Late Coronary Stent Thrombosis
Late Coronary Stent Thrombosis
Abstract & Commentary
Wang and colleagues sought to determine the frequency and timing of stent thrombosis in patients who underwent stent implantation (without brachytherapy) at their institution between January 1996 and November 1999. The patients were identified retrospectively as part of a quality improvement program in invasive cardiology where adverse events were adjudicated by committee. Stent thrombosis was defined as total vessel occlusion with evidence of myocardial infarction (MI) including sudden onset of symptoms, electrocardiographic changes of acute MI in the vascular distribution of the stented artery, and elevated biochemical markers. The timing of stent thrombosis was defined as early (within 30 days of implantation) or late (greater than 30 days after implantation). Patients who met criteria for stent thrombosis were matched with control patients (the next patients chronologically to undergo stent implantation) using a 1:3 ratio.
In this trial, 1191 patients underwent successful stent implantation during the study period. Of these, 20 (1.68%) met diagnostic criteria for stent thrombosis. Eleven (0.92%) were early and 9 (0.76%) were late thrombotic events. Of the early stent thromboses, only 2 occurred within the first 24 hours after the procedure. Timing of late stent thrombosis ranged from 39-211 days (mean, 109) post-procedure. Only 3 of the late stent thrombosis patients reported recurrent angina prior to their late thrombosis event, while the remaining 6 patients had no warning symptomatology. There were no differences in baseline clinical or angiographic variables between the thrombosis and control groups, or between the patients with early and late stent thrombosis. There were no differences between the stent thrombosis and control groups with respect to procedural variables including stent length, inflation pressure, final balloon diameter, final minimal lumen diameter (MLD), residual stenosis or duration of procedure. However, stented length was longer (36 ± 20 vs 21 ± 12, P = 0.02) and final MLD was smaller (2.8 ± 0.04 vs 3.2 ± 0.05, P = 0.04) in the patients with early compared to late stent thrombosis. All patients received aspirin and a thienopyridine derivative post-procedure. There were no differences in rates of stent thrombosis between patients receiving ticlopidine vs. those receiving clopidogrel, or between those receiving a 4-week vs. 2-week long regimen of thienopyridine therapy post-procedure. Of the 20 patients with stent thrombosis, 1 died before PCI could be performed, 18 underwent successful repeat PC, and 1 underwent coronary bypass surgery after unsuccessful attempted PCI.
Wang et al conclude that, while infrequent, late stent thrombosis, beyond 30 days after stent implantation constitutes a larger proportion than perhaps previously recognized, accounting for almost half of the cases of stent thrombosis identified at their institution. Wang et al acknowledge that their method of identifying patients with stent thrombosis might even underestimate the frequency of this complication. They did not identify clinical or angiographic characteristics that could be used to identify which patients are at risk of late stent thrombosis. They conclude that a randomized trial will be necessary to determine whether longer-term antiplatelet therapy might reduce the risk of late stent thrombosis (Wang F, et al. Catheter Cardiovasc Interv. 2002;55:142-147).
Comment by Sarah M. Vernon, MD
In recent years, the percentage of PCI procedures culminating in stent implantation has approached 80-90% in many interventional laboratories in the United States. Despite improved procedural technique and adjuvant medical therapies, 2 post-procedural complications unique to stented vessels persist, namely in-stent restenosis and stent thrombosis, which had been thought to occur most commonly in the acute (< 24-48 hours post-procedure) or the subacute (48 hours to 30 days post-procedure) phase. Restenosis complicates on the order of 10-25% of stent implantation procedures, and while it is clearly the more common adverse outcome, it is rarely life threatening. In contrast, stent thrombosis, while uncommon, remains a serious source of concern because of its lack of warning symptomatology and its potentially severe consequences, most notably ST-elevation MI or even sudden death. Improved stent design, lesion and stent selection, implantation techniques (particularly high-pressure balloon inflation and IVUS guidance), and optimal antiplatelet therapies both during, but more importantly, after coronary interventional procedures have reduced, but not eliminated, the specter of this dreaded complication. The risk of subacute stent thrombosis has been felt to be highest in the first 30 days after implantation, prior to endothelialization of the newly implanted foreign body or reendothelialization of local injury created by the implantation procedure. When contemporary pharmacologic therapy with clopidogrel and aspirin for 4 weeks is used, stent thrombosis within the first 30 days after implantation complicates less than 2% of stent implantation procedures. Recently, concern regarding the late thrombotic events occurring in stented patients treated has arisen from trials of patients treated with intracoronary brachytherapy has begun to reshape this conventional wisdom. In these cases, the substrate for late stent thrombosis is thought to be inadequate or delayed endothelialization. Hence, more prolonged antiplatelet therapy (6-12 months of clopidogrel) has been recommended in stented patients receiving brachytherapy. The present report from Wang et al would suggest that this phenomenon may not be limited to patients treated with brachytherapy and that the incidence of late stent thrombosis in conventionally treated stent patients might be higher than previously recognized. As Lasala points out in the accompanying editorial, little is known about the true incidence of stent thrombosis beyond the first 30 days, in part because of the low frequency of such events, but also because most clinical trials designed to address stent thrombosis to date have been limited to 30-day end points.1 The data from Wang et al would suggest that late stent thrombosis may be more common than we know. Perhaps we are not "out of the woods" when the patient takes his last tablet of clopidogrel at 30 days. The potential use of long-term antiplatelet therapy with clopidogrel in reducing adverse events in other populations of patients with coronary artery disease was also demonstrated in the CURE and PCI-CURE trials published last fall.2,3 This recent report suggests that long-term (or at least longer) antiplatelet therapy may eventually prove to be warranted in all patients receiving coronary stents.
References
1. Lasala JM. Catheter Cardiovasc Interv. 2002;55: 150-151.
2. The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. N Engl J Med. 2001; 345:494-502.
3. Mehta SR, et al. Lancet. 2001;358:527-533.
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