simvastatin/fenofibrate combination in the treatment of dyslipidemia: current evidence

Jose G Jimenez-Montero,1 Gregory Haft2 1Post Graduate Studies, University of Medical Sciences, San José, Costa Rica; 2Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA Background: It has been demonstrated that statins can reduce major cardiovascular complications throughout a broad range of patients with dyslipidemia and multiple cardiovascular risk. Despite the impact of statin therapy on cardiovascular morbidity and mortality, a residual cardiovascular risk remains following lowering of low-density lipoprotein cholesterol. In many patients, optimization of the lipid profile cannot be achieved with statin therapy. Therefore, pharmacologic interventions with non-statin therapy can be used. Aims: The objective of this review was to analyze current clinical evidence of the effects of simvastatin/fenofibrate combination therapy. Methods: We searched and analyzed the evidence up to June 2014, regarding the effects of statin/fibrate combination therapy for reducing cardiovascular complications. Results: Forty-nine studies reporting the efficacy and safety of statin/fibrate combination therapy were analyzed. Of the forty-nine, 19 analyzed the simvastatin/fenofibrate combination therapy. This therapy was demonstrated to be safe and superior to the statin monotherapy in modifying atherogenic dyslipidemia, including lipoprotein subclasses. Nevertheless, in randomized clinical trials cardiovascular endpoints were not significantly different when fenofibrate was added to a standard low-density lipoprotein cholesterol reducing therapy. Of note, in the subgroup analysis, positive results were observed in patients with high triglycerides and low high-density lipoproteins. The inclusion of heterogeneous populations in these studies may explain the mixed results of cardiovascular outcomes seen in randomized clinical trials. Conclusion: Future clinical studies that rigorously address the effects of simvastatin/fenofibrate in patients with triglycerides >2.25 mmol/L and high density lipoprotein cholesterol <0.90 mmol/L, will provide a more accurate conclusion regarding the use of simvastatin/fenofibrate combination therapy. For now, emphasis must be put on non-pharmacological interventions that effectively induce weight loss and strict glycemic control in diabetics. The initiation of simvastatin/fenofibrate combination therapy among patients with residual cardiovascular risk should be employed at the physician's discretion, as this strategy lacks hard cardiovascular end points. Keywords: dyslipidemia, atherosclerotic cardiovascular disease, residual risk, simvastatin fenofibrate combination therapy