Combination Therapy

Although statin therapy has become the first-choice approach in the management of atherosclerosis, combined therapies may be advantageous as they may have synergistic effects. In the past, combination therapy has been reserved for a small minority of patients with severe dyslipidemia, due to perceived risk.

The addition of an omega-3 fatty-acid supplement to statin therapy in patients with persistent hypertriglyceridemia significantly reduced triglyceride levels and non-HDL-cholesterol levels, all without a significant increase in LDL levels⁴⁹.

The combination of a bile sequestrant with either statins, ezetimibe and fenofibrate, has an overall favourable effect on lipid profile^{50, 51}.

In cases of combined hyperlipidemia, combined therapy with statins and fibrates has been found to be more effective in controlling atherogenic dyslipidemia than either drug alone⁵². Endothelial dysfunction associated with cardiovascular diseases may contribute to insulin resistance so that there may also be additional beneficial metabolic effects of combined statin/fibrates therapy. When statins are combined with gemfibrozil therapy, this is more likely to be accompanied by myopathy. However, this limitation is not observed when fenofibrate, bezafibrate, or ciprofibrate are used in combination therapy. Rarely, patients have experienced a decrease in HDL during fibrate and statin combination treatment. The mechanism underlying this is unclear. In each case HDL was restored by withdrawal of fenofibrate⁵³.

It is evident that combination therapies carry increased risk, and therefore it is important to individually monitor and evaluate the risk-benefit ratio for each patient. Moreover, combination therapy may be associated with increased drug costs and decreased patient compliance. In general, however, it is accepted that the potential complications of this combination are far outweighed by the clinical benefits.⁵⁴