Safety of coadministration of ezetimibe and statins in patients with hypercholesterolaemia: a meta-analysis

Hypercholesterolaemia is a pivotal risk factor for cardiovascular and cerebrovascular disease and is treated with many effective lipid-lowering agents. Statins are often used alone or in combination with ezetimibe. Combination therapy is more effective because of its complementary approach, which has major benefits for patients with unmanageable lipid levels. Extensive application of combination therapy has resulted in an increased incidence of side-effects, which has raised our concern.

To evaluate the evidence associated with the safety of coadministration of ezetimibe with statins.

Three electronic databases were searched (PubMed, EMBASE and Cochrane Library) from January 2002 to October 2014. Two independent reviewers critically identify randomised controlled trials (RCT), extracted the data and assessed trial quality. A total ot 20 RCT met inclusion criteria, including 14,856 patients. A fixed-effects model was used for meta-analysis to assess the safety of combination therapy.

Coadministration of ezetimibe and statins did not result in significant increases in total adverse events (30% vs 29%, P = 0.34), serious adverse events (2% vs 1.6%, P = 0.81), treatment discontinuations (3.5% vs 2.9%, P = 0.22), gastrointestinal adverse events (5% vs 4%, P = 0.08), allergic reactions or rashes (0.9% vs 1.3%, P = 0.33), creatine kinase > 10 × upper limit of normal (ULN) (0.2% vs 0.2%, P = 0.86), alanine aminotransferase > 3 × ULN (0.5% vs 0.4%, P = 0.96) and aspartate aminotransferase > 3 × ULN (0.4% vs 0.4%, P = 0.58).

The incidence of adverse events was similar between ezetimibe-statin combination therapy and statin monotherapy; thus, we recommend combination therapy for patients with hypercholesterolaemia at high risk for cardiovascular and cerebrovascular disease.