CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Laurent Bonello, MD*,
Laurence Camoin-Jau, MD, PhD,
Stéphane Arques, MD,
Paul Barragan, MD,
Francoise Dignat-George, PhD and
Franck Paganelli, MD
* Département de Cardiologie, Hôpital Universitaire Nord, Chemin des Bourrely, 13015, Marseille, France (Email: laurentbonello{at}yahoo.fr).
We thank Dr. Cuisset and colleagues for their critical review of our study (1). Many studies have suggested a stepwise relationship between platelet reactivity (PR) and ischemic recurrences after percutaneous coronary intervention (PCI), and the vasodilator-stimulated phosphoprotein index has been used extensively used in these trials. The threshold used to define low response in the present study was chosen according to its clinical and biological relevance (2–5). Further, this cut-off value exhibits a very high negative predictive value and a low positive predictive value, which illustrate the fact that, although ischemic recurrences are multifactorial, PR plays a key role.
Dr. Cuisset and colleagues seem to misunderstand available data on PR and the hypothesis tested in our study. The interindividual variability observed between patients in response to clopidogrel means that the effect of a 2,400-mg loading dose for low responders is inferior to that of 600 mg for good responders! Indeed, available data support the fact that the response to the drug, and not the dose, determines the outcome.
Finally, Dr. Cuisset and colleagues question the relevance of the present study with regard to the future marketing of prasugrel. The present trial is a landmark study demonstrating that PR is a modifiable risk factor for recurrent ischemic events and therefore of major interest not only for clopidogrel but for all other antiplatelet therapies that will be developed. Further, consistent with our results, researchers from the TRITON–TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis In Myocardial Infarction) study observed that greater PR inhibition, as achieved by prasugrel, compared with standard clopidogrel therapy, resulted in lower rates of ischemic events in patients undergoing PCI for acute coronary syndromes (6). However, achieving 90% PR inhibition with prasugrel resulted in a significant increase in major bleedings. Accordingly, the authors do not support the use of prasugrel for large subgroups of patients, including the elderly, those patients of low weight, those patients with previous stroke, and those patients undergoing elective PCI, which make up more than half of our patients. In addition, finding a threshold of PR to decrease ischemic events could be of great interest for the new P2Y12 ADP-receptor inhibitors to increase their risk/benefit ratio. Until prasugrel is available, platelet monitoring of the response to clopidogrel carries a potential clinical benefit for patients undergoing PCI. We believe that it is never too late to improve both our practice and patient outcomes.
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1. 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]2. Barragan P, Bouvier JL, Roquebert PO, et al. Resistance to thienopyridines: clinical detection of coronary stent thrombosis by monitoring of vasodilator-stimulated phosphoprotein phosphorylation Catheter Cardiovasc Interv 2003;59:295-302.[CrossRef][Web of Science][Medline] 3. Blindt R, Stellbrink K, de Taeye A, et al. The significance of vasodilator-stimulated phosphoprotein for risk stratification of stent thrombosis Thromb Haemost 2007;98:1329-1334.[Web of Science][Medline] 4. Schumacher WA, Bostwick JS, Ogletree ML, et al. Biomarker optimization to track the antithrombotic and hemostatic effects of clopidogrel in rats J Pharmacol Exp Ther 2007;322:369-377.[Abstract/Free Full Text] 5. Price MJ, Endemann S, Gollapudi RR, et al. Prognostic significance of post-clopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drug-eluting stent implantation Eur Heart J 2008;29:992-1000.[Abstract/Free Full Text] 6. TRITON-TIMI 38 Investigators Prasugrel versus clopidogrel in patients with acute coronary syndromes N Engl J Med 2007;357:2001-2015.[Abstract/Free Full Text]
Related Article
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Adjusting Clopidogrel Loading Doses According to Vasodilator-Stimulated Phosphoprotein Index: On Time, Too Early, or Too Late?
- Thomas Cuisset, Corinne Frere, Jacques Quilici, Marie Christine Alessi, and Jean Louis Bonnet
J. Am. Coll. Cardiol. 2008 52: 790-791.
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