Authors
ACCORD study group
Title
Effects of combination lipid therapy in type 2 diabetes mellitus
References
N Engl J Med. 2010 Apr 29;362(17):1563-74.
Background
Patients with type 2 diabetes mellitus have an increased incidence of atherosclerotic cardiovascular disease. This increase is attributable, in part, to associated risk factors, including hypertension and dyslipidemia. Although statins are efficacious in patients with type 2 diabetes, rates of cardiovascular events remain elevated in such patients even after statin treatment. Fibrate therapy in patients with type 2 diabetes reduced the rate of coronary heart disease events in the VA-HIT trial but not in the FIELD trial.
Purpose
To test the hypothesis that in high-risk patients with type 2 diabetes, combination treatment with a fibrate (both to raise HDL cholesterol levels and to lower triglyceride levels) and a statin (to reduce LDL cholesterol levels) would reduce the rate of cardiovascular events, as compared with treatment with a statin alone.
Design
  • Multicenter, randomized, double-blind trial
  • 5518 patients age 40-79 years with DMII and HbA1c >7.5%; plus 2 CV risk factors
  • LDL between 1.55-4.65mmol/L
  • HDL <1.42mmol/L
  • Triglyceride <8.5mmol/L
Exclusion Criteria
  • Frequent or serious hypoglycemic events
  • BMI>45
  • Creatinine >133umol/L
  • Concomitant treatment with another medication known to interact with statin/fibrate
  • History of pancreatitis, myositis
Follow-Up
Mean 4.2 years
Treatment Regimen
  • Open label simvastatin began at randomization visit at a dose based on lipid guidelines
  • Fenofibrate 160mg/day or placebo starting 1 month later
  • Follow-up visits at 4, 8, and 12 months after randomization and then annually
Results

Primary Endpoints

Fenofibrate
n=2765
Event rate/yr		Placebo
n=2753
Event rate/yr		Hazard Ratiop
Major CV event (cardiac death, non-fatal MI, or non-fatal stroke)
2.2%2.4%0.92 (0.79–1.08)0.32

Secondary Outcomes

(see study for additional endpoints)

Fenofibrate
n=2765
Event rate/yr		Placebo
n=2753
Event rate/yr		Hazard Ratiop
Cardiac death
1.5%1.6%0.91 (0.75–1.10)0.33
Non-fatal MI
1.3%1.4%0.91 (0.74–1.12)0.39
Non-fatal stroke
0.4%0.3%1.17 (0.76–1.78)0.48
Summary
The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke, as compared with simvastatin alone. These results do not support the routine use of combination therapy with fenofibrate and simvastatin to reduce cardiovascular risk in the majority of high-risk patients with type 2 diabetes.