An estimated 80 million Americans have cardiovascular disease (CVD).1 CVD causes one out of every 2.8 deaths in the United States. The use of HMG CoA reductase inhibitors (statins) produces significant reductions in coronary heart disease events and mortality; therefore, statins are currently the drug of choice in high risk patients. However, it is controversial whether their reduction in LDL-cholesterol is the only mechanism of action responsible for these benefits. There are conflicting data on the relationship between triglycerides and CVD. Fibrates are frequently used to treat patients with elevated triglyceride levels. Fibrates also raise HDL-cholesterol and potentially change small, dense, more atherogenic LDL particles into larger, less atherogenic particles.
A systematic review by Abourbih and colleagues investigated the effects of fibrates on lipid profiles and cardiovascular outcomes.2 Double-blind, placebo-controlled trials randomizing ≥ 100 patients that had follow-up data for ≥ 8 weeks and were published in English before June 2007 were reviewed. 1,376 studies were identified and twenty trials (n=25,655) were included; four trials of bezafibrate (n=4984), nine trials of fenofibrate (n=12,398), and seven trials of gemfibrozil (n=8273) met the inclusion criteria. Triglycerides show the greatest improvement with the addition of bezafibrate, fenofibrate or gemfibrozil. Modest effects on LDL, HDL, and total cholesterol have been shown with fibrates when compared to placebo. However, a greater beneficial effect on HDL may be seen with bezafibrate as compared to other fibrates. Trials involving bezafibrate demonstrated up to a 17.9 mg/dL increase in HDL. Non-fatal myocardial infarction and all-cause mortality were the two cardiovascular outcomes that were consistently reported and were included in the meta-analysis.
The analysis found that fibrate therapy was associated with a decrease in nonfatal myocardial infarction compared with placebo (OR = 0.78; 95% CI, 0.69-0.89). No reduction in all-cause mortality was found (OR = 1.05; 95% CI, 0.95-1.15). In both the treatment and placebo groups, the most common adverse effect was gastrointestinal symptoms. Myalgia was a rare side effect that had a similar incident in both the treatment and placebo groups. Rhabdomyolysis only occurred in the FIELD study. Three patients taking fenofibrate and one patient taking placebo experienced rhabdomyolysis. The authors concluded that while statins remain the recommended treatment for dyslipidemia, fibrates should be considered in patients who are intolerant to statins, in patients with hypertriglyceridemia, or as an adjunct to statin therapy.
Triglycerides greater than 1000 mg/dL require treatment with fibrates to reduce the risk of pancreatitis; lifestyle modifications should be first line in those patients with mild-to-moderate elevations in triglyceride levels.3 Statin-fibrate combinations increase the risk of muscle toxicity (rhabdomyolysis or myalgia) as compared to either statins or fibrates alone. Additionally, greater cardiovascular event reduction has not been demonstrated with a statin-fibrate combination as compared to a statin alone. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study is examining the combination of fenofibrate and simvastatin versus simvastatin alone on cardiovascular outcomes. Results are expected this year. Therefore, at this time, statin-fibrate combinations should be used with caution.
1. American Heart Association Statistics ...