title: Elevated creatine kinase-MB with normal creatine kinase predicts worse outcomes in patients with acute coronary syndromes: results from 4 large clinical trials.
abstract: BACKGROUND
  The degree to which elevated creatine kinase (CK)-MB in the presence of normal CK is predictive of outcome is not well understood despite having been studied for decades. This analysis examined whether normal CK with elevated CK-MB in patients with non-ST-segment elevation acute coronary syndrome (NSTE ACS) is an independent predictor of worse outcomes. A concomitant goal was to contribute insight to the debate over how patients with NSTE ACS should be managed.
  
  
  METHODS
  Data for 25,960 patients from the GUSTO IIb, PARAGON A and B, and PURSUIT trials were analyzed. Of these patients, 6402 were excluded from primary analysis because of missing (unmeasured) biomarkers. Patients with complete laboratory data (n = 19,558) were grouped by CK and CK-MB results. To confirm the primary analysis results, data from patients with missing biomarkers were used in an imputation model.
  
  
  RESULTS
  Patients were categorized in 1 of 4 groups: normal CK + normal CK-MB; normal CK + elevated CK-MB; elevated CK + normal CK-MB; or elevated CK + elevated CK-MB. For the primary outcome, 180-day death, or myocardial infarction, Kaplan-Meier estimates were 14.9%, 20.8%, 14.5%, and 18.2%, respectively. Regardless of total CK, elevated CK-MB was associated with a 25% to 49% increased relative risk of worse outcomes. Findings from the analyses were verified by the multivariable model.
  
  
  CONCLUSIONS
  CK-MB remains a reliable marker for myocardial necrosis and a strong predictor of worse prognosis. All patients with ACS should have CK-MB measurement to search for cardiac ischemia. Patients with elevated CK-MB should receive aggressive management commensurate with their increased risks.
authors.affiliation: Duke Clinical Research Institute, Durham, NC 27705, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Galla
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.forename: Shelly K
authors.initials: SK
authors.lastname: Sapp
authors.forename: John H
authors.initials: JH
authors.lastname: Alexander
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Roe
authors.forename: E Magnus
authors.initials: EM
authors.lastname: Ohman
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.forename: Maarten L
authors.initials: ML
authors.lastname: Simoons
authors.forename: L Kristin
authors.initials: LK
authors.lastname: Newby
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Topol
mesh_terms: D000208:Acute Disease; D000368:Aged; D000789:Angina, Unstable / Q000097:blood* / Q000188:drug therapy / Q000401:mortality*; D002986:Clinical Trials as Topic; D003402:Creatine Kinase / Q000097:blood; D052279:Creatine Kinase, MB Form / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000188:drug therapy / Q000401:mortality*; D011237:Predictive Value of Tests; D011379:Prognosis; D013577:Syndrome
chemical_list: D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form