title: Addition of Ezetimibe to statins for patients at high cardiovascular risk: Systematic review of patient-important outcomes.
abstract: Ezetimibe is widely used in combination with statins to reduce low-density lipoprotein. We sought to examine the impact of ezetimibe when added to statins on patient-important outcomes. Medline, EMBASE, CINAHL, and CENTRAL were searched through July, 2016. Randomized controlled trials (RCTs) of ezetimibe combined with statins versus statins alone that followed patients for at least 6 months and reported on at least one of all-cause mortality, cardiovascular deaths, non-fatal myocardial infarctions (MI), and non-fatal strokes were included. Pairs of reviewers extracted study data and assessed risk of bias independently and in duplicate. Quality of evidence was assessed using the GRADE approach. We conducted a narrative review with complementary subgroup and sensitivity analyses. IMPROVE-IT study enrolled 93% of all patients enrolled in the 8 included trials. Our analysis of the IMPROVE-IT study results showed that in patients at high risk of cardiovascular events, ezetimibe added to statins was associated with i) a likely reduction in non-fatal MI (17 fewer/1000 treated over 6 years, moderate certainty in evidence); ii) a possible reduction in non-fatal stroke (6 fewer/1000 treated over 6 years, low certainty); iii) no impact on myopathy (moderate certainty); iv) potentially no impact on all-cause mortality and cardiovascular death (both moderate certainty); and v) possibly no impact on cancer (low certainty). Addition of ezetimibe to moderate-dose statins is likely to result in 17 fewer MIs and possibly 6 fewer strokes/1000 treated over 6 years but is unlikely to reduce all-cause mortality or cardiovascular death. Patients who place a high value on a small absolute reduction in MI and are not adverse to use of an additional medication over a long duration may opt for ezetimibe in addition to statin therapy. Our analysis revealed no increased specific harms associated with addition of ezetimibe to statins.
authors.affiliation: Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.|Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Fei
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.|Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Gordon Henry
authors.initials: GH
authors.lastname: Guyatt
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Paul Elias
authors.initials: PE
authors.lastname: Alexander
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.|Department of Anaesthesiology, Botucatu Medical School, Unesp - Univ Estadual Paulista, São Paulo, Brazil.
authors.forename: Regina
authors.initials: R
authors.lastname: El Dib
authors.affiliation: Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Reed A C
authors.initials: RAC
authors.lastname: Siemieniuk
authors.affiliation: Department of Medicine, Innlandet Hospital Trust-Division Gjøvik, Oppland, Norway.
authors.forename: Per Olav
authors.initials: PO
authors.lastname: Vandvik
authors.affiliation: New york University School of Medicine, New York, US.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Nunnally
authors.affiliation: Department of Pharmacy, Tanta Chest Hospital, Tanta, Egypt.
authors.forename: Huda
authors.initials: H
authors.lastname: Gomaa
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Morgan
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.|School of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Arnav
authors.initials: A
authors.lastname: Agarwal
authors.affiliation: Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Health Sciences Library, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Neera
authors.initials: N
authors.lastname: Bhatnagar
authors.affiliation: Department of Internal Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Spencer
mesh_terms: D000924:Anticholesteremic Agents / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D000069438:Ezetimibe / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D063868:Patient Outcome Assessment
chemical_list: D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069438:Ezetimibe
keywords: ezetimibe; lipid; meta-analysis; statins; systematic review