Results from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial showed that a combination of fenofibrate and simvastatin failed to reduce risk of fatal cardiovascular events compared to simvastatin alone.
The results were presented at the American College of Cardiology (ACC) 2010 scientific sessions in Atlanta, USA, on 14 March by Henry Ginsberg (Columbia University, New York, USA).
Ginsberg concluded that the “findings do not support the use of combination fibrate-statin therapy, rather than statin therapy alone, to reduce cardiovascular risk in the majority of patients with type 2 diabetes who are at high risk for cardiovascular disease.”
Ginsberg told delegates that ACCORD, a randomised, placebo-controlled, double-blind clinical trial conducted in 77 clinical sites in the USA and Canada, was designed to independently test three medical strategies to reduce cardiovascular disease in diabetic patients and aimed to address the question of whether combination therapy with a statin plus a fibrate would reduce cardiovascular disease compared to statin monotherapy in people with type 2 diabetes mellitus at high risk for cardiovascular disease.
In the trial, a total of 10,251 high-risk type 2 diabetes patients were randomly assigned to either intensive or standard glycaemic control. Also, 4,733 of the participants were also randomised to either intensive or standard blood-pressure control, and 5,518 patients were randomly assigned to simvastatin plus fenofibrate or simvastatin plus placebo.
Due to higher mortality in the group assigned to intensive glycaemic control group, the glycaemic-control ACCORD study was stopped early. In the ACCORD lipid trial, patients were followed for a mean of 4.7 years. After this time there were 291 major fatal or nonfatal cardiovascular events in the fenofibrate-statin-therapy study arm (2.24%/year) and 310 events in the statin-therapy-alone arm (2.41%/year). The difference was not statistically significant (p=0.32).
Ginsberg concluded from the results that ACCORD does not support the use of the combination of fenofibrate and simvastatin compared to simvastatin alone to reduce cardiovascular events in the majority of patients with type 2 diabetes who have HDL-C and TG levels that are close to the normal range.
Subgroup analyses, however, did suggest that patients with the combination of baseline triglycerides in the upper third and HDL-cholesterol levels in the lower third of the population (TG >200 and HDL <35mg/dl) may have benefitted from fenofibrate therapy in addition to simvastatin. Further investigation is necessary to confirm this observation, but treatment of such patients is presently suggested by the Adult Treatment Guidelines. However, some experts have suggested that ACCORD adds weight to the need for those at high risk of type 2 diabetes to address lifestyle issues such as obesity and diet, rather than relying on medication.
“We do not consider the trial negative,” Ginsberg added. “We did not show benefit above standard care, but those are important positive findings. The majority of people with diabetes will not, based on our study, benefit from the addition of a fibrate to alter their triglycerides and HDL cholesterol levels. However, our subgroup analysis did suggest that about 15% of the diabetic population with very high triglycerides and very low HDL cholesterol levels may benefit. I suggest, therefore, that after statin treatment has controlled their LDL cholesterol, patients ask their doctors to look at their triglyceride and HDL levels and if there are greater than 200mg/dl and less than 35mg/dl, respectively, the doctor may consider combination therapy rather than statin treatment alone. Weight loss and exercise would be the preferred approach, but the statin-fibrate combination is safe and most likely beneficial for these individuals.”