Author + information
- Alfredo E. Rodriguez, MD, PhD, FACC, FSCAI⁎ (, )
- Juan Mieres, MD,
- Carlos Fernandez-Pereira, MD,
- Cesar F. Vigo, MD,
- Maximo Rodriguez-Alemparte, MD,
- Daniel Berrocal, MD,
- Liliana Grinfeld, MD, FACC and
- Igor Palacios, MD, FACC, FSCAI
- ↵⁎Otamendi Hospital, Cardiac Unit, Azcuenaga 870, Buenos Aires, 1115, Argentina
To the Editor:
In recent years, the introduction (1) of drug-eluting stents (DES) during percutaneous coronary interventions (PCI) has been one of the major breakthroughs in interventional procedures. Several observational and randomized studies have shown a significantly lower restenosis rate with DES compared with bare-stent technology. Sirolimus-eluting stents (SES) or paclitaxel-eluting stents (PES) stents also substantially reduce the need for repeat revascularization procedures compared with standard stent technology (2–5). However, late safety outcome of these new devices is not well established. Late stent thrombosis, not seen in the first series of studies (1–5), has been recently reported (6,7) and was associated with major adverse cardiac events. Even though a meta-analysis of randomized studies and registries confirmed the efficacy and safety of DES (8), these studies were not powered to detect any increase in late-stent thrombosis. Furthermore, in those studies, stent thrombosis (SET) was not equal and appropriately defined; more importantly, none of the cited studies included SET as a prespecified end point. Therefore, we sought to investigate the incidence of SET in a DES population (9) included prospectively in the multicenter and controlled Argentine Randomized Trial of Coronary Stents versus Bypass Surgery (ERACI III) trial.
From June 2002 to December 2004, 225 patients treated with PCI and DES in five centers in Buenos Aires meeting the clinical and angiographic criteria of the ERACI II trial (10) were prospectively and consecutively included in the ERACI III study. The inclusion criteria of the ERACI studies were previously reported (10). All patients had multiple-vessel disease and were treated with at least one DES, SES, or PES in equal proportion (Cypher, Cordis, Johnson and Johnson, Miami Lakes, Florida; and TAXUS, Boston Scientific Corp., Natick, Massachusetts). The end points of the ERACI III study were to compare major and minor cardiac adverse events at one, two, three, and five years of follow-up between the ERACI III DES patients (n = 225) and ERACI II PCI (n = 225) and ERACI II CABG study patients (n = 225). Comparison of coronary stent thrombosis (SET) between the ERACI III and ERACI II PCI study arm (bare stent) was one of the secondary end points of this study. The purpose of this study was to analyze the incidence of SET during the first 30 days and during follow-up in the ERACI III study patients.
Stent thrombosis was defined as follows:
1. Suspected stent thrombosis (SST), in which the patient experienced unexpected cardiac or sudden death or had a ST-segment elevation myocardial infarction (STEMI) that correlated with the area of DES placement. Patients having non–STEMI myocardial infarctions or whose electrocardiograms at the moment of the acute event could not be reviewed were not included in this category.
2. Confirmed stent thrombosis (CST), in which the patient had angiographically documented stent thrombosis with Thrombolysis In Myocardial Infarction (TIMI) flow grade 0 or 1 or the presence of flow-limiting thrombus (TIMI flow grade 1 or 2). Both SST and CST were counted as definite SET.
Clinical follow-up was made by personal interview or by phone and was obtained in 100% of DES patients during the first 30 days and in 96% of all patients at one year. Patients with an unexpected cardiac or sudden death were included as SST only if the event was certified by a physician present during or immediately after the acute event. Clinical events were adjudicated by a clinical events committee. All PCI procedures were performed according to current guidelines of interventional procedures. Patients were pretreated with loading doses of 300 mg of clopidogrel and aspirin, and dual antiplatelet therapy was maintained for three and six months after the procedure in SES- and PES-eluted stents, respectively.
Baseline clinical and angiographic characteristics of the ERACI III study are described in Table 1.
During the 18.3 ± 8.8 months of follow-up (range 5 to 36 months) from the 225 patients included in the ERACI III study, we identified 7 patients with SET (3.1%). The time course of this phenomenon was between 3 and 927 days after stent deployment. Three patients had SET during the first 30 days after the index procedure, three other patients during the first year afterward, and the last patient 31 months afterward (Table 2).Confirmed stent thrombosis was detected in five patients (2.2%) and SST in the other two (0.9%). Of those patients with SST, one without previous symptoms developed an extensive STEMI (V1to V6) with subsequent death 8 h after symptom onset (Patient #6, SES in left anterior descending and left circumflex, Table 2) and the other had acute pulmonary edema and died 1 h later under cardiac arrest (Patient #7, SES in left main coronary artery, Table 2). Four patients with CST also were treated with bare stent in another vessel, and all of them were patent at the time of the angiography (Table 2). Six of the seven SETs (86%) were related to clopidogrel cessation; Table 2shows the time between discontinuation of clopidogrel and SET. Early (less than three months with SES and six months with PES) discontinuation of dual antiplatelet therapy was required in seven patients, one of whom developed SET, whereas late discontinuation was observed in eight patients, three of whom had SET. Two patients also stopped clopidogrel early, and both developed SET.
Stent thrombosis was always associated with major adverse events: three patients died (43%) and four patients developed an extensive STEMI (57%). Finally, both DES designs had similar incidence of SET (1.9% with SES and 1.5% with PES).
With current antiplatelet therapy, stent thrombosis after coronary bare stent therapy is a rare event after hospital discharge; in fact, in the ERACI II study stent arm, patients were under ticlopidine during one month and after hospital discharge, and no patient had SET during the first year of follow-up (10). Furthermore, in the present study, among patients simultaneously treated with DES and bare stent, CST was present only at the place of DES implantation. The ERACI III study data suggested that SET with DES is unexpected and can occur either early after hospital discharge or very late in the follow-up phase, when many patients have discontinued antiplatelet therapy. The clinical implications of these findings suggest a potential concern with the current widespread use of DES and show the need for larger controlled studies.
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