Clinical Question: In patients with type 2 diabetes, does fenofibrate (Tricor) prevent coronary events?
Setting: Outpatient (any)
Study Design: Randomized controlled trial (double-blinded)
Synopsis: In this study, nearly 10,000 patients between 50 and 75 years of age with type 2 diabetes were randomly assigned to receive 200 mg micronized fenofibrate every day or a matching placebo. The patients all had a total cholesterol level between 115 mg per dL (3.0 mmol per L) and 250 mg per dL (6.5 mmol per L), plus a total cholesterol per high-density lipoprotein cholesterol ratio of 4.0 or higher, or a triglyceride level between 88 and 440 mg per dL (1 and 5 mmol per L), with no clear indication for, or treatment with, lipid-modifying therapy at the start of the study. After randomization, the patients were seen every four to six months for up to five years. Subsequent decisions about adding other medications were left to the discretion of the treating physician. The study was designed to have enough power to detect modest differences in the rate of events.
The outcomes for this study were analyzed by intention to treat and were assessed by evaluators unaware of the treatment group. The median follow-up was five years, and the researchers were able to account for more than 99 percent of the patients. The patients treated with placebo were more likely to receive subsequent nonstudy lipid-lowering medications (17 versus 8 percent). There was no significant difference in coronary events (6 versus 5 percent) between groups, although patients treated with placebo had more non-fatal myocardial infarctions (8.4 versus 6.4 percent; number needed to treat [NNT] = 100; 95% confidence interval [CI], 58 to 406). Patients taking fenofibrate also were less likely to have a cardiovascular event (NNT = 69; 95% CI, 36 to 1,060) or revascularization (NNT = 67; 95% CI, 40 to 194).
A systematic review (Studer M, et al. Effect of different antilipidemic agents and diets on mortality: a systematic review. Arch Intern Med April 11, 2005;165:725–30) of fibrates has shown a significant increase in all-cause mortality (number needed to harm = 132 for 4.4 years). In this study, there also was a non-significant increase in all-cause mortality (14.2 versus 12.9 per 1,000 patients; P = .18).
Bottom Line: Patients with type 2 diabetes treated with fenofibrate have no significant reduction in coronary events compared with patients treated with placebo, according to this study. There was a small reduction in nonfatal myocardial infarctions, total cardiovascular disease, and revascularization. (Level of Evidence: 1b)