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The DESIRE-Late Registry

What Is Left to Be Desired?^_*

Department of Cardiology, Bern University Hospital, Bern, Switzerland

Key Words: coronary disease • stents • restenosis

Although the efficacy of first-generation DES remained undisputed, safety concerns soon emerged after the widespread application of these devices in routine clinical practice with a wide range of on-label and off-label indications. Very late stent thrombosis, that is, thrombotic occlusion of the device more than 1 year after implantation, was recognized as a distinct entity complicating the use of first-generation DES with a continuous risk up to 4 years (4). Human autopsy studies and recent clinical investigations of thrombosed DES specimens implied delayed healing, incomplete endothelialization, and vessel remodeling due to chronic inflammation as potential mechanisms leading to this adverse event (5,6). Despite the somewhat increased risk of very late stent thrombosis, comprehensive review of the available evidence showed similar rates of death and myocardial infarction among patients treated with DES and BMS (2). It has been suggested that the slightly increased risk of very late stent thrombosis associated with DES is compensated by adverse events caused by the treatment of the more frequent recurrences with BMS.

It is against this background that the results of the DESIRE (Drug-Eluting Stents in the Real World)-Late registry (7) reported in this issue of JACC: Cardiovascular Interventions must be critically appraised. During a median follow-up time of 5 years of 1,010 patients treated with first-generation DES (sirolimus- and paclitaxel-eluting stents) between 2002 and 2005, the cumulative rate of cardiac death, target vessel revascularization, and major adverse cardiac events amounted to 5.6%, 6.6%, and 15.4%, respectively. The rate of definite and probable stent thrombosis was 1.7%, with more than one-half of events (0.9%) encountered beyond 1 year of stent implantation. The investigators should be applauded for obtaining complete follow-up information in more than 98% of patients. Moreover, there was no protocol-mandated angiographic follow-up, thereby avoiding the oculostenotic reflex and the associated inflation of repeat revascularization procedures.

Although these data are reassuring, event rates in the DESIRE-Late study are low compared with long-term follow-up data derived from meta-analyses and large-scale registries (Table 1) (2,8–11) and require careful scrutiny. First, not all patients undergoing percutaneous coronary intervention at this institution were treated with DES. Instead, BMS were used in more than 50% of patients in 2002 and still in 22% of patients in 2005. It would be of interest to compare event rates among DES and BMS because the selection of patients for a particular stent type may have influenced the favorable results (selection bias). Along the same line, registry studies without monitoring of all patients are susceptible to detection bias because not all events may have been captured, particularly during longer-term follow-up.

Third, the proportion of patients with ST-segment elevation myocardial infarction (12%) at the time of the index procedure as well as the incidence of thrombotic lesions (3%) is lower compared with that in previously published DES registries (4). Acute myocardial infarction has been identified as an independent predictor of very late stent thrombosis, results in an increased incidence of late acquired stent malapposition (13), and has been associated with more extensive inflammation and a higher proportion of uncovered struts compared with stable lesions after DES implantation (14). The lower proportion of patients with acute myocardial infarction in the DESIRE-Late trial therefore may have contributed to the low incidence of very late stent thrombosis.

Fourth, the low overall (1.7%) and very late (0.13% per year) rate of definite and probable stent thrombosis is reminiscent of recent results obtained in the Japanese Cypher registry, with a cumulative incidence of only 0.9% (9). Of note, these results were observed despite a relatively short duration of dual-antiplatelet therapy of 3 to 6 months. Ethnic differences may come into play as they relate to the propensity for the development of hypersensitivity reactions to DES or nonresponsiveness to the thienopyridine clopidogrel and render the results difficult to apply to other patient populations.

How do we apply the results of the DESIRE-Late study to clinical practice? It is certainly reassuring for patients as well as responsible physicians that first-generation DES are associated with an excellent long-term clinical outcome in appropriately selected patients, even in the presence of a short-duration regimen of dual-antiplatelet therapy. Notwithstanding, the results have been obtained with the first generation of sirolimus- and paclitaxel-eluting stents, which have been superseded by the advent of newer-generation DES. Excellent short- and long-term clinical outcome have been reported with newer-generation DES, as summarized in Table 2 (15–20). Although it is still premature to definitively conclude, available data suggest that newer-generation DES may put to rest previous concerns of very late stent thrombosis.

	Footnotes

 
Dr. Windecker is a consultant for and receives lecture fees from Abbott, Biosensors, Biotronik, Boston Scientific, Medtronic, and Johnson & Johnson.

^_* Editorials published in JACC: Cardiovascular Interventions reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Interventions or the American College of Cardiology.

^_* Reprint requests and correspondence: Dr. Stephan Windecker, Department of Cardiology, Bern University Hospital, Freiburgstrasse, 3010 Bern, Switzerland (Email: stephan.windecker{at}insel.ch).

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