Efficacy And Safety Of Ezetimibe Added To Statin Versus Statin Alone:a Meta-analysis

BackgroundThe data of DYSIS-China in 2013 shows mat 70% of patients with dyslipidemia were in very high risk/high risk of cardiovascular disease; although most patients use medium or high dose of statins, only 61.5% patients’ LDL-C reach the standard, and increasing the dose of statins didn’t improve the good-control rate. According to the current situation, on the one hand we should regulate lipid according to the new guide, on the other hand combination drug therapy may be a good choice.Ezetimibe has been widely used since coming into the market in 2002. Many clinical experiments have observed the effect of the combination of Ezetimibe and statins. Most of them have showed that combination of Ezetimibe and statins have better cure effects than single using statins, but other experiments made different conclusion. More data is needed to make judgment between these two therapy methods and more clinical trials are needed to compare the therapeutic effect and the reverse effect.ObjectivesThis meta-analysis was designed to assess the therapeutic effect and reverse effect between combination of Ezetimibe and statins and single using statins, in order to provide additional evidence for clinical doctors’decision.MethodsWe search the randomized clinical trials about Ezetimibe and statins in pubmed, CNKI and Wanfang Data. The comparative changes in LDL-C and adverse effect before and after therapy were calculated. Results were expressed as standard mean difference (SMD) or odds ratio (OR) with 95% confidence intervals (CI). P<0.05 was considered statistically significant.ResultsA total of 43 randomized controlled trials (RCT) were included. Among them,14 studies were about combination of Ezetimibe and statin compared with single dose of statin; 27 studies were about combination of Ezetimibe and statin compared with double dose/potency of statin; 10 studies were about combination of Ezetimibe and statin compared with quadruple dose/potency of statin and 1 studies were about combination of Ezetimibe and statin compared with eightfold dose of statin.1. Ezetimibe combined with statin vs. single dose of statin(1) Compared with single dose of statin, Ezetimibe combined with statin decreases more LDL-C level obviously (SMD=1.01; 95%CI:[0.82,1.21], P<0.00001).Subgroup analysis:① Compared with single dose of rosuvastatin, ezetimibe combined with rosuvastatin decreases more LDL-C level obviously (SMD=1.05; 95%CI:[0.82,1.28], P<0.00001).② Compared with single dose of atorvastatin, Ezetimibe combined with atorvastatin decreases more LDL-C level obviously (SMD=0.83; 95%CI:[0.60,1.07], P<0.00001).③ Compared with single dose of simvastatin, Ezetimibe combined with simvastatin decreases more LDL-C level obviously (SMD=1.02; 95%CI:[0.59,1.46], P<0.00001).④ Compared with single dose of pravastatin, Ezetimibe combined with pravastatin decreases more LDL-C level obviously (P<0.01).(2) Compared with single dose of statin, Ezetimibe combined with statin doesn’t increase the rate of reverse effect (OR=0.87; 95%CI [0.46,1.67], P=0.69).2. Ezetimibe combined with statin vs. double dose/potency of statin(1) Compared with double dose/potency of statin, Ezetimibe combined with statin decreases more LDL-C level obviously (SMD=2.72; 95%CI:[2.07,3.38], P<0.00001).Subgroup analysis:① Compared with double dose of rosuvastatin, ezetimibe combined with rosuvastatin decreases more LDL-C level obviously (SMD=1.96; 95%CI:[0.25,3.67], P=0.02).② Compared with double dose of atorvastatin, Ezetimibe combined with atorvastatin decreases more LDL-C level obviously (SMD=2.82; 95%CI:[1.50,4.14], P<0.0001).③ Compared with double dose of simvastatin, Ezetimibe combined with simvastatin decreases more LDL-C level obviously (SMD=1.74; 95%CI:[0.58,2.90], P=0.003).④ Compared with double potency of other statin, Ezetimibe combined with simvastatin decreases more LDL-C level obviously (SMD=3.63; 95%CI:[2.43,4.83], P<0.00001).(2) Compared with double dose/potency of statin, Ezetimibe combined with statin doesn’t increase the rate of reverse effect (OR=0.95; 95%CI [0.66,1.38], P=0.80).3. Ezetimibe combined with statin vs. quadruple dose/potency of statin(1) Compared with quadruple dose/potency of statin, Ezetimibe combined with statin shows no difference in decreasing LDL-C level (SMD=-0.14; 95%CI:[-0.74, 0.45], P=0.64).Subgroup analysis:① In Daisuke Yamazaki’s study, compared with 10 mg rosuvastatin,10 mg ezetimibe combined with 2.5 mg rosuvastatin shows no difference in decreasing LDL-C level.② In Wei Liang’s study, compared with 40mg atorvastatin,10 mg Ezetimibe combined with 10 mg atorvastatin shows no difference in decreasing LDL-C level.③ Compared with quadruple dose of simvastatin, Ezetimibe combined with simvastatin shows no difference in decreasing LDL-C level (SMD=0.50; 95%CI: [-0.16,1.17], P=0.14).④ Compared with quadruple potency of rosuvastatin, Ezetimibe combined with simvastatin shows no difference in decreasing LDL-C level (SMD=-0.94; 95%CI: [-1.88,0.00], P=0.05).⑤ In Kozo Okada’s study, compared with atorvastatin 20mg, ezetimibe 10mg combined with rosuvastatin 2.5mg decrease more LDL-C level obviously (P=0.004).(2) Compared with quadruple dose/potency of statin, Ezetimibe combined with statin doesn’t increase the rate of reverse effect.4. Ezetimibe combined with statin vs. eightfold dose of statinIn Mir Abolfazl Ostad’s study, compared with 80mg atorvastatin, 10mg ezetimibe combined with 10mg atorvastatin shows no difference in decreasing LDL-C level; the article doesn’t show the rate of reverse effect.Conclusions1. Combination of Ezetimibe and Rosuvastatin have more effect in decreasing LDL-C level compared with single use of double dose of Rosuvastatin, but shows no difference compared with quadruple dose of Rosuvastatin.2. Combination of Ezetimibe and Atorvastatin have more effect in decreasing LDL-C level compared with single use of double dose of Atorvastatin, but shows no difference compared with quadruple and eightfold dose of Rosuvastatin.3. Combination of Ezetimibe and Simvastatin have more effect in decreasing LDL-C level compared with single use of double dose of Atorvastatin, but shows no difference compared with quadruple dose of Simvastatin.4. Combination of Ezetimibe and Simvastatin have more effect in decreasing LDL-C level compared with single dose of Atorvastatin or half dose of Rosuvastatin, but shows no difference compared with single dose of Rosuvastatin.5. Ezetimibe combined with statins doesn’t improve the rate of reverse effect apparently.