Published online Nov 26, 2014. doi: 10.13105/wjma.v2.i4.194
Revised: June 24, 2014
Accepted: September 6, 2014
Published online: November 26, 2014
AIM: To evaluate the efficacy, effect of preventing cardiovascular diseases and safety of statins-fibrates combination therapy in diabetic dyslipidemia patients.
METHODS: We searched the databases of MEDLINE, EMBASE, web of knowledge and Cochrane central register of Controlled Trials for literatures about the coadministration of statins and fibrates as the treatment of patients with dyslipidemia and type 2 diabetes mellitus. We included related randomized controlled trials, controlled clinical trials and cross-sectional studies and excluded animal trials and clinical observations. The primary endpoints outcomes were the concentration of plasma total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). The secondary outcomes were cardiovascular diseases (CVD) and adverse events.
RESULTS: Ten studies were included in this meta-analysis. For lipid modifying efficacy, the combination of statins and fibrates therapy had more significant effect on reducing TC [P = 0.004, weighted mean difference (WMD) = -8.19, 95%CI: -13.82--2.56] and TG concentration (P < 0.001, WMD = -47.29, 95%CI: -68.66--25.92) and increasing HDL-C concentration (P < 0.00001, WMD = 3.79, 95%CI: 2.25-5.33) when compared with statins monotherapy, while the effect of reducing LDL-C concentration (P = 0.50, WMD = -2.52, 95%CI: -9.76-4.72) was insignificant. To fibrates monotherapy, the combination therapy was more effective on reducing TC (P < 0.00001, WMD = -48.51, 95%CI: -57.14--39.89), TG (P < 0.00001, WMD = -26.07, 95%CI: -30.96--21.18), LDL-C concentration (P < 0.00001, WMD = -45.74, 95%CI: -53.35--38.13) and increasing HDL-C concentration (P = 0.04, WMD = 1.38, 95%CI: 0.04-2.73). For cardiovascular diseases, the coadministration therapy had no significant effect on reducing the incidence of these events when compared with monotherapy (For primary clinical endpoints, P = 0.12, OR = 0.61, 95%CI: 0.33-1.14); for secondary clinical endpoints, P = 0.13, OR = 0.66, 95%CI: 0.38-1.14). For adverse events happened during the follow-up, both the incidence of hepatic-related (alanine aminotransferase and/or aspartate aminotransferase of patients were ≥ 3 times of upper limit of normal) (P = 0.38, OR = 0.55, 95%CI: 0.15-2.06) and muscular-related (myopathy and/or creatine phosphokinase ≥ 3 times of upper limit of normal) adverse events (P = 0.10, OR = 1.62, 95%CI: 0.91-2.86) had no significant difference between these two therapies.
CONCLUSION: The results showed statins-fibrates combination therapy was more effective on lipid modification and well tolerated but there was no significant effect on preventing cardiovascular diseases.
Core tip: Both dyslipidemia and type 2 diabetes were established risk factors of cardiovascular diseases. Statins therapy was highly effective at lowering low density lipoprotein cholesterol (LDL-C). However, despite the increasing use of statins as monotherapy for LDL-C reduction, a significant residual cardiovascular risk was still presented in patients with diabetic dyslipidemia. At the same time, Fenofibrate failed to alter the primary clinical endpoints significantly. How about the efficacy of statins-fibrates combination therapy in patients with diabetic dyslipidemia? The results of this meta-analysis showed the combination therapy was more effective on lipid modification and well tolerated but there was no significant effect on preventing cardiovascular diseases.