November 18, 2008 (New Orleans, Louisiana) — One of the hottest new technologies in the cardiovascular imaging arena is providing a new point of view in the ongoing debate over the safety of drug-eluting stents (DES) for acute MI. A new study using optical coherence tomography (OCT) suggests that exposed and malapposed stent struts in the setting of acute MI (AMI) are indeed more common with DES than with bare-metal stents, but the problem is relatively rare.
But experts not involved in the study are unconvinced, telling heartwire that the technology, while exciting, still has shortcomings that leave many questions unanswered.
The OCT study was conducted in a subset of patients participating in the larger HORIZONS-AMI study, presented at the TCT 2008 meeting, showing a significant reduction in target lesion revascularization at one year in AMI patients treated with DES and no increased risk of adverse events, as compared with bare-metal stents.
Stent struts that do not heal over or that appear to shrink away from the inner surface of the vessel are believed to be an important cause of stent thrombosis, which is an ongoing concern for interventionalists and patients, leading to recommendations for extended dual antiplatelet therapy (12 months or more) post-DES implantation. Researchers have suggested that delayed healing and malapposition may be more common in AMI due to vessel remodeling, the thrombotic milieu, and recent plaque rupture. But until recently, information about stent struts and healing post-DES in patients with AMI has come from autopsy studies, where patients have typically died from stent thrombosis, leading to a clear "selection bias" in terms of understanding the true incidence of the problem.
The OCT analysis from HORIZONS-AMI trial was performed 13 months after stent implantation. According to Dr Giulio Guagliumi (Ospedali Riuniti di Bergamo, Italy), who presented the OCT study results during the American Heart Association 2008 Scientific Sessions, the study is the largest, most detailed imaging study to date to offer a glimpse of how much healing is taking place in DES- vs bare-metal-stent-treated vessels. The results suggest that the rate of strut healing problems for the Taxus paclitaxel-eluting stent is low, less than 5% for exposed stent struts, and just over 1% for strut malapposition. As expected, rates of intimal obstruction were greater for the bare-metal stents than for the Taxus stents.
"What we found is that the vast majority of the struts are covered, so that means that at 13 months, which is an extremely reasonable period of follow-up, about 99% of all the struts from bare-metal stents implanted in AMI were covered. For DES, there was less coverage, but not enormously less--about 94%. Was there a statistically significant difference? Yes, there was, and it was for both uncovered and malapposed struts. And we suspect both may have something to do with the late clinical events, but of course we don't know yet."
A Detailed Snapshot Inside the Vessel
As Guagliumi explained to heartwire , OCT uses infrared light projected within the vessel and acquiring images based on reflected, or "coherent," light. OCT obtains the images by rapidly scanning the interior of the vessel with automatic pullback, providing tomographic images over a 3- to 5-cm length of an artery, gathering slices as thin as 0.1 mm, with a resolution that is 10 to 30 times higher than intravascular ultrasound (IVUS). For their study, Guagliumi and colleagues obtained more than 7000 slices of the 199 stents (155 Taxus; 44 bare-metal Express stents), yielding information on more than 40 000 stent struts. All images were analyzed blindly by an independent core lab.
Guagliumi emphasized that the important thing now will be to track clinical events in relation to OCT observations, something his team is committed to doing over the next four years. In the meantime, he believes OCT will likely play an increasingly important role, not only in research studies assessing vessel healing and other disease settings, but even during stent implantation and subsequent follow-up.
"I think that we had false expectations when we started with DES that it would be nothing to just go in and inflate the balloon and go home; everything is fixed," he said. "Now more and more we are realizing how delicate the balance is between acute implantation success and later events. We are doing a high number of off-label-indication cases, patients and lesions are becoming more and more complex, with more calcification and much less guarantee that in 20 seconds with one balloon, you can have good apposition of the stent and a good job done. And in this case, we need to increase the level of accuracy at the time of implanting and at follow-up: OCT is a new possibility to obtain the best placement. This could be very important in the future."
OCT Opinions
Commenting on the study for heartwire , Dr David Kandzari (Scripps Clinic, La Jolla, CA) pointed out that entrenched concerns about the use of DES in AMI were not necessarily assuaged by the positive results of the overall HORIZONS-AMI study.
"While we are seeing some incremental increase in DES use overall, the rates of DES vs bare-metal stents in AMI remain nearly equal, in large part because of beliefs that target lesion revascularization is lower in AMI patients due to differences in plaque morphology and extent of disease, in addition to outstanding concerns related to delayed endothelialization, impaired healing, and the possibility of acquired stent malapposition," he said.
While the OCT analysis may be reassuring to some operators, the technology has limitations--also noted by Guagliumi and colleagues--chief among them the fact that it cannot actually differentiate between different types of cells or tissue. "Although it has greater resolution that IVUS, OCT can't assume that the absence of neointima means no endothelialization at a cellular level, and similarly, it cannot assume that the presence of tissue on struts is healthy, functional endothelium," Kandzari said. "But, given that the frequency of covered and/or malapposed stent struts in the AMI patients is relatively low--much lower than previously described--the findings are more reassuring than not, but probably not convincing enough to change practice among the bare-metal-stent users."
Other reports of stent malapposition in AMI have suggested the problem may be as high as 32%, Kandzari noted. Indeed, also interviewed by heartwire , Dr Renu Virmani (CV Path Institute, Gaithersburg, MD), pointed to her own autopsy results that suggest the rate of stent malapposition may be closer to 40%.
"After stenting in AMI, stents may not be apposed because thrombus adjacent to stents has since resolved, or they may not be apposed because of abnormal positive remodeling of the vessel away from the stent," Kandzari noted. "I think skeptics would like to know how often abnormal remodeling accounted for these cases of malapposition. And just as we really don't know that neointimal covering alone is the answer against risk of stent thrombosis, we also don't know if having 5% of stent struts 'vulnerable' is 'safe,' or if a patient can come off antiplatelet therapy."
Virmani was even less convinced by the OCT results, suggesting that the 5% figure "underestimated the problem."
"I've never seen a rate as low as 5%," she said. "If it were truly 5%, I would agree it's probably not going to be a problem, clinically, but I think their methodology is probably wrong. . . . They may be seeing fibrin on top of the stent struts, and fibrin is not neointima, it's not healthy. OCT cannot look at the composition of the tissue, and therefore they are reading as 'covered' something that may be covered with a clot."
She also questioned whether the stent malapposition was truly malapposition, since a necrotic core can show up as empty space, implying that the stent struts are not in contact with the vessel wall. "From my experience, having seen cases at autopsy, I do not believe putting DES in AMI patients is the way to go," Virmani told heartwire . "When we looked at stable lesions, we had only 10% to 12% with thrombus. But in a ruptured plaque, there are no cells at the site of rupture; it's necrotic tissue. If you have few or no cells, and you put in a drug that kills whatever cells there are, you are not going to get healing, you're going to make it worse."
Kandzari, however, pointed out that the results are at least somewhat reassuring. "If this [OCT study] showed an unusually high rate of uncovered, malapposed stents, I think it would have 'cast a cloud' on HORIZONS. Fortunately, this wasn't the case."
The complete contents of Heartwire , a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.
Heartwire from Medscape © 2008 Medscape
Cite this: Shelley Wood. AHA 2008: OCT Imaging Suggests Low Rates of Uncovered/Malapposed Struts Following DES for AMI - Medscape - Nov 18, 2008.
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