Response to Letter Regarding Article, “Pathological Correlates of Late Drug-Eluting Stent Thrombosis: Strut Coverage as a Marker of Endothelialization”
We appreciate the interest shown by Dr Testa and colleagues regarding our article.1 First, we acknowledge the wide variation in duration of stent implantation in our samples. Unlike clinical trials, where large numbers of patients can be studied and followed up at regular intervals, the pathological samples presented in the article are referred to us and are both rare and impossible to obtain at regular intervals. To the best of our knowledge, ours is the largest registry of these samples. We chose the time point >30 days to coincide with the clinical definition of late stent thrombosis (LST) reported in registries and clinical studies.2–4 Just as in these studies, the timing of stent thrombosis varied widely.
In response to their second concern, Table 1 in our original article1 is correct. The misunderstanding relates to the fact that Table 1 represents the sum of patients taking each type of antiplatelet agent. As stated correctly in the text, antiplatelet therapy status was known for 18/23 cases (78%) in the LST group and for 14/23 patients (61%) in the patent group (Table 1). Eleven of 18 patients with LST (61%) and 5/14 with patent drug-eluting stents (36%) were on dual antiplatelet therapy. Four of 18 (22%) with LST and 2/14 with patent drug-eluting stents (14%) were on aspirin only, whereas 1/18 with LST (6%) and 1/14 with patent drug-eluting stents (7%) were only on clopidogrel. Two of 18 patients (11%) in the LST group and 6/14 patients (43%) in the patent drug-eluting stent group were not on antiplatelet therapy at the time of death. This means, for instance, that a total of 15 patients in the LST group were taking aspirin, as indicated in Table 1.
We agree that from our data we cannot make any conclusions about the use of antiplatelet therapy in the causation of stent thrombosis. Of course, it is possible that different pathological mechanisms are involved in stent thrombosis at 1 month and at 2 years. In fact, we have shown previously that many different anatomic and pathological substrates underlie stent thrombosis,5 but here we demonstrate that they are united by the finding of uncovered stent struts.
Finally, with regard to the number of sections studied, we examined serial sections every 2 to 3 mm, eliminating any concerns about selection bias. Just as stent length varies, our sections also vary in number from case to case, depending on the length of the stent. Our data represent the average of the sum of the data collected from each of these sections. We do not agree that our methodology undermines data regarding the location of thrombi and uncovered struts. The location of the thrombus within a stent does not change depending on the sections studied.
Dr Virmani has received research support from Medtronic AVE Guidant, Abbott, W.L. Gore, Atrium Medical Corporation, Boston Scientific, NDC Cordis Corporation, Novartis, Orbus Med-ical Technologies, Biotronik, BioSensors, Alchimer, and Terumo and has served as a consultant to Medtronic AVE Guidant Abbott Laboratories, W.L. Gore, Terumo, and Volcano Therapeutics Inc. The other authors report no conflicts.
Finn AV, Joner M, Nakazawa G, Kolodgie F, Newell J, John MC, Gold HK, Virmani R. Pathological correlates of late drug-eluting stent thrombosis: strut coverage as a marker of endothelialization. Circulation. 2007; 115: 2435–2441.
Iakovou I, Schmidt T, Bonizzoni E, Ge L, Sangiorgi GM, Stankovic G, Airoldi F, Chieffo A, Montorfano M, Carlino M, Michev I, Corvaja N, Briguori C, Gerckens U, Grube E, Colombo A. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA. 2005; 293: 2126–2130.
Pfisterer M, Brunner-La Rocca HP, Buser PT, Rickenbacher P, Hunziker P, Mueller C, Jeger R, Bader F, Osswald S, Kaiser C. Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting versus bare-metal stents. J Am Coll Cardiol. 2006; 48: 2584–2591.
Daemen J, Wenaweser P, Tsuchida K, Abrecht L, Vaina S, Morger C, Kukreja N, Juni P, Sianos G, Hellige G, van Domburg RT, Hess OM, Boersma E, Meier B, Windecker S, Serruys PW. Early and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice: data from a large two-institutional cohort study. Lancet. 2007; 369: 667–678.