Impact of early initiation of ezetimibe in patients with acute coronary syndrome: A systematic review and meta-analysis.

OBJECTIVE: Scant data is available on the efficacy and safety of adding ezetimibe to high-intensity statin therapy for early and rapid reduction of low-density lipoprotein cholesterol (LDL-C) within 4-12 weeks of an acute-event in acute coronary syndrome (ACS). We undertook this meta-analysis to address this knowledge-gap.

METHODS: Electronic databases were searched for RCTs involving patients with ACS receiving ezetimibe in intervention arm, and placebo/active comparator in control arm. Primary outcome was to evaluate changes in LDL-C levels post-ACS. Secondary outcomes were to evaluate alterations in other lipid parameters and adverse events.

RESULTS: From initially screened 4561 articles, data from 11 studies (20,291 patients) were analyzed. Compared to controls, patients receiving ezetimibe had significantly lower LDL-C at 7-days [MD -19.55 mg/dl(95 %CI:-36.46 to -2.63);P = 0.02;I2 = 91 %], 1-month [MD-24.67 mg/dl (95 %CI:-34.59 to -14.76);P < 0.001;I2 = 81 %], 3-months [MD -18.01 mg/dl(95 %CI:-24.11 to -11.90);P < 0.001;I2 = 92 %] and 10-12 months [MD -16.90 mg/dl (95 % CI: -17.67 to -16.12); P < 0.001; I2 = 0 %] of treatment. Compared to controls, patients receiving ezetimibe had significantly lower total cholesterol at 7-days [MD-21.05 mg/dl(95 %CI:-26.73 to -15.37);P < 0.001;I2 = 0 %], 1-month [MD-25.56 mg/dl(95 %CI:-38.29 to -12.83);P < 0.001;I2 = 85 %], 3-months [MD-22.54 mg/dl(95 %CI:-36.90 to -8.19);P = 0.002;I2 = 22 %] and 12-months [MD-19.68 mg/dl(95 %CI:-20.78 to -18.59);P < 0.001;I2 = 0 %] of treatment. Death from any cause, ACS and non-fatal stroke [OR0.89(95 %CI:0.83-0.96);P = 0.002;I2 = 0 %], non-fatal myocardial infarction [OR0.86(95 %CI:0.79-0.94);P = 0.001;I2 = 0 %] and ischemic stroke [OR0.80(95 %CI:0.68-0.94);P = 0.009;I2 = 0 %] was significantly reduced in patients receiving ezetimibe.

CONCLUSION: Addition of ezetimibe to high-intensity statin therapy at the time of ACS event is associated with significantly better cholesterol reduction at day-7,1-month, 3- months and 1-year of follow-up, which translates into a significantly lower recurrent cardiovascular events post an index event of ACS.

CONCISE SUMMARY OF FINDINGS: Addition of ezetimibe to high-intensity statin therapy at the time of acute coronary syndrome (ACS) index event is associated with significantly better low density lipoprotein cholesterol and total cholesterol reduction at day-7, 1-month, 3-months and 1-year of follow-up, which translates into a significantly lower recurrent cardiovascular events (death from any cause, major ACS, non-fatal stroke, non-fatal myocardial infarction, and ischemic stroke) post an index event of ACS.