Impacts of ezetimibe on risks of various types of cancers: a meta-analysis and systematic review

BACKGROUND: Ezetimibe is a widely used medication to reduce the plasma cholesterol level, particularly low-density lipoprotein level. However, its impact on cancer remains controversial. Here, its impacts on risks of various types of cancers were meta-analyzed. METHODS: PubMed and Cochrane Library electronic databases were searched and randomized controlled trials with followed up for at least 24 weeks were selected and included. The experimental group was defined as those patients treated with ezetimibe alone or with other medications, and the control group was defined as those who received a placebo or the matched medication. The number of new cancer cases or cancer-related deaths was extracted. Statistical analysis was performed using Review Manager (version 5.3). RESULTS: Nine trials enrolling 35 222 patients were included in the analyses. Compared with the control group, ezetimibe increased the number of new intestine cancer patients relative risk (RR), 1.30; 95% confidence interval (CI), 1.02-1.67; P = 0.03 and had a trend to increase the number of new breast cancer patients (RR, 1.39; 95% CI, 0.98-1.98; P = 0.07). There was no significant difference in new hepatobiliary cancer, prostate cancer, skin cancer or cancer of other sites. Ezetimibe did not significantly increase the risk of new cancer in total (RR, 1.03; 95% CI, 0.96-1.11; P = 0.38), cancer-related death (RR, 1.11; 95% CI, 0.98-1.26; P = 0.10) or cancer events (RR, 1.04; 95% CI, 0.97-1.12; P = 0.30). In terms of lipid-lowering effect, ezetimibe significantly reduced total cholesterol and low-density lipoprotein cholesterol, increased high-density lipoprotein cholesterol. CONCLUSION: Ezetimibe may increase the risk of intestine cancer and has a trend of increasing the risk of breast cancer. There is no evidence to support that it increases or decreases the risk of other types.