Elsevier

American Heart Journal

Volume 168, Issue 4, October 2014, Pages 503-511.e2
American Heart Journal

Clinical Investigation
Acute Ischemic Heart Disease
Prognostic implications of creatine kinase–MB measurements in ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention

https://doi.org/10.1016/j.ahj.2014.06.008Get rights and content

Background

Peak creatine kinase (CK)–MB concentration is related to reperfusion success and clinical outcomes after fibrinolytic therapy for acute myocardial infarction. However, prognostic implications of CK-MB measurements after primary percutaneous coronary intervention (PCI), which provides more predictable and consistent reperfusion, are unknown.

Methods

We pooled 2,042 primary PCI–treated ST-segment elevation myocardial infarction (STEMI) patients from 3 trials with serial core laboratory–determined CK-MB measurements; 1,799 patients (88.1%) who survived to 36 hours and had ≥4 CK-MB measurements were studied. Cox regression modeling was performed to quantify the association between peak CK-MB concentration (and area under the time-concentration curve [AUC]) and mortality at 6 months, and death or congestive heart failure at 90 days.

Results

The median (25th-75th percentiles) peak CK-MB concentration and AUC measurement through 36 hours were 239 (109-429) ng/mL and 4,263 (2,081-7,124) ng/(mL h), respectively. By multivariable analysis, peak CK-MB concentration and AUC measurement were independently associated with 6-month mortality (adjusted hazard ratio [HR] 1.15, 95% CI 1.05-1.25, per 100-ng/mL increase, P = .002; and adjusted HR 1.09, 95% CI 1.03-1.14, per 1,000-ng/[mL h] increase, P < .001, respectively) and 90-day death or congestive heart failure (adjusted HR 1.26, 95% CI 1.18-1.34, P < .001; and adjusted HR 1.15, 95% CI 1.11-1.19, P < .001, respectively).

Conclusions

Peak CK-MB concentration and AUC measurement are independent predictors of 3- to 6-month cardiovascular outcomes in primary PCI–treated STEMI patients. Our findings guide application of these measurements as efficacy end points in early-phase studies evaluating new therapies for STEMI.

Section snippets

Methods

We pooled 2,042 patients with STEMI who were treated with primary PCI within 6 hours of symptom onset and were enrolled in the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) (n = 814),8 Direct Inhibition of δ-Protein Kinase C Enzyme to Limit Total Infarct Size in Acute Myocardial Infarction (DELTA MI) (n = 154),9 and Inhibition of δ-Protein Kinase C for Reduction of Infarct Size in Acute Myocardial Infarction (PROTECTION-AMI) (n = 1,074) trials.10 The principal

Baseline demographics and angiographic features

Clinical characteristics and procedural findings of the overall study population stratified by the 3 included trials are shown in Table I. Overall, the median (25th-75th percentiles) age was 60 (52-70) years, and 22.1% patients were female; 12.0% had a prior history of MI. The median total ischemic time was 3.2 (2.4-4.4) hours, 82.3% of patients had an anteriorly located infarction, and 98.3% were Killip class I/II on presentation. At baseline, 69.0% had TIMI flow grade 0/1 in the

Discussion

In this pooled analysis of nearly 1,800 STEMI patients treated with primary PCI with serial core laboratory–determined CK-MB measurements, both peak CK-MB concentration and AUC measurements were independently associated with death or CHF occurring within 90 days and mortality occurring within 6 months. There was no heterogeneity in the magnitude of this prognostic relationship by location of infarction. These findings can be used to guide the application of CK-MB release patterns as efficacy

Conclusions

In STEMI patients treated with primary PCI, both the peak CK-MB concentration and AUC measurement are associated with important 3- to 6-month cardiovascular outcomes independent of other clinical and angiographic characteristics. These findings guide application of CK-MB release patterns after primary PCI as efficacy end points in early-phase clinical trials evaluating new therapies for MI.

Sources of funding

This work was supported by no outside support, but instead was self-funded. The DELTA MI trial was funded by KAI Pharmaceuticals. The PROTECTION-AMI trial was funded by KAI Pharmaceuticals and Bristol-Myers Squibb. The COMMA trial was funded by Procter & Gamble Pharmaceuticals and Alexion Pharmaceuticals Inc.

Conflict of interest disclosures

A. Bagai: Dr Bagai has no relevant disclosures to report.

P.J. Schulte: Dr Schulte has no relevant disclosures to report.

C.B. Granger: Dr Granger received research support from Astellas Pharma US, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic Foundation, Merck & Co, Sanofi-Aventis, and The Medicines Company and consulting for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Hoffmann-La Roche, Novartis Pharmaceutical Company, Otsuka

Acknowledgements

We thank Peter Hoffmann for his editorial contributions to this manuscript. Mr Hoffmann did not receive compensation for his contributions apart from his employment at the institution where this study was conducted.

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Pamela N. Peterson, MD, MSPH, served as guest editor for this article.

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