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What accounts for the higher clinical efficacy of intracoronary abciximab?
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Letters to the Editor
What accounts for the higher clinical efficacy of intracoronary abciximab? Salvatore De Rosa, Gianluca Caiazzo, Daniele Torella, Ciro Indolfi ⁎ Division of Cardiology, “Magna Graecia” University of Catanzaro, Italy
a r t i c l e
i n f o
Article history: Received 22 April 2013 Accepted 4 May 2013 Available online 25 May 2013 Keywords: Intracoronary Abciximab Acute coronary syndrome
To the Editor: We truly appreciate the interesting comment by DominguezRodriguez et al. [1], in relation to our recently published metaanalysis comparing intracoronary and intravenous abciximab administration in patients with acute coronary syndrome [2], where they suggest local anti-inflammatory properties as an additional potential mechanism to explain the advantage observed with intracoronary abciximab administration [1]. Although intriguing, the evaluation of the mechanisms responsible for the clinical advantage observed with intracoronary abciximab administration in comparison to the intravenous route was beyond the aim of our work. Our aim was to review and summarize the body of evidence on the clinical benefit of intracoronary abciximab administration over the usual intravenous route. Nevertheless, we agree with Dominguez-Rodriguez et al. on the interest on such issue. Giving its short plasma half-life, standard intravenous abciximab administration might be inadequate to reach an effective concentration within the culprit vessel while direct intracoronary administration can warrant an acutely higher local concentration before dilution within the systemic circulation. Supporting this hypothesis, a recent study showed a higher degree of GP IIb/IIIa receptor occupancy, together with a more effective platelet inhibition after intracoronary administration as compared to intravenous administration [3]. In addition, DominguezRodriguez et al. showed that intracoronary abciximab administration is associated to a larger reduction in soluble CD40 ligand (sCD40L) levels compared to intravenous administration [4]. In line with this concept, the IC ClearLy trial was designed to test the hypothesis that direct abciximab administration into the culprit lesion through a dedicated ballooncatheter could foster clot resolution and improve myocardial perfusion as compared to intravenous administration [5].
⁎ Corresponding author at: Division of Cardiology and Department of Medical and Surgical Sciences, Magna Graecia University, Campus “S. Venuta”, Viale Europa (Germaneto), 88100 Catanzaro, Italy. Tel.: +39 09613647151; fax: +39 09613647153. E-mail address: indolfi@unicz.it (C. Indolfi). 0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.05.033
Indeed, local direct administration into the culprit vessel could facilitate both the anti-thrombotic and the non-GP IIb/IIIa-dependent properties of abciximab which, in contrast to other GP IIb/IIIa inhibitors, binds to vitronectine receptor on endothelial, smooth muscle and inflammatory cells [6]. In addition, abciximab also exerts indirect anticoagulant properties, inhibiting platelet-mediated tissue factor activation [7], a key pathophysiological event in the development of acute coronary syndromes [8]. Also interestingly, Marzilli et al. demonstrated that abciximab has a beneficial effect on coronary microcirculation [9]. Furthermore, a number of additional intriguing yet hypothetical mechanisms have been proposed to explain the major effectiveness of intracoronarily administered abciximab [10]. In conclusion, the higher local concentration reached after intracoronary abciximab, with consequent augmentation of both GP IIb/IIIa-dependent and -independent effects within the culprit vessel could be responsible for the observed higher clinical efficacy. References [1] Dominguez-Rodriguez A, Avanzas P, Abreu-Gonzalez P. Intracoronary abciximab and local anti-inflammatory effects. Int J Cardiol 2013;168(3):2872. [2] De Rosa S, Caiazzo G, Torella D, et al. Intracoronary abciximab reduces death and major adverse cardiovascular events in acute coronary syndromes: a meta-analysis of clinical trials. Int J Cardiol 2013;168(2):1298–305. [3] Desch S, Siegemund A, Scholz U, et al. Platelet inhibition and GP IIb/IIIa receptor occupancy by intracoronary versus intravenous bolus administration of abciximab in patients with ST elevation myocardial infarction. Clin Res Cardiol 2012;101:117–24. [4] Dominguez-Rodriguez A, Abreu-Gonzalez P, Avanzas P, et al. Intracoronary versus intravenous abciximab administration in patients with ST-elevation myocardial infarction undergoing thrombus aspiration during primary percutaneous coronary intervention — effects on soluble CD40 ligand concentrations. Atherosclerosis 2009;206:523–7. [5] Sardella G, Sangiorgi GM, Mancone M, et al. A multicenter randomized study to evaluate intracoronary abciximab with the ClearWay catheter to improve outcomes with Lysis (IC ClearLy): trial study design and rationale. J Cardiovasc Med (Hagerstown) Jul 2010;11(7):529–35. [6] Larson RS, Springer TA. Structure and function of leukocyte integrins. Immunol Rev Apr 1990;114:181–217. [7] Reverter JC, Béguin S, Kessels H, Kumar R, Hemker HC, Coller BS. Inhibition of platelet-mediated, tissue factor-induced thrombin generation by the mouse/human chimeric 7E3 antibody. Potential implications for the effect of c7E3 Fab treatment on acute thrombosis and “clinical restenosis”. J Clin Invest Aug 1 1996;98(3):863–74. [8] Golino P, Forte L, De Rosa S. Inhibition of the tissue factor coagulation pathway. Curr Vasc Pharmacol Oct 2004;2(4):319–27. [9] Marzilli M, Sambuceti G, Testa R, Fedele S. Platelet glycoprotein IIb/IIIa receptor blockade and coronary resistance in unstable angina. J Am Coll Cardiol Dec 18 2002;40(12):2102–9. [10] Romagnoli E, Burzotta F, Trani C, Biondi-Zoccai GG, Giannico F, Crea F. Rationale for intracoronary administration of abciximab. J Thromb Thrombolysis Feb 2007;23(1):57–63.
Letters to the Editor
What accounts for the higher clinical efficacy of intracoronary abciximab? Salvatore De Rosa, Gianluca Caiazzo, Daniele Torella, Ciro Indolfi ⁎ Division of Cardiology, “Magna Graecia” University of Catanzaro, Italy
a r t i c l e
i n f o
Article history: Received 22 April 2013 Accepted 4 May 2013 Available online 25 May 2013 Keywords: Intracoronary Abciximab Acute coronary syndrome
To the Editor: We truly appreciate the interesting comment by DominguezRodriguez et al. [1], in relation to our recently published metaanalysis comparing intracoronary and intravenous abciximab administration in patients with acute coronary syndrome [2], where they suggest local anti-inflammatory properties as an additional potential mechanism to explain the advantage observed with intracoronary abciximab administration [1]. Although intriguing, the evaluation of the mechanisms responsible for the clinical advantage observed with intracoronary abciximab administration in comparison to the intravenous route was beyond the aim of our work. Our aim was to review and summarize the body of evidence on the clinical benefit of intracoronary abciximab administration over the usual intravenous route. Nevertheless, we agree with Dominguez-Rodriguez et al. on the interest on such issue. Giving its short plasma half-life, standard intravenous abciximab administration might be inadequate to reach an effective concentration within the culprit vessel while direct intracoronary administration can warrant an acutely higher local concentration before dilution within the systemic circulation. Supporting this hypothesis, a recent study showed a higher degree of GP IIb/IIIa receptor occupancy, together with a more effective platelet inhibition after intracoronary administration as compared to intravenous administration [3]. In addition, DominguezRodriguez et al. showed that intracoronary abciximab administration is associated to a larger reduction in soluble CD40 ligand (sCD40L) levels compared to intravenous administration [4]. In line with this concept, the IC ClearLy trial was designed to test the hypothesis that direct abciximab administration into the culprit lesion through a dedicated ballooncatheter could foster clot resolution and improve myocardial perfusion as compared to intravenous administration [5].
⁎ Corresponding author at: Division of Cardiology and Department of Medical and Surgical Sciences, Magna Graecia University, Campus “S. Venuta”, Viale Europa (Germaneto), 88100 Catanzaro, Italy. Tel.: +39 09613647151; fax: +39 09613647153. E-mail address: indolfi@unicz.it (C. Indolfi). 0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.05.033
Indeed, local direct administration into the culprit vessel could facilitate both the anti-thrombotic and the non-GP IIb/IIIa-dependent properties of abciximab which, in contrast to other GP IIb/IIIa inhibitors, binds to vitronectine receptor on endothelial, smooth muscle and inflammatory cells [6]. In addition, abciximab also exerts indirect anticoagulant properties, inhibiting platelet-mediated tissue factor activation [7], a key pathophysiological event in the development of acute coronary syndromes [8]. Also interestingly, Marzilli et al. demonstrated that abciximab has a beneficial effect on coronary microcirculation [9]. Furthermore, a number of additional intriguing yet hypothetical mechanisms have been proposed to explain the major effectiveness of intracoronarily administered abciximab [10]. In conclusion, the higher local concentration reached after intracoronary abciximab, with consequent augmentation of both GP IIb/IIIa-dependent and -independent effects within the culprit vessel could be responsible for the observed higher clinical efficacy. References [1] Dominguez-Rodriguez A, Avanzas P, Abreu-Gonzalez P. Intracoronary abciximab and local anti-inflammatory effects. Int J Cardiol 2013;168(3):2872. [2] De Rosa S, Caiazzo G, Torella D, et al. Intracoronary abciximab reduces death and major adverse cardiovascular events in acute coronary syndromes: a meta-analysis of clinical trials. Int J Cardiol 2013;168(2):1298–305. [3] Desch S, Siegemund A, Scholz U, et al. Platelet inhibition and GP IIb/IIIa receptor occupancy by intracoronary versus intravenous bolus administration of abciximab in patients with ST elevation myocardial infarction. Clin Res Cardiol 2012;101:117–24. [4] Dominguez-Rodriguez A, Abreu-Gonzalez P, Avanzas P, et al. Intracoronary versus intravenous abciximab administration in patients with ST-elevation myocardial infarction undergoing thrombus aspiration during primary percutaneous coronary intervention — effects on soluble CD40 ligand concentrations. Atherosclerosis 2009;206:523–7. [5] Sardella G, Sangiorgi GM, Mancone M, et al. A multicenter randomized study to evaluate intracoronary abciximab with the ClearWay catheter to improve outcomes with Lysis (IC ClearLy): trial study design and rationale. J Cardiovasc Med (Hagerstown) Jul 2010;11(7):529–35. [6] Larson RS, Springer TA. Structure and function of leukocyte integrins. Immunol Rev Apr 1990;114:181–217. [7] Reverter JC, Béguin S, Kessels H, Kumar R, Hemker HC, Coller BS. Inhibition of platelet-mediated, tissue factor-induced thrombin generation by the mouse/human chimeric 7E3 antibody. Potential implications for the effect of c7E3 Fab treatment on acute thrombosis and “clinical restenosis”. J Clin Invest Aug 1 1996;98(3):863–74. [8] Golino P, Forte L, De Rosa S. Inhibition of the tissue factor coagulation pathway. Curr Vasc Pharmacol Oct 2004;2(4):319–27. [9] Marzilli M, Sambuceti G, Testa R, Fedele S. Platelet glycoprotein IIb/IIIa receptor blockade and coronary resistance in unstable angina. J Am Coll Cardiol Dec 18 2002;40(12):2102–9. [10] Romagnoli E, Burzotta F, Trani C, Biondi-Zoccai GG, Giannico F, Crea F. Rationale for intracoronary administration of abciximab. J Thromb Thrombolysis Feb 2007;23(1):57–63.