Elevated creatine kinase-MB with normal creatine kinase predicts worse outcomes in patients with acute coronary syndromes: results from 4 large clinical trials.
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.
Galla
John M
JM
Duke Clinical Research Institute, Durham, NC 27705, USA.
Mahaffey
Kenneth W
KW
Sapp
Shelly K
SK
Alexander
John H
JH
Roe
Matthew T
MT
Ohman
E Magnus
EM
Granger
Christopher B
CB
Armstrong
Paul W
PW
Harrington
Robert A
RA
White
Harvey D
HD
Simoons
Maarten L
ML
Newby
L Kristin
LK
Califf
Robert M
RM
Topol
Eric J
EJ
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
D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form