No published clinical outcome trials that examined the cardiovascular benefit of ezetimibe were identified. Thirteen multicentre RCTs with surrogate end-point data were included in the review. None of the trials reported allocation concealment. Five trials did not clarify whether outcome assessors were blinded. All patients were blinded, although none of the trials assessed the success of blinding. All trials except one used ITT or modified ITT analysis. Most trials reported a power calculation. Overall trials were considered by the authors to be relatively well designed and conducted and included relatively balanced populations.
Fixed-dose combination therapy (for those inadequately controlled by statin): The combination of ezetimibe and statin was associated with a statistically significant reduction in LDL-C (-13.94%, 95% CI -14.90 to -12.98, p<0.00001, I2=5.8%) and total cholesterol (-10.36%, 95% CI -11.09 to -9.63, p<0.00001, I2=5.65%) compared with statin alone based on six trials (3,610 patients). No RCTs of ezetimibe plus statin compared to other lipid-lowering drugs were identified.
Titrated Combination therapy (for those inadequately controlled by statin): All four trials (1,800 patients) found that co-administration of ezetimibe and statin was significantly more effective in reducing LDL-C (p<0.05) compared with statin alone. One study compared ezetimibe plus statin verus other lipid-lowering drugs. This study found that low-moderate doses of atorvastatin/rosuvastatin plus niacin achieved similar LDL-C reductions compared with the highest doses of rosuvastatin monotherapy or ezetimibe/simvastatin.
Monotherapy (for those where a statin was inappropriate or not tolerated): All included studies compared monotherapy with placebo. A meta-analysis of all seven trials (2,577 patients) demonstrated that ezetimibe significantly reduced LDL-C levels compared with placebo (WMD -18.56, 95% CI -19.68 to -17.44, I2=55.4%).
There were no significant differences in LDL-C across subgroups based on various patient characteristics.
Ezetimibe therapy appeared to be well tolerated compared to statin monotherapy or to placebo. The low frequency of adverse events may have been related to the short follow-up time. Long-term adverse effects were unknown.
No studies of HRQoL data were located.