CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Allen Jeremias, MD,
Donald S. Baim, MD, FACC,
Richard E. Kuntz, MD, MSc, FACC and
Donald E. Cutlip, MD, FACC*
* Interventional Cardiology Section, Beth Israel Deaconess Medical Center, 185 Pilgrim Road, Baker 4, Boston, MA 02215 (Email: dcutlip{at}bidmc.harvard.edu).
We thank Dr. Ioannidis and colleagues for their interest in our study (1), in which we hypothesized that procedure success would have a significant effect on the reported association between mortality and peri-procedural creatine kinase-MB fraction (CK-MB) elevation. Dr. Ioannidis and colleagues have raised concerns regarding insufficient numbers of patients and events to adequately address the question, justification for pooling of the clinical trial data, interpretation of the small absolute risk difference, and a definition of procedure success that is not standardized in the published data.
These same investigators have published a meta-analysis of 23,230 patients (including ACS [acute coronary syndrome] and vein graft interventions) treated by a mixture of stent, directional coronary atherectomy, and balloon angioplasty over a decade, showing a one-year mortality risk of 3.5% with normal CK-MB, rising to 5.2%, 6.3%, and 10.9% for CK-MB 1 to 3, 3 to 5, and >5 times normal, respectively (2). What such meta-analyses gain in numbers of patients and events may be lost in lack of detail about those patients—for instance, whether the effect holds true for stenting (as used in 90% of current interventions), and whether it applies equally to incidental CK-MB elevations seen after otherwise successful procedures. Our study is actually one of the largest reports after elective stenting, with nearly 6,000 patients and over 100 death events, and includes data pooled at the patient-by-patient level, so that it could look into the question with greater granularity. The pooling of the trials was fully justified based on the nearly identical inclusion criteria and baseline clinical and angiographic characteristics (3,4). The one-year mortality was similar to other elective stent populations (5) and was essentially flat for normal-to-moderate level CK-MB elevations among successful procedures, whereas mortality was over six times higher in patients with unsuccessful procedures and any elevation in CK-MB.
As we stated in our discussion, the 0.4% absolute difference in mortality between patients with and without myocardial infarction (MI) after successful intervention could still be clinically meaningful. But we must reject the other criticisms of Dr. Ioannidis and colleagues regarding the limitations of our study. The inferences are not based on a small number of unsuccessful procedures, but on an analysis of 5,850 patients with over 100 deaths, for which an unsuccessful procedure was one of the most significant independent predictors of one-year mortality. Most importantly, we are concerned with the misinterpretation of our identification of successful and unsuccessful procedures. We were careful to select unsuccessful procedures using criteria on which most operators would concur in the context of current stenting techniques. We agree many would choose to broaden these criteria and thus further purify the successful group. Regardless of where this line of success is drawn, however, it is clear that the effect of CK-MB elevation among truly successful procedures in this patient cohort would be small to nonexistent.
We also agree that this finding is worth validating in larger numbers of patients. Doing so will require access to databases where the pre-procedure risk and results of successful and unsuccessful procedures are clearly identified, thereby avoiding unnecessary panic among patients and their physicians when small elevations in CK-MB are detected following an otherwise successful procedure.
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References
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1. Jeremias A, Baim DS, Ho KK, et al. Differential mortality risk of post procedural creatine kinase-MB elevation following successful versus unsuccessful stent procedures J Am Coll Cardiol 2004;44:1210-1214.[Abstract/Free Full Text]
2. Ioannidis JP, Karvouni E, Katritsis DG. Mortality risk conferred by small elevations of creatine kinase-MB isoenzyme after percutaneous coronary intervention J Am Coll Cardiol 2003;42:1406-1411.[Abstract/Free Full Text]
3. Cutlip DE, Baim DS, Ho KK, et al. Stent thrombosis in the modern eraa pooled analysis of multicenter coronary stent clinical trials. Circulation 2001;103:1967-1971.[Abstract/Free Full Text]
4. Cutlip DE, Chauhan MS, Baim DS, et al. Clinical restenosis after coronary stentingperspectives from multicenter clinical trials. J Am Coll Cardiol 2002;40:2082-2089.[Abstract/Free Full Text]
5. Topol EJ, Mark DB, Lincoff AM, et al. Outcomes at 1 year and economic implications of platelet glycoprotein IIb/IIIa blockade in patients undergoing coronary stenting: results from a multicentre randomised trial. EPISTENT investigators. Evaluation of Platelet IIb/IIIa Inhibitor for Stenting Lancet 1999;354:2019-2024.[CrossRef][Web of Science][Medline]
Related Article
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Creatine Kinase-MB Elevation Following Stent Implantation
- John P.A. Ioannidis, Evangelia Karvouni, and Demosthenes G. Katritsis
J. Am. Coll. Cardiol. 2005 45: 1908.
[Full Text]
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