Combination therapy of statins and fibrates in the management of cardiovascular risk

Despite the fact that statin treatment substantially reduces cardiovascular morbidity and mortality, many treated patients still experience a high residual risk. Statins lower LDL cholesterol (LDL-C), with limited effects on other lipid parameters. Fibrates improve atherogenic dyslipidemia characterized by high triglyceride and/or low HDL cholesterol levels and elevated concentrations of small dense LDL particles, with or without high LDL-C levels. Fibrates decrease cardiovascular morbidity, especially in patients with the metabolic syndrome. The purpose of this review is to provide a rationale for the combined use of statins and fibrates in the management of patients with high residual cardiovascular risk related to atherogenic dyslipidemia and persisting after single therapy.

A meta-analysis from 14 randomized trials conducted in high-risk patients reported that statin therapy is effective in reducing the proportional risk for major vascular events by 21% for each mmol/l lowering of LDL-C. However, on an average, 14% of patients still experienced an event despite being allocated to statin. Beyond LDL-C, other factors, including triglycerides, non-HDL cholesterol, HDL cholesterol, and apolipoprotein B, have been identified as factors determining residual risk, and normalization of these parameters may further decrease cardiovascular disease in patients treated with statins. Data from fibrate trials indicate that these drugs are particularly effective in reducing cardiovascular morbidity in patients with atherogenic dyslipidemia.

Reducing the residual cardiovascular risk in patients treated with statins requires addressing multiple lipid goals. In this context, future therapeutic interventions based on combination therapy, such as statins and fibrates, appear particularly promising.