Late Stent Thrombosis
Abstract & Commentary
By Michael H. Crawford, MD, Professor of Medicine, and Chief of Clinical Cardiology, at the University of California, San Francisco. Dr. Crawford is on the speaker's bureau for Pfizer.
Source: Daemen J, et al. 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.
Despite their advantages in preventing restenosis, drug-eluting stents (DES) have recently been found to be at risk for late stent thrombosis. Because of the popularity of DES there has been considerable interest in this problem. Thus, these investigators from Europe present their long-term experience with sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) used at 2 large academic referral hospitals between 2002-2005. During these 3 years, 8,146 patients underwent percutaneous intervention (PCI) with these 2 stents (3823 SES and 4,323 PES). Patients who received SES had more hypertension, dyslipidemia, diabetes, and smoking. Patients treated with PES were more likely to have acute coronary syndrome and receive more and longer stents. Angiographically proven stent thrombosis occurred in 152 patients for a cumulative incidence of 2.9% over 3 years. Early stent thrombosis (0-30 days) occurred in 60% and late (> 30 days) in 40%. Late stent thrombosis occurred at a constant rate of 0.6% per year. Early stent thrombosis was similar for SES (1.1%) per year and PES (1.3%), but more late stent thrombosis was observed with PES (1.8%) vs SES (1.4%, p = 0.03). Aspirin was recommended indefinitely, but clopidogrel 75 mg/day was advised for at least 6 months with PES and at least 3 months for SES unless the case was complex and then 6 months was recommended for SES. One of the 2 hospitals recommended 12 months of clopidogrel for all stents. At the time of stent thrombosis, dual antiplatelet therapy was being taken by 87% of patients with early thrombosis. Of those with late thrombosis, 51% were on single-drug therapy, 23% on dual therapy, and 26% were on no antiplatelet therapy. Of the patients on aspirin monotherapy who had late stent thrombosis, in 97% thrombosis occurred after clopidogrel therapy was stopped. However, in a multivariate analysis, absence of clopidogrel was not associated with the risk of late thrombosis. Most patients with stent thrombosis presented as myocardial infarction. The authors concluded that late stent thrombosis occurs steadily for up to 3 years after stent implantation in both SES and PES.
Commentary
The intense press coverage of late DES thrombosis prompted the ACC/AHA and other organizations to issue new recommendations for their use. Most practitioners are now adhering more closely to the proven indications for DES, so their use has declined. Also, most are advising their patients to stay on clopidogrel for at least one year based upon anecdotal experience. In this content, this publication of the experience with these stents at 2 large European academic centers is of interest. Although a nonrandomized uncontrolled observational study, it does reflect more of a real world experience because there was unbridled use of DES, and clopidogrel was given largely per the recommendation of the manufacturer at one hospital and for one year at the other. In addition, their patients were sicker and more omplex than the controlled clinical trial patients as evidenced by their 10% overall mortality rate.
The major message of the trial is that late stent thrombosis proceeds at a constant low rate (0.6%/year) despite dual drug therapy in many cases. In fact, clopidogrel use did not emerge as a multivariate predictor of late stent thrombosis. Various theories have been advanced to explain late stent thrombosis such as delayed healing due to the anti-neoplastic agent or a hypersensitivity reaction to the binding polymers, but at this point the mechanism is largely unknown and likely multi-factorial. The differences observed between SES and PES in the incidence of late stent thrombosis may have more to do with clinical factors than the stents themselves. PES was used in more acute coronary syndrome patients and in more long complex lesions.
In addition to the observational nature of the study, angiographic documentation of stent thrombosis was a limitation. Most of the stent thrombosis patients had an acute myocardial infarction. There may have been patients with less severe degrees of restenosis in the population. Also, the data for actual clopidogrel use are incomplete. We know what was advised, but not always what the patient actually did. Thus, firm conclusions about antiplatelet drug use are difficult to support based upon this study.
It is difficult to refute the interventional community's response to this crisis of sticking more closely to evidenced-based indications for DES and a minimum of 12 months of clopidogrel, but there is no solid data to support these actions. Late DES thrombosis seems to be a small, but constant problem after successful stent deployment that we don't know the mechanism of and which we don't know how to prevent. Hopefully, more information will be forthcoming.
Despite their advantages in preventing restenosis, drug-eluting stents (DES) have recently been found to be at risk for late stent thrombosis.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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