Failure to adhere to goal lifestyle and medication regimens in the long term is a significant problem for patients with CAD,” he writes. “However, the use of disease-management tools increases adherence, and 2 tools have been designed specifically for use by cardiologists: the AHA program Get With the Guidelines-Outpatient and the [American College of Cardiology’s] Practice Innovation and Clinical Excellence (PINNACLE) registry. These management tools can help cardiologists increase the value of their services by improving outcomes and increasing the effectiveness and efficiency of care.”

Regarding the lack of benefit for primary PCI, Michael E. Farkouh, MD, of Mount Sinai School of Medicine (New York, NY), commented in a telephone interview with TCTMD that these findings are “a striking reminder that the therapies that we study in clinical trials do have an enduring effect on patients.”

Importantly, optimal medical therapy appears effective in this population, he said. “Some of these patients down the road will require PCI, but when faced with patients with stable coronary disease who have metabolic syndrome or diabetes, start with optimal medical therapy first.”

 

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Sources:
1. Maron DJ, Boden WE, John A. Spertus JA, et al. Impact of metabolic syndrome and diabetes on prognosis and outcomes with early percutaneous coronary intervention in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial. J Am Coll Cardiol. 2011;58:131-137.

2. Kottke TE. The lessons of COURAGE for the management of stable coronary artery disease. J Am Coll Cardiol. 2011;58:138-139.

 

 

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