Fibrates
- Epidemiologic studies provide evidence of an association between triglycerides and the development of primary CVD (cardiovascular disease) events independently of HDL-C. Evidence of an inverse relationship between triglycerides and HDL-C suggests that both should be considered in CVD risk estimation and as targets for intervention.1, 2
- Fibrates are very effective in lowering the triglycerides and are used worldwide for this purpose. Although fibrates increases HDL by about 10%, the overall effect is deleterious on the its subfractions with a slight decrease in the concentration of large α-1 and slight increase in the concentration of small α-3 HDL.3
- Concentrations of the large HDL particles are inversely associated while those of the small HDL particles which are positively associated with CVD. Therefore, the effects of fibrates on HDL subclasses may be unfavorable.3 There is the possibility that fibrates protect from CVD not through increasing HDL levels but rather through other mechanisms.
- More recently, the results of the ACCORD trial have failed to convey a mandate for the use of fenofibrate by showing no benefits on CVD outcomes when adding fenofibrate to simvastatin therapy in more than 5000 diabetic subjects over 5 years. In this study, fenofibrate increased HDL-C levels by 8.4%. 4
- However, it is important to note that subjects with both low HDL (average 32 mg/dl) and high TG (average 204 mg/dl) experienced a 29% risk reduction in CVD events 4 and that, overall, fenofibrate reduced the risk of retinopathy by 40%.5
- A systematic review and meta-analysis of all trials published between 1950 and 2010 evaluated the effects of fibrates on major clinical outcomes. These outcomes were cardiovascular events, coronary events, stroke, heart failure, coronary revascularization, all-cause mortality, cardiovascular death, non-vascular death, sudden death, new onset albuminuria, and drug-related adverse events. The analysis included 18 trials providing data for 45,058 participants, including 2870 major cardiovascular events, 4552 coronary events, and 3880 deaths. 2
- Fibrate therapy produced a 10% reduction in major cardiovascular events and a 13% reduction in coronary events but had no benefit on stroke, all-cause mortality, cardiovascular mortality, sudden death, or non-vascular mortality. Fibrates reduced the risk of albuminuria progression by 14%. Serious drug-related adverse events were not significantly increased by fibrates although increases in serum creatinine concentrations were common.2
- Fibrate sales exceed $1 billion in the US. During the past decade, prescriptions for fibrates (particularly fenofibrate) increased in the United States, while prescriptions for fibrates in Canada remained stable.6
Sources
1. Morrison A, Hokanson JE. The independent relationship between triglycerides and coronary heart disease. Vasc Health Risk Manag. 2009;5(1):89-95.
2. Jun M, Foote C, Lv J, et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet. May 29 2010;375(9729):1875-1884.
3. Asztalos BF. HDL particles, coronary artery disease and niacin. J Clin. lipidology. 2010;4:405-410.
4. Ginsberg HN, Elam MB, Lovato LC, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. Apr 29 2010;362(17):1563-1574.
5. Klein B E. Reduction in risk of progression of diabetic retinopathy. N Engl J Med. Jul 15 2010;363(3):287-288.
6. Jackevicius CA, Tu JV, Ross JS, Ko DT, Carreon D, Krumholz HM. Use of fibrates in the United States and Canada. JAMA. Mar 23 2011;305(12):1217-1224.