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.