title: Methods of creatine kinase-MB analysis to predict mortality in patients with myocardial infarction treated with reperfusion therapy.
abstract: BACKGROUND
  Larger infarct size measured by creatine kinase (CK)-MB release is associated with higher mortality and has been used as an important surrogate endpoint in the evaluation of new treatments for ST-segment elevation myocardial infarction (STEMI). Traditional approaches to quantify infarct size include the observed CK-MB peak and calculated CK-MB area under the curve (AUC). We evaluated alternative approaches to quantifying infarct size using CK-MB values, and the relationship between infarct size and clinical outcomes.
  
  
  METHODS
  Of 1,850 STEMI patients treated with reperfusion therapy in the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) (percutaneous coronary intervention (PCI)-treated) and the COMPlement inhibition in myocardial infarction treated with thromboLYtics (COMPLY) (fibrinolytic-treated) trials, 1,718 (92.9%) (COMMA, n = 868; COMPLY, n = 850) had at least five of nine protocol-required CK-MB measures. In addition to traditional methods, curve-fitting techniques were used to determine CK-MB AUC and estimated peak CK-MB. Cox proportional hazards modeling assessed the univariable associations between infarct size and mortality, and the composite of death, heart failure, shock and stroke at 90 days.
  
  
  RESULTS
  In COMPLY, CK-MB measures by all methods were significantly associated with higher mortality (hazard ratio range per 1,000 units increase: 1.09 to 1.13; hazard ratio range per 1 standard deviation increase: 1.41 to 1.62; P <0.01 for all analyses). In COMMA, the associations were similar but did not reach statistical significance. For the composite outcome of 90-day death, heart failure, shock and stroke, the associations with all CK-MB measures were statistically significant in both the COMMA and COMPLY trials.
  
  
  CONCLUSIONS
  Sophisticated curve modeling is an alternative to infarct-size quantification in STEMI patients, but it provides information similar to that of more traditional methods. Future studies will determine whether the same conclusion applies in circumstances other than STEMI, or to studies with different frequencies and patterns of CK-MB data collection.
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, 2400 Pratt Street, Room 0311, Terrace Level, Box 3850, Durham, NC 27705, USA. renato.lopes@duke.edu
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Lokhnygina
authors.forename: Victor
authors.initials: V
authors.lastname: Hasselblad
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Newby
authors.forename: Eric
authors.initials: E
authors.lastname: Yow
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
authors.forename: Judith S
authors.initials: JS
authors.lastname: Hochman
authors.forename: James S
authors.initials: JS
authors.lastname: Mills
authors.forename: Witold
authors.initials: W
authors.lastname: Ruzyllo
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
mesh_terms: D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D004796:Clinical Enzyme Tests / Q000379:methods*; D052279:Creatine Kinase, MB Form / Q000097:blood*; D006333:Heart Failure / Q000209:etiology / Q000401:mortality; D006801:Humans; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy*; D015425:Myocardial Reperfusion / Q000009:adverse effects / Q000401:mortality*; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects / Q000401:mortality*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D012769:Shock / Q000209:etiology / Q000401:mortality; D020521:Stroke / Q000209:etiology / Q000401:mortality; D015912:Thrombolytic Therapy / Q000009:adverse effects / Q000401:mortality*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D052279:Creatine Kinase, MB Form