The effect of fibrates and other lipid-lowering drugs on plasma homocysteine levels.

Hyperlipidaemia is a major risk factor for cardiovascular disease. The drugs of choice for the treatment of hyperlipidaemia are either fibrates, in the case of hypertriglyceridaemia, or statins, in the case of hypercholesterolaemia. Recently, it has been shown that some of the most prescribed fibrates cause hyperhomocysteinemia, which itself has been recognised as a cardiovascular risk factor. In particular, fenofibrate and bezafibrate lead to a 20 - 40% elevation of plasma levels of the atherogenic amino acid homocysteine, thereby possibly counteracting the desired cardiovascular protection. The most likely mechanism for this increase is an alteration of creatine-creatinine metabolism and changes in methyl transfer. Gemfibrozil does not increase homocysteine. Statins have no effect on the plasma homocysteine concentration. The increase of plasma homocysteine after fenofibrate can be lowered by the concurrent administration of folic acid and vitamins B(12) and B(6). Thus, patients with hypertriglyceridaemia can either be concurrently treated with fenofibrate and vitamins or with gemfibrozil.