CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Allan M. Ross, MD, FACC,
Raymond J. Gibbons, MD, FACC,
Gregg W. Stone, MD, FACC,
Robert A. Kloner, MD, PhD, FACC and
R. Wayne Alexander, MD, PhD, FACC
Department of Medicine, Emory University Hospital, H-153, 1364 Clifton Road NE, Atlanta, Georgia 30322
We thank Drs. Cohen and Downey for their interest in our report on treatment of anterior myocardial infarction with adenosine (1). We do not agree that we misquoted Yao and Gross (2) and Thornton et al. (3) with respect to the cardioprotective effects of adenosine. The Thornton et al. study was cited, with others, in stating that "adenosine has consistently provided myocardial protection from ischemic injury." The Yao and Gross study (2) supports the statement that "adenosine and adenosine agonists are myocardial protectants." We did not say that this protection was specifically related to the time of reperfusion, as implied. The reduction in infarct size may have been related also to other salutary effects of adenosine. In many patients the drug was on board during at least part of the time of coronary occlusion, and thus it might have a protective effect during ischemia. Certainly, in those receiving thrombolytic therapy, there was a time lag between administration of the lytic and when reperfusion was complete. Thus, it is possible that adenosine played a protective role during this time of continuing ischemia.
We do not agree that the difference in infarct size in the AMISTAD I and AMISTAD II studies somehow imputes the reliability of the single-photon emission computed tomography data in the AMISTAD II study. The validity of SPECT infarct size measurement is well-established (4) on the basis of multiple lines of scientific evidence. We agree that myocardium at risk is highly variable and a major determinant of infarct size in both animal models and humans. The absence of measurement of myocardium at risk will reduce power (i.e., increase the likelihood of a type II [beta] statistical error). However, the estimates reported in our paper of a type I (alpha) statistical error for infarct size remain valid. In the AMISTAD I study (5), myocardium at risk was measured in a subset of patients. In anterior infarcts, adenosine showed similar benefit using either myocardial salvage index (p = 0.015) or infarct size (p = 0.014). Other randomized trials that have measured myocardium at risk and infarct size (6,7) have reported similar significant differences using either infarct size or salvage index as an end point.
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1. Ross AM, Gibbons RJ, Stone GW, Kloner RA, Alexander RW. A randomized, double-blinded placebo-controlled multicenter trial of adenosine as an adjunct to reperfusion in the treatment of acute myocardial infarction (AMISTAD-II) J Am Coll Cardiol 2005;45:1775-1780.[Abstract/Free Full Text]2. Yao Z, Gross GJ. A comparison of adenosine-induced cardioprotection and ischemic preconditioning in dogsefficacy, time course, and role of KATP channels. Circulation 1994;89:1229-1236.[Abstract/Free Full Text] 3. Thornton JD, Liu GS, Olsson, RA, Downey JM. Intravenous pretreatment with A1-selective adenosine analogues protects the heart against infarction Circulation 1992;85:659-665.[Abstract/Free Full Text] 4. Gibbons RJ, Valeti US, Araoz PA. The quantification of infarct size J Am Coll Cardiol 2004;44:1533-1542.[Abstract/Free Full Text] 5. Mahaffey KW, Puma JA, Barbagelata NA. Adenosine as an adjunct to thrombolytic therapy for acute myocardial infarction: results of a multicenter, randomized, placebo-controlled trial: the Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial J Am Coll Cardiol 1999;34:1711-1720.[Abstract/Free Full Text] 6. Schomig A, Katrati A, Dirshinger J. Coronary stenting plus platelet glycoprotein IIb/IIIa blockade compared with tissue plasminogen activator in acute myocardial infarction N Engl J Med 2000;343:385-391.[Abstract/Free Full Text] 7. Kastrati A, Mehilli J, Dirshinger J. Myocardial salvage after coronary stenting plus abciximab versus fibrinolysis plus abciximab in patients with acute myocardial infarctiona randomized trial. Lancet 2002;359:920-925.[CrossRef][Web of Science][Medline]
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