FIELD: Fenofibrate reduced CVD risk among patients with type 2 diabetes, metabolic syndrome

Patients with dyslipidemia had the greatest five-year risk for CVD and derived the greatest benefit from fenofibrate treatment.

Patients with type 2 diabetes and metabolic syndrome and thus higher cardiovascular disease risk were likely to reap the greatest benefits of fenofibrate treatment, according to findings from the FIELD study.

The researchers documented the long-term effect of daily fenofibrate on CVD events in patients with type 2 diabetes. They followed 9,795 patients for five years to explore whether CVD event rates were increased in patients with and without various features of the metabolic syndrome.

The majority of the study population had no prior CVD (78.2%; n=7,664) and were men (62.7%; n=6,138). For the patients assigned to fenofibrate, 4,080 had metabolic syndrome and 815 did not. Among the patients assigned to placebo, 4,103 had metabolic syndrome and 797 did not.

Using the National Cholesterol Education Program Adult Treatment Panel III definition of metabolic syndrome, more than 80% of FIELD participants had the condition. Each feature of metabolic syndrome — excluding increased waist circumference — was associated with an increase in absolute five-year risk for CVD events by at least 3%.

“The CVD event rates in the FIELD population with metabolic syndrome and with individual features of metabolic syndrome were significantly higher than in those without metabolic syndrome, indicating that, even in the presence of established type 2 diabetes, metabolic syndrome still confers important additional prognostic information,” the researchers wrote.

Five-year CVD event rates

The absolute benefits of fenofibrate may be greater when metabolic syndrome features are present, as metabolic syndrome components identify higher CVD risk in this patient population, according to the study.

Patients with metabolic syndrome assigned to fenofibrate experienced a five-year CVD risk reduction from 14.5% to 13.1% (adjusted HR=0.89; 95% CI, 0%-21%) and patients without metabolic syndrome experienced a reduction from 11.3% to 9.7% (adjusted HR=0.88; 95% CI, –19% to 35%).

Among patients assigned to placebo, the five-year CVD event rate was 14.5% for patients with metabolic syndrome compared with 11.3% for those who did not meet the criteria (n=1,612; P<.0001). Individuals with any feature of the metabolic syndrome had a CVD event rate similar to that reported in the overall population — it varied from 13.3% for high waist circumference to 15.4% for elevated triglycerides.

Although elevated waist circumference was not associated with increased CVD risk (P=.61), HDL (P=.003), elevated systolic blood pressure and triglycerides (P=.0004) were independent contributors.

Marked dyslipidemia — defined as elevated triglycerides >2.3 mmol/L and low HDL — was associated with the highest risk for CVD events (17.8%). Fenofibrate significantly reduced CVD events in patients with marked dyslipidemia (27% RR reduction; 95% CI, 9%-42%).

Scott R. Diabetes Care. 2009;32:493-498.

This was an interesting study because it showed that more than 80% of FIELD participants qualified for having metabolic syndrome. The researchers found that those who had the really high triglycerides and low HDL were at the highest risk over five years, and those were the individuals who really got the largest benefit of fenofibrate. In the primary prevention setting, patients with marked hypertriglyceridemia experienced the largest decrease in CV events with fenofibrate; in secondary prevention there wasn't nearly as significant a benefit, probably because there was a greater amount of statin drop-in in that group. These findings aren't earth-shattering but support the idea that fenofibrate has the largest effect in patients with higher triglycerides and lower HDL. Our whole field is still waiting for the results from ACCORD, which will be the definitive study to tell us how much added benefit fenofibrate has on top of a statin, and AIM-HIGH, which is looking at the incremental predictive value of extended release niacin on top of statin therapy.

– Roger S. Blumenthal, MD

Director, The Johns Hopkins Ciccarone Center
for the Prevention of Heart Disease

There is a lot of conversation about whether metabolic syndrome exists or not, whether it should be abolished and we should stop using the term. This study adds to the information that when looking at all of these abnormalities together, metabolic syndrome does confer a higher CV risk. Patients with metabolic syndrome had a 14.5% five-year CVD event rate compared with 11.3% for those who did not have metabolic syndrome. Metabolic syndrome increased the risk by about 28%, which is quite substantial. Despite this increased risk, patients with metabolic syndrome saw similar reductions in CV risk with fenofibrate (11%) as individuals without metabolic syndrome (12%). Surprisingly, neither reduction was statistically significant. These findings further reflect the confusion surrounding metabolic syndrome. Clinically, these findings are meaningful because I have considered metabolic syndrome as a marker of increased CV risk and this study confirms that. It does not tell us that fenofibrate is a way to reduce that risk, but at least it is confirmed that the constellation of abnormalities known as metabolic syndrome confer a higher CV risk.

– Anuj Bhargava, MD, MBA, CDE

President, Iowa Diabetes
and Endocrinology Research Center