CORRESPONDENCE: LETTER TO THE EDITOR
Exclusive Antiplatelet Therapy for Percutaneous Coronary Intervention
Scott J. Denardo, MD*
* Division of Cardiovascular Medicine, University of Florida, 1600 SW Archer Road, P.O. Box 100277, Gainesville, Florida 32610 (Email: scott.denardo{at}medicine.ufl.edu).
A journey of a thousand miles begins with a single step.
—Lao Tzu, ancient Chinese philosopher (1)
Stabile et al. (2) indeed deserve congratulations for the clinical trial that they recently published in the Journal. It is the first step on a journey into exclusive dual antiplatelet therapy (aspirin and clopidogrel) alone during percutaneous coronary intervention (PCI), without scheduled antithrombin or glycoprotein inhibitor therapy. However, as pointed out in the accompanying editorial by Dauerman (3), there are several concerns with the trial. Specifically, the approach of dual antiplatelet therapy alone may lack an essential "safety net" that could be provided by antithrombin therapy or, perhaps, glycoprotein inhibitor therapy.
Thrombosis during PCI and otherwise occurs through 2 inter-related mechanisms: first, the adhesion, activation, secretion, and aggregation of platelets; and second, amplification of the coagulation cascade, which requires an activated platelet surface for the development of thrombin (4). In theory, if adequate antiplatelet therapy is provided, thrombosis will not occur, even in the absence of antithrombin therapy directed towards the coagulation cascade. This theory has been supported by in vitro experiments dating back over 20 years (5).
Subsequent clinical research published 15 years ago involving a new class of drug, the glycoprotein IIb/IIIa inhibitors (e.g., abciximab), which block the final common pathway of platelet aggregation, showed a significant decrease in ischemic complications during PCI at the expense of a significant increase in bleeding complications (6). These results created a dilemma for those interventional cardiologists (including myself) who already had a relatively high bleeding complication rate (7). Therefore, 12 years ago, in an effort to optimize patient care, I changed from the then contemporary combination of dual antiplatelet therapy (aspirin and ticlopidine) and a conventional dose of unfractionated heparin to triple antiplatelet therapy (adding abciximab) and only a minimal dose of unfractionated heparin. The success of this approach (8) led me to take one step further 9 years ago to exclude scheduled antithrombin therapy altogether for both elective, low risk and urgent, higher risk PCI, while relying on triple antiplatelet therapy (aspirin, clopidogrel, and eptifibatide) alone (9,10). Despite the success of this strategy in limiting both ischemic and bleeding complications, and despite subsequent support provided by REMOVE (Reduction in Major and Minor Adverse Events With Eptifibatide-based Pharmacotherapy in Percutaneous Coronary Intervention) (11), exclusive antiplatelet therapy drew skepticism and criticism from many of our cardiovascular colleagues. The trial published by Stabile et al. (2) therefore provided timely and much needed support for the "exclusive antiplatelet therapy" proponents.
Stabile et al. (2), however, was confined to very low-risk PCI, and the safety net concern expressed by Dauerman (3) poses a valid question. On the basis of theory, in vitro experiments and my own experiences, I believe that the safety net can be provided by glycoprotein IIb/IIIa receptor inhibition, using abciximab, eptifibatide, or, perhaps, tirofiban. This approach of triple antiplatelet therapy with minimal or no specific antithrombin therapy directed towards the coagulation cascade during PCI will, in my opinion, prove to be safe and efficacious for both elective, low-risk and urgent, higher-risk PCI. Hopefully, this approach will be proved by unbiased, well-designed randomized clinical trials that continue the journeys initiated by the proponents of "exclusive antiplatelet therapy" during PCI, including Stabile et al. (2)
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1. Sayings and Quotes http://www.sayingsnquotes.com/quotations-by-subject/beginning-quotes-and-sayings/Accessed October 29, 2008.2. 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. Stein B, Fuster V, Israel DH, et al. Platelet inhibitor agents in cardiovascular disease: an update J Am Coll Cardiol 1989;14:813-836.[Abstract] 5. Rosing J, van Rijn JL, Bevers EM, van Dieijen G, Comfurius P, Zwaal RF. The role of activated human platelets in prothrombin and factor X activation Blood 1985;65:319-332.[Abstract/Free Full Text] 6. The EPIC Investigators Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty N Engl J Med 1994;330:956-961.[Abstract/Free Full Text] 7. Denardo SJ, Davis KE, Reid PR, Tcheng JE. Minimal dose heparin with abciximab in coronary intervention: efficacy and safety of a novel heparin dosing strategyIn: Lewis BS, editor. Advances in Coronary Artery Disease: Proceedings of the 4th International Congress on Coronary Artery Disease: Prague, Czech Republic, October 21–24, 2001. Bologna, Italy: Monduzzi Editore; 2001. pp. 573-578. 8. Denardo SJ, Davis KE, Reid PR, Tcheng JE. Efficacy and safety of minimal dose ( 1000 Unit) unfractionated heparin with abciximab in percutaneous coronary intervention Am J Cardiol 2003;91:1-5.[Web of Science][Medline] 9. Denardo SJ, Davis KE, Tcheng JE. Elective percutaneous coronary intervention using broad-spectrum antiplatelet therapy (eptifibatide, clopidogrel, and aspirin) alone, without scheduled unfractionated heparin or other anti-thrombin therapy Am Heart J 2005;149:138-144.[CrossRef][Web of Science][Medline] 10. Denardo SJ, Davis KE, Tcheng JE. Reduced-dose enoxaparin in non-ST segment elevation acute coronary syndrome, followed by antiplatelet therapy alone during subsequent percutaneous coronary intervention Am J Cardiol 2007;100:1376-1382.[CrossRef][Web of Science][Medline] 11. 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]
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