CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Harold L. Dauerman, MD*
* University of Vermont College of Medicine, Fletcher Allen Health Care, 111 Colchester Avenue, McClure 1 Cardiology, Burlington, Vermont 05401 (Email: harold.dauerman{at}vtmednet.org).
Well some things you can explain away, but the heartache's in me till this day.
—The Clash, 1979 (1)
I read with interest Dr. Denardo's letter concerning the CIAO (Coronary Interventions Antiplatelet-based Only) trial (2) and the accompanying editorial (3). My congratulations are extended to Dr. Denardo and other investigators who have found novel approaches to reducing bleeding complications associated with percutaneous coronary intervention (PCI), including the CIAO approach, fondaparinux, bivalirudin, reduced doses of unfractionated heparin, improved femoral access technique, or radial artery approaches. As discussed in the editorial (3), caution is warranted when data are limited to selected lower-risk patient subsets.
Dr. Denardo's letter, though, focuses congratulations on the CIAO trial as a "first step on a journey into exclusive dual antiplatelet therapy." As expressed in the editorial, there are pathophysiologic concerns about embarking on this journey in higher-risk subgroups of patients. Specifically, concern arises with the statement: "if adequate antiplatelet therapy is provided, thrombosis will not occur, even in the absence of antithrombin therapy. . . ." Arguments against this hypothesis are the following: - • During the REMOVE (Reduction in Major and Minor Adverse Events With Eptifibatide-based Pharmacotherapy in Percutaneous Coronary Intervention) trial, thrombus did form during bifurcation PCI despite aspirin, clopidogrel, and glycoprotein inhibition (GPI). Thus, the protocol was amended to exclude these higher-risk lesions from a no-antithrombin approach (4).
- • Platelet activation is induced by vessel injury, exposure to collagen, and a myriad of other agents. No antiplatelet agent that is clinically available can inhibit all pathways of platelet activation (5). Further, although GPI decreases platelet aggregation and the quantity of platelets in a growing thrombus, it may not prevent platelet adherence or platelet–leukocyte aggregation that can contribute to thrombin formation (6).
- • Nonplatelet blood elements, particularly monocytes, support thrombin generation (7). The exclusive antiplatelet therapy approach would not necessarily prevent nonplatelet-mediated generation of thrombin.
New approaches to PCI that will reduce bleeding complications and prevent thrombotic events are important. Although the first steps towards exclusive antiplatelet therapy indeed have been initiated, current understanding of the complex pathophysiology of thrombus generation cannot easily be explained away by the results to date; the risk for "heartache" without thrombin inhibition needs to be further investigated in broader trials of this concept.
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References
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1. The Clash. Train in Vain (song). On: London Calling (album). United Kingdom: Columbia Records, released December 1979.2. Stabile E, Nammas W, Salemme L, et al. The CIAO (Coronary Interventions Antiplatelet-based Only) study: a randomized study comparing standard anticoagulation regimen to absence of anticoagulation for elective percutaneous coronary intervention J Am Coll Cardiol 2008;52:1293-1298.[Abstract/Free Full Text] 3. Dauerman HL. Coronary intervention without a safety net J Am Coll Cardiol 2008;52:1299-1301.[Free Full Text] 4. Valencia R, Price MJ, Sawhney N, et al. Efficacy and safety of triple antiplatelet therapy with and without concomitant anticoagulation during elective percutaneous coronary intervention (the REMOVE trial) Am J Cardiol 2007;100:1099-1102.[CrossRef][Web of Science][Medline] 5. Offermanns S. Activation of platelet function through G protein-coupled receptors Circ Res 2006;99:1293-1304.[Abstract/Free Full Text] 6. Brambilla M, Camera M, Colnago D, et al. Tissue factor in patients with acute coronary syndromes: expression in platelets, leukocytes, and platelet-leukocyte aggregates Arterioscler Thromb Vasc Biol 2008;28:947-953.[Abstract/Free Full Text] 7. Roberts HR, Hoffman M, Monroe DM. A cell-based model of thrombin generation Semin Thromb Hemost 2006;32(Suppl 1):32-38.
Related Article
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Exclusive Antiplatelet Therapy for Percutaneous Coronary Intervention
- Scott J. Denardo
J. Am. Coll. Cardiol. 2009 53: 1921-1922.
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