Combination therapy with an HMG-CoA reductase inhibitor and a fibric acid derivative: a critical review of potential benefits and drawbacks.

It has been clearly shown that lowering low density lipoprotein-cholesterol (LDL-C) [most often with an HMG-CoA reductase inhibitor] decreases the risk of a cardiovascular event. However, this risk reduction was, at most, 35% in clinical trials, meaning that many events could not be prevented. Moreover, reaching target lipid values as recommended by the current guidelines is often difficult, mainly in high-risk situations such as secondary prevention or type 2 diabetes mellitus. As the two main classes of lipid-lowering drugs (HMG-CoA reductase inhibitors and fibric acid derivatives) have complementary effects on lipid parameters, it seems logical to combine both treatments particularly in patients with combined hyperlipidemia. In fact, combination therapy with an HMG-CoA reductase inhibitor and a fibric acid derivative induces a further decrease in LDL-C levels compared with monotherapy and improves other lipid values such as high density lipoprotein-cholesterol (HDL-C) and triglyceride (TG) levels. Unfortunately, there are currently no available randomized, prospective clinical data on the reduction of the incidence of cardiovascular events with such a combination. This is mainly because the use of HMG-CoA reductase inhibitor and fibric acid derivative combinations was initially described as dangerous. It is true that such a combination increases the risk of muscle toxicity that already exists with monotherapy. Muscle toxicity can eventually lead to life-threatening rhabdomyolysis and some precautions of use are required; however, the risk seems actually lower than what has been initially reported. The use of combined therapy with an HMG-CoA reductase inhibitor and a fibric acid derivative requires the respect of some rules such as avoiding the prescription in patients with concomitant conditions like renal failure and avoiding the use of gemfibrozil as a fibric acid derivative in such a combination. It is now imperative to design clinical trials to determine the clinical efficacy and precise safety of this combined treatment especially in patients with abnormalities in every parameter of the lipid triad (LDL, HDL and TG) and a high vascular risk such as patients with type 2 diabetes mellitus.