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Methods of creatine kinase-MB analysis to predict mortality in patients with myocardial infarction treated with reperfusion therapy.

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Date
2013-05-02
Authors
Lopes, Renato D
Lokhnygina, Yuliya
Hasselblad, Victor
Newby, Kristin L
Yow, Eric
Granger, Christopher B
Armstrong, Paul W
Hochman, Judith S
Mills, James S
Ruzyllo, Witold
Mahaffey, Kenneth W
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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.
Type
Journal article
Subject
Area Under Curve
Biomarkers
Clinical Enzyme Tests
Creatine Kinase, MB Form
Heart Failure
Humans
Myocardial Infarction
Myocardial Reperfusion
Percutaneous Coronary Intervention
Predictive Value of Tests
Proportional Hazards Models
Risk Assessment
Risk Factors
Shock
Stroke
Thrombolytic Therapy
Time Factors
Treatment Outcome
Permalink
https://hdl.handle.net/10161/12499
Published Version (Please cite this version)
10.1186/1745-6215-14-123
Publication Info
Lopes, Renato D; Lokhnygina, Yuliya; Hasselblad, Victor; Newby, Kristin L; Yow, Eric; Granger, Christopher B; ... Mahaffey, Kenneth W (2013). Methods of creatine kinase-MB analysis to predict mortality in patients with myocardial infarction treated with reperfusion therapy. Trials, 14. pp. 123. 10.1186/1745-6215-14-123. Retrieved from https://hdl.handle.net/10161/12499.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Paul Wayne Armstrong

Adjunct Professor in the Department of Medicine
Granger

Christopher Bull Granger

Professor of Medicine
Research: My primary research interest is in conduct and methodology of large randomized clinical trials in heart disease. I have led a number of large international clinical studies in heart attacks, unstable angina, heart failure, and atrial fibrillation. I have lead clinical studies of blood thinners and coronary intervention for heart attacks, stroke prevention in atrial fibrillation, and prevention of heart attack for patients with coronary artery disease. I have been co-directo
Hasselblad

Victor Hasselblad

Professor Emeritus of Biostatistics & Bioinformatics
The research interests of Vic Hasselblad include distribution fitting, sample size and power calculations, dose-response estimation, meta-analysis, and non-inferiority designs.
Lokhnygina

Yuliya Vladimirovna Lokhnygina

Associate Professor of Biostatistics & Bioinformatics
Statistical methods in clinical trials, survival analysis, adaptive designs, adaptive treatment strategies, causal inference in observational studies, semiparametric inference
Lopes

Renato Delascio Lopes

Professor of Medicine
Atrial Fibrillation Antithrombotic Therapy in patients with Acute Coronary Syndromes Elderly patients with Heart Disease Biomarkers in Acute Coronary Syndromes and Atrial Fibrillation Thrombosis and Anticoagulation and novel antithrombotic agents Metabolomics in Cardiovascular Medicine
Mills

James Steven Mills

Assistant Professor of Medicine
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