title: Ezetimibe-Statin Combination Therapy.
abstract: BACKGROUND
  To date, most clinical comparisons of ezetimibe-statin combination therapy versus statin monotherapy have relied entirely on surrogate variables. In this systematic review, we study the efficacy and safety of ezetimibe-statin combination therapy in comparison to statin monotherapy in terms of the prevention of cardiovascular events in hyperlipidemic patients with atherosclerosis and/or diabetes mellitus.
  
  
  METHODS
  This review is based on a systematic literature search (1995 to July 2015) in PubMed, the Excerpta Medica Database (EMBASE), the Cochrane Library, and the ClinicalTrials.gov registry.
  
  
  RESULTS
  Nine randomized, controlled trials with data from a total of 19 461 patients were included. Ezetimibe-statin combination therapy was associated with a lower risk of cardiovascular events than statin monotherapy: 33% of the patients treated with ezetimibe and a statin, and 35% of those treated with a statin alone, had a cardiovascular event within seven years (number needed to treat [NNT]: 50 over 7 years). Combination therapy was also significantly more effective in preventing a composite endpoint consisting of death due to cardiovascular disease, nonfatal myocardial infarction, unstable angina pectoris, coronary revascularization, and nonfatal stroke (hazard ratio [HR] 0.94, 95% confidence interval [0,89; 0,99]; p = 0.016). Diabetic patients benefited from combination therapy rather than monotherapy with respect to cardiovascular morbidity (HR 0.87 [0.78; 0.94]). On the other hand, the addition of ezetimibe to statin therapy did not lessen either cardiovascular or overall mortality. Serious undesired events occurred in 38% of the patients taking ezetimibe and a statin nd in 39% of the patients taking a statin alone (relative risk 1.09 [0.77; 1.55]).
  
  
  CONCLUSIONS
  In high-risk patients with an acute coronary syndrome, combination therapy with ezetimibe and a statin lowered the risk of cardiovascular events in comparison to statin monotherapy. The risk of dying or suffering an adverse drug effect was similar in the two treatment groups.
authors.affiliation: Danube University Krems, Department for Evidence-based Medicine and Clinical Epidemiology, Krems an der Donau, Austria, Research Triangle Institute International, New York, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Nußbaumer
authors.forename: Anna
authors.initials: A
authors.lastname: Glechner
authors.forename: Angela
authors.initials: A
authors.lastname: Kaminski-Hartenthaler
authors.forename: Peter
authors.initials: P
authors.lastname: Mahlknecht
authors.forename: Gerald
authors.initials: G
authors.lastname: Gartlehner
mesh_terms: D054058:Acute Coronary Syndrome / Q000401:mortality* / Q000517:prevention & control*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000008:administration & dosage; D015984:Causality; D015897:Comorbidity; D016757:Death, Sudden, Cardiac / Q000453:epidemiology; D003920:Diabetes Mellitus / Q000401:mortality / Q000517:prevention & control; D004338:Drug Combinations; D064420:Drug-Related Side Effects and Adverse Reactions / Q000401:mortality*; D019317:Evidence-Based Medicine; D000069438:Ezetimibe / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D004338:Drug Combinations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069438:Ezetimibe