title: Systematic review: comparative effectiveness and harms of combination therapy and monotherapy for dyslipidemia.
abstract: BACKGROUND
  Statin therapy effectively prevents vascular disease, but treatment targets are often not achieved.
  
  
  OBJECTIVE
  To compare the benefits and harms of high-dose statin monotherapy with those of combination therapy in adults at high risk for coronary disease.
  
  
  METHODS
  English-language records from MEDLINE (1966 to 2009), EMBASE (1980 to 2009), and the Cochrane Library (third quarter of 2008).
  
  
  METHODS
  A reviewer screened records, and a second reviewer verified selection of randomized, controlled trials in adult patients that compared combinations of statins and bile-acid sequestrants, fibrates, ezetimibe, niacin, or omega-3 fatty acids with statin monotherapy, as well as nonrandomized comparative studies that were longer than 24 weeks and reported clinical and harms outcomes.
  
  
  METHODS
  Data were abstracted for studies by using standardized forms, and study quality was rated with a standardized scale and strength of evidence by using the Grading of Recommendations Assessment, Development, and Evaluation approach.
  
  
  RESULTS
  102 studies met eligibility criteria. The main analysis compared combination therapy with high-dose statin monotherapy in high-risk patients. Very-low-strength evidence showed that statin-ezetimibe (2 trials; n = 439) and statin-fibrate (1 trial; n = 166) combinations did not reduce mortality more than high-dose statin monotherapy. No trials compared the effect of combination therapy versus high-dose statin monotherapy on the incidence of myocardial infarction, stroke, or revascularization procedures. Two statin-ezetimibe trials (n = 295) demonstrated higher low-density lipoprotein cholesterol goal attainment with combination therapy (odds ratio, 7.21 [95% CI, 4.30 to 12.08]). Trials in lower-risk patients did not show a difference in mortality.
  
  
  CONCLUSIONS
  Studies were generally short, focused on surrogate outcomes, and were heterogeneous in the sample's risk for coronary disease. Few studies examined treatment combinations other than statin-ezetimibe.
  
  
  CONCLUSIONS
  Limited evidence suggests that combinations of lipid-lowering agents do not improve clinical outcomes more than high-dose statin monotherapy. Very-low-quality evidence favors statin-ezetimibe treatment for attainment of low-density lipoprotein cholesterol goals.
  
  
  BACKGROUND
  Agency for Healthcare Research and Quality.
authors.affiliation: University of Ottawa, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Institute, Ottawa, Ontario, Canada.
authors.forename: Mukul
authors.initials: M
authors.lastname: Sharma
authors.forename: Mohammed T
authors.initials: MT
authors.lastname: Ansari
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Abou-Setta
authors.forename: Karla
authors.initials: K
authors.lastname: Soares-Weiser
authors.forename: Teik Chye
authors.initials: TC
authors.lastname: Ooi
authors.forename: Margaret
authors.initials: M
authors.lastname: Sears
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Yazdi
authors.forename: Alexander
authors.initials: A
authors.lastname: Tsertsvadze
authors.forename: David
authors.initials: D
authors.lastname: Moher
mesh_terms: D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000517:prevention & control; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D055118:Medication Adherence; D009026:Mortality; D012307:Risk Factors
chemical_list: D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors