CORRESPONDENCE: LETTER TO THE EDITOR
Optimizing Clopidogrel Therapy Before Stent Implantation: Should Clinical Setting Be Taken Into Account?
Dániel Aradi, MD*,
András Vorobcsuk, MD and
András Komócsi, MD, PhD
* Heart Institute, University of Pécs, Department of Interventional Cardiology, 13 Ifjusag Street, Pécs, NA 7624, Hungary (Email: daniel_aradi{at}yahoo.com).
We read with great interest the recently published work of Bonello et al. (1) regarding the clinical benefits of adjusting the loading dose of clopidogrel prior to percutaneous coronary intervention (PCI) according to platelet reactivity index (PRI) of vasodilator-stimulated phosphoprotein assay. The study is brilliant to demonstrate that low response to clopidogrel (defined as a PRI >50% in vasodilator-stimulated phosphoprotein assessment) increases the risk of cardiovascular death and recurrent ischemia. Moreover, repeated loading doses were successful in 86% of patients to overcome high PRI that translated to better clinical outcomes. However, for the following reasons, implementation of these findings to clinical practice is unclear.
The study cohort comprised a mixed population of 46% non–ST-segment elevation myocardial infarction (NSTEMI) and 54% nonacute coronary syndrome patients. Results of previous studies demonstrated that the net clinical benefit of intensifying platelet inhibition during PCI is highly different between patients of NSTEMI and stable angina. Likewise, neither clopidogrel pre-treatment nor administration of glycoprotein IIb/IIIa inhibitors (GPI) reduced ischemic complications among troponin-negative patients scheduled for elective PCI (2,3). Contrarily, patients admitted with NSTEMI for primary PCI had significantly lower rates of major adverse cardiac events in cases of GPI administration and clopidogrel pre-treatment (4,5). Based on these studies, it would be essential to know whether the clinical advantages shown in the study were driven by the troponin-positive NSTEMI population or whether stable angina patients also profited from the repeated loading doses. In a clinical aspect, there is no time limitation to optimize adenosine diphosphate-inhibition among stable angina patients before PCI; however, those admitted with NSTEMI might be harmed from delays in reperfusion while waiting for loading doses to overcome the low response to clopidogrel (6). As the latter patients might receive immediate GPI therapy to have proper platelet inhibition, waiting days for repeated loading doses does not seem the strategy of choice for them.
In conclusion, the landmark study of Bonello et al. (1) demonstrated in a mixed patient population that optimizing clopidogrel therapy according to a laboratory assay translates to significantly better short-term outcome after PCI. However, it is unclear how these results should affect current clinical practice. It seems highly important to separate low-risk stable angina and NSTEMI patients to be able to draw clear clinical consequences for the best antiplatelet strategy before PCI.
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- Bonello L, Camoin-Jau L, Arques S, et al. Adjusted clopidogrel loading doses according to vasodilator-stimulated phosphoprotein phosphorylation index decrease rate of major adverse cardiovascular events in patients with clopidogrel resistance: a multicenter randomized prospective study J Am Coll Cardiol 2008;51:1404-1411.[Abstract/Free Full Text]
- Widimsky P, Motovská Z, Simek S, et al. Clopidogrel pre-treatment in stable angina: for all patients >6 h before elective coronary angiography or only for angiographically selected patients a few minutes before PCI?. A randomized multicentre trial PRAGUE-8. Eur Heart J 2008Apr 25 [E-pub ahead of print].[Abstract/Free Full Text]
- Schömig A, Schmitt C, Dibra A, et al. One year outcomes with abciximab vs. placebo during percutaneous coronary intervention after pre-treatment with clopidogrel Eur Heart J 2005;26:1379-1384.[Abstract/Free Full Text]
- Iijima R, Ndrepepa G, Mehilli JJ, et al. Troponin level and efficacy of abciximab in patients with acute coronary syndromes undergoing early intervention after clopidogrel pretreatment Clin Res Cardiol 2008;97160–8.[CrossRef][ISI][Medline]
- Mehta SR, Yusuf S, Peters RJ, et al. , for Clopidogrel in Unstable angina to prevent Recurrent Events trial (CURE) Investigators. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001;358:527-533.[CrossRef][ISI][Medline]
- Neumann FJ, Kastrati A, Pogatsa-Murray G, et al. Evaluation of prolonged antithrombotic pretreatment ("cooling-off" strategy) before intervention in patients with unstable coronary syndromes: a randomized controlled trial JAMA 2003;290:1593-1599.[Abstract/Free Full Text]
Related Article
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Reply
- Laurent Bonello, Laurence Camoin-Jau, Arques Stephane, Paul Barragan, Francoise Dignat-George, and Franck Paganelli
J. Am. Coll. Cardiol. 2008 52: 1349-1350.
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