Currently the world faces epidemic of several closely related conditions:
obesity,
metabolic syndrome and
type 2 diabetes (T2DM). The
lipid profile of these patients and those with
metabolic syndrome is characterized by the concurrent presence of qualitative as well as quantitative
lipoprotein abnormalities: low levels of HDL, increased
triglycerides, and prevalence of
LDL particles that are smaller and denser than normal. This
lipid phenotype has been defined as atherogenic
dyslipidemia. Overwhelming evidences demonstrate that all components of the atherogenic
dyslipidemia are important risk-factors for
cardiovascular diseases. Optimal reduction of cardiovascular risk through comprehensive management of atherogenic
dyslipidemias basically depends of the presence of efficacious
lipid-modulating agents (beyond
statin-based reduction of
LDL-C). The most important class of medications which can be effectively used nowadays to combat atherogenic
dyslipidemias is the
fibrates. From a clinical point of view, in all available 5 randomized control trials beneficial effects of major
fibrates (
gemfibrozil,
fenofibrate,
bezafibrate) were clearly demonstrated and were highly significant in patients with atherogenic
dyslipidemia. In these circumstances, the main determinant of the overall results of the trial is mainly dependent of the number of the included appropriate patients with atherogenic
dyslipidemia. In a meta-analysis of dyslipidemic subgroups totaling 4726 patients a significant 35% relative risk reduction in cardiovascular events was observed compared with a non significant 6% reduction in those without
dyslipidemia. However, different
fibrates may have a somewhat different spectrum of effects. Currently only
fenofibrate was investigated and proved to be effective in reducing microvascular complications of diabetes.
Bezafibrate reduced the severity of
intermittent claudication. Cardinal differences between
bezafibrate and other
fibrates are related to the effects on
glucose metabolism and
insulin resistance.
Bezafibrate is the only clinically available pan - (alpha, beta, gamma)
PPAR balanced activator.
Bezafibrate decreases
blood glucose level, HbA1C,
insulin resistance and reduces the incidence of T2DM compared to placebo or other
fibrates. Among major
fibrates,
bezafibrate appears to have the strongest and
fenofibrate the weakest effect on HDL-C. Current
therapeutic use of
statins as monotherapy is still leaving many patients with atherogenic
dyslipidemia at high risk for coronary events because even intensive
statin therapy does not eliminate the residual cardiovascular risk associated with low HDL and/or high
triglycerides. As compared with
statin monotherapy (effective mainly on
LDL-C levels and plaque stabilization), the association of a
statin with a
fibrate will also have a major impact on
triglycerides, HDL and
LDL particle size. Moreover, in the specific case of
bezafibrate one could expect neutralizing of the adverse pro-diabetic effect of
statins. Though
muscle pain and
myositis is an issue in
statin/
fibrate treatment, adverse interaction appears to occur to a significantly greater extent when
gemfibrozil is administered. However,
bezafibrate and
fenofibrate seems to be safer and better tolerated. Combined
fibrate/
statin therapy is more effective in achieving a comprehensive
lipid control and may lead to additional cardiovascular risk reduction, as could be suggested for
fenofibrate following ACCORD
Lipid study subgroup analysis and for
bezafibrate on the basis of one small randomized study and multiple observational data. Therefore, in appropriate patients with atherogenic
dyslipidemia fibrates- either as monotherapy or combined with
statins - are consistently associated with reduced risk of cardiovascular events.
Fibrates currently constitute an indispensable part of the modern anti-dyslipidemic arsenal for patients with atherogenic
dyslipidemia.