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CLINICAL RESEARCH: INTERVENTIONAL CARDIOLOGY

Mortality risk conferred by small elevations of creatine kinase-MB isoenzyme after percutaneous coronary intervention

John P. A. Ioannidis, MD^*,*, Evangelia Karvouni, MD and Demosthenes G. Katritsis, MD, PhD, FACC

^* Clinical Trials and Evidence-Based Medicine Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine and the Biomedical Research Institute, Foundation for Research and Technology, Hellas– Ioannina, Greece
Division of Clinical Care Research, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
Department of Cardiology, Athens Euroclinic, Athens, Greece

Manuscript received February 26, 2003; revised manuscript received April 4, 2003, accepted April 10, 2003.

^* Reprint requests and correspondence: Dr. John P. A. Ioannidis, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina 45110, Greece.
jioannid{at}cc.uoi.gr

OBJECTIVES: The aim of this study was to assess whether small creatine kinase-MB isoenzyme (CK-MB) elevations after percutaneous coronary intervention (PCI) affect the subsequent mortality risk.

BACKGROUND: Several studies have evaluated the relationship of CK-MB levels after PCI with the subsequent risk of death. While there is consensus that elevations exceeding 5 times the upper limit of normal increase mortality significantly, there is uncertainty about the exact clinical impact of smaller CK-MB elevations.

METHODS: We performed a meta-analysis of seven studies with CK-MB measurements and survival outcomes on 23,230 subjects who underwent PCI. Data were combined with random effects models.

RESULTS: Mean follow-up was 6 to 34 months per study. By random effects, 19% (95% confidence interval [CI], 16% to 23%) had one- to five-fold CK-MB elevations, while only 6% (95% CI, 5% to 9%) had >5-fold elevations. Compared with subjects with normal CK-MB, there was a dose-response relationship with relative risks for death being 1.5 (95% CI, 1.2 to 1.8, no between-study heterogeneity) with one- to three-fold CK-MB elevations, 1.8 (95% CI, 1.4 to 2.4, no between-study heterogeneity) with three- to five-fold CK-MB elevations, and 3.1 (95% CI, 2.3 to 4.2, borderline between-study heterogeneity) with over five-fold CK-MB elevations (p < 0.001 for all).

CONCLUSIONS: Any increase in CK-MB after PCI is associated with a small, but statistically and clinically significant, increase in the subsequent risk of death.

Abbreviations and Acronyms   CI = confidence interval   CK-MB = creatine kinase-MB isoenzyme   EPIC = Evaluation of IIb/IIIa Platelet Receptor Antagonist 7E3 in Preventing Ischemic Complications trial   EPILOG = Evaluation in PTCA to Improve Long-term Outcome with Abciximab Glycoprotein IIb/IIIa Blockade trial   IMPACT-II = Integrilin (eptifibatide) to Minimize Platelet Aggregation and Coronary Thrombosis-II study   PCI = percutaneous coronary intervention   PTCA = percutaneous transluminal coronary angioplasty

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