When a balanced diet, associated with a regular program of physical activity, is not enough to restore the values of cholesterol and triglycerides in the blood, it is necessary to intervene with specific drugs.
These include statins, ezetimibe and, indeed, fibrates (clofibrate, bezafibrate, gemfibrozil, fenofibrate).
Action mechanism
Fibrates carry out their lipid-lowering activity by acting at different levels. The main mechanism of action concerns the stimulation on the catabolism of VLDL (lipoprotein particles used to transport triglycerides, and to a lesser extent cholesterol, in the blood). This activity is mediated by the activation of lipoprotein lipase or LPL (a plasma enzyme that hydrolyzes circulating triglycerides).
In addition to increasing the rate at which they are removed from the circulation, fibrates reduce the synthesis of VLDL in the liver.
Regarding cholesterol, this class of drugs facilitates the elimination of bile and blocks the activity of HMG-CoA reductase (a liver enzyme responsible for cholesterol production). The stimulation of fibrates on the synthesis of Apo A1 lipoprotein allows to slightly raise also the levels of good cholesterol.
Effectiveness
Fibrates lower cholesterol levels to a lesser extent than statins, but have shown greater efficacy in decreasing plasma triglyceride levels. Taken in the form of tablets or capsules, they increase the good HDL cholesterol by 10-15%, while the reduction of triglycerides settles on average around 40-45%. Fibrates can also contribute to the reduction of LDL cholesterol levels, from 5 up to a maximum of 18 percentage points.
Some fibrates (bezafibrate and fenofibrate) reduce the plasma concentration of fibrinogen, a protein involved in the blood coagulation process. By reducing fibrinogenemia and platelet aggregation, these fibrates decrease the density of the blood, making it even less prone to the formation of thrombi (clots that form in the vessels and are very dangerous to health).
Intake doses
From 200 to 900 mg / day, depending on the molecule.
Side effects
In general, if taken alone, fibrates are well tolerated, although they can cause small gastrointestinal disorders. Their efficacy and safety has been extensively studied and consolidated over time, since they have entered therapy for several years (clofibrate was introduced to the clinic in 1962).
Since fibrates are almost completely eliminated via the kidneys, they must be administered at reduced dosages in patients suffering from renal insufficiency. Particular caution also in the presence of liver pathologies and in the simultaneous intake of toxic substances for the liver (including alcohol!). For this reason, even healthy patients treated with fibrates should check their liver's health every six months, undergoing simple blood tests (transaminase + hemochromocytometric assay).
More rare side effects are rash and impotence; some fibrates, due to an increase in the saturation of cholesterol contained therein, make bile more prone to forming stones.
Only for people with particularly severe hyperlipidemia is the simultaneous intake of statins and fibrates, and in any case for limited periods. In fact, this combination significantly raises the adverse effects of the two drugs, which recognize two common side effects in liver toxicity and in the appearance of pain and muscle tension.
Fibrates should not be taken during pregnancy and lactation.
