Volumetric Intravascular Ultrasound Analysis of Paclitaxel-Eluting and Bare Metal Stents in Acute Myocardial Infarction
The Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction Intravascular Ultrasound Substudy
Background— Vascular responses to drug-eluting stents in ST-segment elevation myocardial infarction are unknown. In the prospective, multicenter Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, patients with ST-segment elevation myocardial infarction within 12 hours of symptom onset were randomized 3:1 to TAXUS EXPRESS paclitaxel-eluting stents (PES) or EXPRESS bare metal stents (BMS).
Methods and Results— A formal intravascular ultrasound substudy enrolled 464 patients with baseline and 13-month follow-up imaging at 36 centers. Overall, 446 lesions in 402 patients were suitable for standard qualitative and quantitative analyses, which were performed at an independent blinded core laboratory. The primary prespecified end point was the in-stent percent net volume obstruction at follow-up. Median stent length measured 23.4 mm (first and third quartiles, 18.5 and 31.9 mm). PES compared with BMS significantly reduced 13-month percent net volume obstruction (6.5% [first and third quartiles, 2.2% and 10.8%] versus 15.6% [first and third quartiles, 7.2% and 28.8%]; P<0.0001). PES compared with BMS also resulted in more late-acquired stent malapposition (29.6% versus 7.9%; P=0.0005) resulting from positive vessel remodeling. Plaque and/or thrombus protrusion through stent struts was initially present in 70.4% of PES and 64.8% of BMS; all resolved during follow-up. New aneurysm formation, stent fracture, and subclinical thrombus were uncommon, although seen only in PES.
Conclusions— PES compared with BMS significantly reduce neointimal hyperplasia in patients with ST-segment elevation myocardial infarction but also result in a high frequency of late-acquired stent malapposition as a result of positive vessel remodeling. Ongoing long-term follow-up is required to establish the clinical significance of these findings.
Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00433966.
Received April 17, 2009; accepted September 1, 2009.
Compared with balloon angioplasty alone, bare metal stents (BMS) reduce recurrent ischemia and repeat revascularization in patients with ST-segment elevation myocardial infarction (STEMI).1,2 Drug-eluting stents (DES) further reduce restenosis compared with BMS, especially in complex patient and lesion cohorts such as diabetes, long lesions, and small vessels.3–5 Recent studies have demonstrated similar benefits of DES in patients undergoing primary percutaneous coronary intervention (PCI).6–8 Intravascular ultrasound (IVUS) provides unique insights into stent implantation, although the vascular responses to DES in patients with acute myocardial infarction undergoing primary PCI have been incompletely characterized.9 In the large-scale, prospective, multicenter Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, a formal IVUS substudy was performed, the results of which are reported here.
Clinical Perspective on p 1882
HORIZONS-AMI was a prospective, open-label, multicenter, dual-arm 2×2 factorial randomized trial in patients with STEMI presenting <12 hours after symptom onset and undergoing primary PCI.10 The 2 randomization arms consisted of the direct thrombin inhibitor bivalirudin alone versus heparin plus a glycoprotein IIb/IIIa inhibitor (1:1 randomization) and TAXUS EXPRESS paclitaxel-eluting stents (PES) versus otherwise equivalent EXPRESS BMS (3:1 randomization). Among patients undergoing stent randomization, 13-month angiographic follow-up was prespecified for 1800 patients in whom the stent implantation procedure was successful (diameter stenosis <10% with Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow with National Heart, Lung, and Blood Institute type A or less peri-stent dissection), in whom only study stents were implanted, and in whom neither stent thrombosis occurred nor bypass surgery was performed within 30 days. Among this cohort, a formal IVUS substudy was completed. IVUS sites were preselected on the basis of the their desire to participate in this substudy and their agreement to perform baseline (poststent) and follow-up IVUS on consecutive patients in the angiographic follow-up cohort until at least up 300 consecutive IVUS cases were completed.
The details of the first randomization (pharmacology arm) have been previously reported.10 After the first randomization and coronary angiography, eligibility for the second randomization (stent arm) was assessed. If TIMI grade 0/1 flow was present at baseline, the artery was predilated, and TIMI grade 2/3 flow was restored. Stent randomization angiographic inclusion criteria required the presence of ≥1 infarct artery (estimated reference diameter, 2.25 to 4.0 mm) in which all significant lesions could be treated with study stents. The principal exclusion criteria included bifurcation lesions requiring planned implantation of 2 stents, need for >100 mm of study stent length, infarct-related artery in an unprotected left main segment, significant multivessel disease or anatomic features indicating a high likelihood of bypass surgery within 30 days, unidentifiable culprit vessel or lesion, and the presence of a previous culprit lesion stent.
Quantitative and Qualitative Coronary Angiography
Coronary angiograms at baseline, immediately after PCI, and at follow-up were performed in at least 2 orthogonal views after intracoronary nitroglycerin. Angiograms were analyzed at the Angiographic Core Laboratory of the Cardiovascular Research Foundation (New York, NY) with the CMS-GFT algorithm (MEDIS, Leiden, the Netherlands). Minimum lumen diameter (MLD) and mean reference diameter (RD), obtained by averaging 5-mm segments proximal and distal to the target lesion location, were used to calculate diameter stenosis as follows: (1−MLD/RD)×100. Late loss was the change in MLD from final PCI to follow-up. In-stent analysis was confined to the stent itself, and in-segment analysis included the stent plus 5-mm segments proximal and distal to the stent. Binary restenosis was defined as a ≥50% diameter stenosis. Qualitative analysis was done with standard published methods.11
IVUS Imaging and Analysis
Allowable IVUS systems included iLab, Galaxy, and ClearView (all with Atlantis SR Pro, 40-MHz catheters; Boston Scientific, Fremont, Calif) or In Vision Gold with 20-MHz EagleEye catheters (Vocano Therapeutics, Rancho Cordova, Calif). IVUS imaging was performed with motorized pullback at 0.5 mm/s to include the stent and >5 mm segments proximal and distal to the stent. IVUS studies were archived onto super-VHS tape, CD-ROM, or DVD and sent to an independent, treatment-allocation–blinded, IVUS core laboratory (Cardiovascular Research Foundation) for quantitative and qualitative analyses with validated planimetry software (EchoPlaque, INDEC Systems, Inc, Mountain View, Calif).
Quantitative analysis included measurement every 1 mm of the external elastic membrane (EEM), stent, and lumen cross-sectional areas (CSAs). Plaque plus media CSA was calculated as EEM minus lumen. Neointimal hyperplasia (NIH) was calculated as stent minus lumen.12 Once a complete set of CSA measurements was obtained, intrastent and stent-edge volumes (EEM, plaque plus media, stent, lumen, and NIH) were calculated with Simpson’s rule and normalized for stent and reference segment length. Percent net volume obstruction was calculated as NIH divided by stent volume. Volumetric analysis was performed only for lesions in which motorized pullback was consistent and reliable, and planar analysis at minimum lumen area (MLA) and reference site was performed for all lesions except 8 (4 lesions at baseline and 4 lesions at follow-up in which ≥80% of the entire segment was imaged but MLA site was highly suspected as not imaged such as distal stent edge); these 8 lesions were used only for qualitative analysis.
Qualitative analysis included stent malapposition (blood speckle behind stent struts), categorized as persistent (visible both at baseline and follow-up), resolved (visible only at baseline), and late acquired (only visible at follow-up); intrastent plaque and/or thrombus protrusion (IVUS cannot reliably differentiate between plaque and thrombus protruding through stent struts); stent fracture (absence of struts over more than one third of the stent circumference); aneurysm (lumen >50% larger than the proximal reference); and edge dissection.
The primary, prespecified IVUS end point was in-stent percent net volume obstruction in all patients with analyzable studies at follow-up. Assuming a percent net volume obstruction in the control arm of 29±15%, allowing for 20% attrition, and including 240 analyzable patients with 13-month IVUS follow-up (60 in the BMS control arm and 180 in the PES arm), the study had 80% power to detect a 6.3% absolute difference in percent net volume obstruction (ie, mean of 22.7±15%), representing a relative 22% reduction with PES. Categorical variables were compared with χ2 statistics or the Fisher exact test. Continuous variables were compared with the Wilcoxon rank-sum test and displayed as median and first and third quartiles. Baseline patient clinical characteristics were analyzed on the patient level, and angiographic and IVUS characteristics were analyzed on a per-lesion level.
Between March 25, 2005, and May 7, 2007, a formal IVUS substudy enrolled 464 patients with baseline and 13-month follow-up imaging at 36 centers. IVUS was completed in 406 patients and sent to the core laboratory for analysis. From these cases, 389 (95.8%, including 294 PES and 95 BMS) contained 429 lesions that were analyzable (4.2% were excluded because of poor image quality [n=7], no final IVUS image [n=7], or other reasons [n=3]). Overall, 425 of 429 lesions (99.1%) were suitable for planar analysis, and 381 of 429 lesions (88.8%) were suitable for volumetric analysis. IVUS follow-up was completed and sent to the core laboratory for analysis in 268 patients (66.0%). From these cases, 258 (96.3%, including 196 PES and 62 BMS) contained 286 lesions that were analyzable, 256 of which (89.5%) were suitable for volumetric analysis. A total of 13 patients had analyzable follow-up IVUS but not baseline IVUS. Thus, both paired baseline IVUS and follow-up IVUS from 245 patients with 262 lesions were received in the core laboratory, including IVUS on 204 patients (218 lesions) with analyzable volumetric images as well as an additional 41 patients (44 lesions) with only analyzable planar images.
Clinical and angiographic features were well matched between groups (Tables 1 through 3⇓⇓). Median age was 60.5 years, and 78.9% were men. Preintervention angiographic thrombus was present in 71.4% of lesions. Postprocedure angiographic MLD was similar for PES and BMS. However, at 13 months, angiographic late lumen loss, diameter stenosis, and binary restenosis rates were significantly less with PES than BMS (Table 3).
Planar Quantitative IVUS Analysis
Postprocedural MLA was similar in PES and BMS and slightly smaller than the minimum stent area because of the presence of plaque and/or thrombus protrusion through stent struts in 69% of lesions (Table 4). Median stent expansion (minimum stent area compared with the average of proximal and distal reference lumen CSAs) was similar with PES (0.73; first and third quartiles, 0.63 and 0.85) and BMS (0.75; first and third quartiles, 0.67 and 0.87). MLA at follow-up was significantly larger in PES than BMS (5.8 mm2 [first and third quartiles, 4.3 and 7.6 mm2] versus 5.2 mm2 [first and third quartiles, 3.5 and 6.7 mm2]; P=0.03) because of less NIH.
Volumetric Quantitative IVUS Analysis
At baseline, the measured length of PES was slightly greater than BMS; the 2 groups were otherwise well matched (Table 5). At the 13-month follow-up, percent net volume obstruction was significantly less with PES than BMS (median, 6.5% [first and third quartiles, 2.2% and 10.8%] versus 15.6% [first and third quartiles, 7.2% and 28.8%]; mean, 7.9±7.4% versus 19.8±15.8%; both P<0.0001), resulting in larger luminal volume. There was an increase from baseline to follow-up in mean EEM CSA within the stented segment in PES (positive remodeling) but not in BMS. There were no differences in serial measures of the proximal reference segment dimensions adjacent to PES and BMS. However, in the distal reference segment, there was a decrease in mean EEM CSA with BMS (negative remodeling) but no change in mean EEM CSA adjacent to PES.
Qualitative IVUS Analysis
Postprocedural stent–vessel wall malapposition was present at a similar rate in both groups (Table 6). During follow-up, the increase in mean EEM CSA after PES implantation (but not after BMS) resulted in more late-acquired stent–vessel wall malapposition with PES compared with BMS (29.6% versus 7.9%; P=0.0005; the Figure). As a result of the greater incidence of late-acquired malapposition, the overall rate of malapposition (persistent or acquired) at follow-up was 45.2% with PES compared with 23.9% with BMS (P=0.002). However, maximum stent malapposition CSAs at baseline and follow-up were relatively small (median CSA, ≈1.5 mm2 at both time periods with both stents; Table 6).
At follow-up, all occurrences of luminal plaque and/or thrombus protrusion noted at baseline immediately after stent implantation had resolved; new intrastent thrombus was present in 1 PES patient. Stent-edge dissections were infrequent at baseline; approximately two thirds of proximal dissections and all but 1 distal dissection had healed during follow-up. Two coronary aneurysms developed during follow-up in PES-treated lesions compared with none in BMS-treated lesions. There were no baseline stent fractures in either group. At follow-up, fractures were identified in 6 PES (2.7%; all of which were also angiographically visible). Restenosis developed in 2 of the patients with stent fractures, although at locations remote from the fracture site, and neither resulted in lumen compromise at the fracture site, aneurysm formation, or thrombosis. There were no late BMS fractures.
The main findings of the IVUS substudy from the HORIZONS-AMI trial, representing the largest such experience to date with DES in STEMI, are the following: (1) PES compared with BMS significantly reduced 13-month percent net volume obstruction and NIH; (2) PES had a higher incidence of late-acquired stent malapposition than BMS because of positive vessel remodeling; (3) plaque and/or thrombus protrusion through the stents struts immediately after stent implantation was present in approximately two thirds of cases (both PES and BMS), all of which resolved during follow-up; and (4) new aneurysm formation, stent fractures, and subclinical thrombus were uncommon, although seen only with PES.
Previous STEMI trials have reported lower rates of target lesion revascularization with DES compared with BMS.13 In HORIZONS-AMI, randomization to PES versus BMS reduced the 12-month rate of target lesion revascularization from 7.5% to 4.5% (P=0.002).14 The reduction in percent volume obstruction as a result of less NIH with PES compared with BMS as demonstrated by IVUS in the present study underlies this clinical benefit. In the recent AMI trial, serial IVUS evaluation in 208 patients showed significant NIH reduction with Cypher sirolimus-eluting stents (SES) compared with BMS (mean, 3.3±5.0% versus 27.0±11.0%; P<0.001).9 The percent net volume obstruction for PES-treated lesions in the present study (median, 6.5%; mean, 7.9±7.4%) is slightly more than with SES in AMI but less than previously reported with PES from a pooled analysis of IVUS data from 292 non-STEMI lesions in the TAXUS IV, V, and VI trials (mean, 12.4±11.8%).15 Autopsy studies of DES implanted into culprit lesions of STEMI patients have demonstrated more exposed stent struts and less NIH compared with target lesions in stable angina patients.16 The present study supports the hypothesis that DES implantation in lesions responsible for STEMI results in a less vigorous healing response than in more stable plaques. Although no difference in stent thrombosis was present between PES and BMS at 1 year in the 3006 patients randomized in the HORIZONS-AMI trial,14 ongoing follow-up will determine whether a very late stent thrombosis risk is present after PES implantation in STEMI.
Previous IVUS studies have documented late-acquired stent malapposition in ≈5% of BMS in non-STEMI patients, ≈5% to 15% of BMS in STEMI patients and DES in non-STEMI patients, and ≈25% to 30% of DES in STEMI patients.9,15,17–20 Late-acquired stent malapposition in STEMI has been reported in 25% of SES compared with 5% of BMS patients, with an incidence of any malapposition at follow-up (persistent or acquired) of 37.5% for SES compared with 12.5% for BMS.9 The current analysis is consistent with these previous reports. Late-acquired stent malapposition is more common with all stent types after implantation in STEMI compared with stable angina lesions, but especially with DES.
Late-acquired stent malapposition is typically the result of positive vessel wall remodeling.17–20 Significant positive vessel remodeling during follow-up in the present study was present with PES but not BMS, contributing to the higher rate of late-acquired stent malapposition with PES. Thrombus resolution behind the stent struts may also contribute to late-acquired stent malapposition in STEMI after both BMS and DES.
A clinical association between persistent or late-acquired stent malapposition and subsequent thrombosis remains controversial. Cook et al21 reported that 10 of 13 patients with very late stent thrombosis (mean, 1.7 years after stent implantation) had stent malapposition, with a malapposition area twice as large as in patients with malapposition without very late stent thrombosis (mean, 8.3 versus 4.0 mm2). The maximum malapposition area in the present study was relatively small with both stents (median, 1.5 mm2; mean±SD, 2.3±2.5 mm2); this may explain the lack of events in the present patient cohort with late stent malapposition. Longer-term follow-up is necessary to determine whether the frequent occurrence of late-acquired malapposition after stenting in STEMI (especially with DES) is of clinical concern.
In the present study, postprocedural plaque and/or thrombus protrusion through stent struts was detected in approximately two thirds of STEMI patients whether treated with PES or BMS. A previous IVUS study reported tissue protrusion in 27% of 310 acute infarct-related lesions, but only 40% had STEMI <24 hours from symptom onset.22 Other studies in non-STEMI patients have reported a 17% to 23% incidence of tissue protrusion and an association between tissue protrusion and postprocedural creatine kinase-MB elevation but not subsequent NIH.23,24 In the present study, the high rate of plaque and/or thrombus protrusion with resolution during follow-up in all cases suggests that intraluminal thrombus was present in most. Nevertheless, because IVUS cannot reliably differentiate plaque and mural thrombus from neointima, we cannot exclude the possible contribution of persistent atheroma or thrombus protrusion to subsequent NIH.25
Stent fracture is increasingly being recognized as a cause of DES failure, especially with SES.26,27 In a prior retrospective IVUS study of 17 non-STEMI patients with 20 stent strut fractures, 18 (90%) occurred in SES, 2 (10%) in BMS, but none in PES.26 Of note, 5 of 20 stent fractures were accompanied by coronary aneurysm formation, and 2 were associated with very late stent thrombosis. Angiographic data from 3 prior PES trials in nonacute coronary syndromes revealed a 1.1% rate of stent fracture after PES implantation associated with restenosis and/or stent thrombosis.27 The frequency and implications of stent fracture have not previously been reported in STEMI. In the present study, there were 6 EXPRESS PES fractures (2.7%) but no EXPRESS BMS fractures (a nonsignificant difference likely resulting from chance because the underlying stent architectures are identical), and none directly resulted in restenosis, thrombosis, and/or aneurysm formation. Additional studies are required to determine whether stent fractures are more common in the STEMI setting (with PES or other stent types) and to define the rate and pattern of clinical consequences.
The present study demonstrated a comparable frequency of both postprocedural edge dissections and subsequent healing during follow-up with PES and BMS. The Diabetes and Sirolimus-Eluting Stent (DIABETES) study also reported similar rates of resolved and persistent edge dissections with SES and BMS in non-STEMI patients.28 In an examination of the vascular responses of the 5-mm proximal and distal reference margins in the present study, the only notable finding was that the reference mean EEM CSA did not decrease distal to PES stents in contrast to BMS.
Several limitations of the present study should be noted. Despite the fact that the HORIZONS-AMI is the largest IVUS multicenter trial completed to date, potential selection bias cannot be excluded. Follow-up IVUS may not be performed in lesions with severe restenosis or in small vessels. Conversely, some investigators may avoid invasive imaging in an asymptomatic patient with a widely patent vessel. Moreover, patients in the IVUS substudy were highly selected; sites had to agree to participate, and only patients in whom study stents were implanted, in whom the procedure was successful and uncomplicated, and in whom no stent thrombosis occurred or coronary artery bypass graft surgery was performed within 30 days were enrolled. Thus, by design, there are major differences between patients included and those not included in the IVUS substudy. Nonetheless, the magnitude of reduction in NIH and the rate of increased late-acquired malapposition with PES compared with BMS were marked and thus likely to represent real findings. Finally, because angiographic and IVUS characteristics were calculated by a per-lesion analysis and clinical characteristics were calculated by a per-patient analysis, some of the tested variables may be correlated.
PES significantly reduced NIH and percent net volume obstruction compared with BMS in patients with STEMI, resulting in lower rates of recurrent ischemia and repeat target lesion revascularization, but PES also more frequently resulted in positive vessel remodeling and late-acquired stent malapposition. Aneurysm formation, stent fracture, and development of subclinical thrombus, although rare, may also be more common with PES than BMS. Ongoing long-term follow-up is required to establish the clinical significance of these findings.
Sources of Funding
This work was sponsored by the Cardiovascular Research Foundation, with grant support from Boston Scientific and The Medicines Co.
Drs Maehara, Lansky, and Parise report being employed by the Cardiovascular Research Foundation. Dr Maehara reports receiving research grants from Boston Scientific and Volcano. Dr Mintz reports receiving consulting fees from Boston Scientific, Volcano, and Abbott Vascular. Dr Witzenbichler reports receiving lecture fees from Boston Scientific, Abbott Vascular, and The Medicines Co. Dr Guagliumi reports receiving consulting fees from or serving on advisory boards for Abbott Vascular and Boston Scientific and receiving grant support from Medtronic and Boston Scientific. Dr Mehran reports receiving lecture fees from Boston Scientific and The Medicines Co. Dr Stone reports receiving grant support from Boston Scientific, The Medicines Co, and Abbott Vascular and consulting fees from Volcano. The other authors report no conflicts.
Stone GW, Ellis SG, Cannon L, Mann JT, Greenberg JD, Spriggs D, O'Shaughnessy DeMaio S, Hall P, Popma JJ, Koglin J, Russell ME. Comparison of a polymer-based paclitaxel-eluting stent with a bare metal stent in patients with complex coronary artery disease. JAMA. 2005; 294: 1215–1223.
Moses JW, Leon MB, Popma JJ, Fitzgerald PJ, Holmes DR, O'Shaughnessy C, Caputo RP, Kereiakes DJ, Williams DO, Teirstein PS, Jaeger JL, Kuntz RE. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med. 2003; 349: 1315–1323.
Fajadet J, Wijns W, Laarman GJ, Kuck KH, Ormiston J, Münzel T, Popma JJ, Fitzgerald PJ, Bonan R, Kuntz RE. Randomized, double-blind, multicenter study of the endeavor zotarolimus-eluting phosphorylcholine-encapsulated stent for treatment of native coronary artery lesions. Circulation. 2006; 114: 798–806.
van der Hoeven BL, Liem SS, Jukema JW, Suraphakdee N, Putter H, Dijkstra J, Atsma DE, Bootsma M, Zeppenfeld K, Oemrawsingh PV, van der Wall EE, Schalij MJ. Sirolimus-eluting stents versus bare-metal stents in patients with ST-segment elevation myocardial infarction: 9-month angiographic and intravascular ultrasound results and 12-months clinical outcome. J Am Coll Cardiol. 2008; 51: 618–626.
Popma JJ, Almonacid A, Lansky AJ. Qualitative and quantitative coronary angiography. In: Topol EJ, ed. Textbook of Interventional Cardiology. Philadelphia, Pa: Saunders; 2008: 1071–1093.
Mintz GS, Nissen SE, Anderson WD, Rosenfield K, Bailey SR, Siegel RJ, Erbel R, Tuzcu EM, Fitzgerald PJ, Yock PG, Pinto FJ. American College of Cardiology clinical expert consensus document on standards for acquisition, measurement and reporting of intravascular ultrasound studies (IVUS): a report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2001; 37: 1478–1492.
De Luca G, Stone GW, Suryapranata H, Laarman GJ, Menichelli M, Kaiser C, Valgimigli M, Di Lorenzo E, Dirksen MT, Spaulding C, Pittl U, Violini R, Percoco G, Marino P. Efficacy and safety of drug-eluting stents in ST-segment elevation myocardial infarction: a meta-analysis of randomized trials. Int J Cardiol. 2009; 133: 213–222.
Stone GW, Lansky AJ, Pocock SJ, Gersh BJ, Dangas G, Wong SC, Witzenbichler B, Guagliumi G, Peruga JZ, Brodie BR, Dudek D, Möckel M, Ochala A, Kellock A, Parise H, Mehran R. Paclitaxel-eluting stents versus bare-metal stents in acute myocardial infarction. N Engl J Med. 2009; 360: 1946–1959.
Weissman NJ, Ellis SG, Grube E, Dawkins KD, Greenberg JD, Mann T, Cannon LA, Cambier PA, Fernandez S, Mintz GS, Mandinov L, Koglin J, Stone GW. Effect of the polymer-based, paclitaxel-eluting TAXUS Express stent on vascular tissue response: a volumetric intravascular ultrasound integrated analysis from the TAXUS IV, V, and VI trials. Eur Heart J. 2007; 28: 1574–1582.
Nakazawa G, Finn AV, Joner M, Ladich E, Kutys R, Mont EK, Gold HK, Burke AP, Kolodgie FD, Virmani R. Delayed arterial healing and increased late stent thrombosis at culprit sites after drug-eluting stent placement for acute myocardial infarction patients. Circulation. 2008; 118: 1138–1145.
Shah VM, Mintz GS, Apple S, Weissman NJ. Background incidence of late malapposition after bare-metal stent implantation. Circulation. 2002; 106: 1753–1755.
Hong MK, Mintz GS, Lee CW, Kim YH, Lee SW, Song JM, Han KH, Kang DH, Song JK, Kim JJ, Park SW, Park SJ. Incidence, mechanism, predictors, and long-term prognosis of late stent malapposition after bare-metal stent implantation. Circulation. 2004; 109: 881–886.
Hong MK, Mintz GS, Lee CW, Park DW, Park KM, Lee BK, Kim YH, Song JM, Han KH, Kang DH, Cheong SS, Song JK, Kim JJ, Park SW, Park SJ. Late stent malapposition after drug-eluting stent implantation: an intravascular ultrasound analysis with long-term follow-up. Circulation. 2006; 113: 414–419.
Cook S, Wenaweser P. Togni M, Billinger M, Morger C, Seiler C, Vogel R, Hess O, Meier B, Windecker S. Incomplete stent apposition and very late stent thrombosis after drug-eluting stent implantation. Circulation. 2007; 115: 2426–2434.
Futamatsu H, Sabeté M, Angiolillo DJ, Quevedo PJ, Corros C, Futamatsu KM, Alfonso F, Jiang J, Cervinka P, Antolin RH, Macaya C, Bass TA, Costa MA. Characterization of plaque prolapse after drug-eluting stent implantation in diabetic patients: a three dimensional volumetric intravascular ultrasound outcome study. J Am Coll Cardiol. 2006; 48: 1139–1145.
Doi H, Maehara A, Mintz GS, Tsujita K, Kubo T, Castellanos C, Liu J, Yang J, Oviedo C, Aoki J, Franklin-Bond T, Dasgupta N, Lansky AJ, Dangas GD, Stone GW, Moses JW, Mehran R, Leon MB. Classification and potential mechanisms of intravascular ultrasound patterns of stent fracture. Am J Cardiol. 2009; 103: 818–823.
Popma JJ. Strut fractures after DES: definitions, frequency, timing, device specificity, and associated clinical events. Transcatheter Cardiovascular Therapeutics. http://www.tctmd.com/txshow.aspx?tid=2532&id=73192&trid=2380. Accessed April 8, 2009.
Quevedo PJ, Sabaté M, Angiolillo DJ, Costa MA, Alfonso F, Hospital JAG, Antolín RH, Bañuelos C, Goicolea J, Avilés FF, Bass T, Escaned J, Moreno R, Fernández C, Macaya C. Vascular effects of sirolimus-eluting versus bare-metal stents in diabetic patients: three-dimensional ultrasound results of the diabetes and sirolimus-eluting stent (DIABETES) trial. J Am Coll Cardiol. 2006; 47: 2172–2179.
In the prospective, multicenter Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, patients with ST-segment elevation myocardial infarction within 12 hours of symptom onset were randomized 3:1 to TAXUS EXPRESS paclitaxel-eluting stents or EXPRESS bare metal stents. The intravascular ultrasound substudy enrolled 464 patients with baseline and 13-month follow-up imaging at 36 centers. Paclitaxel-eluting compared with bare metal stents significantly reduced percent net volume obstruction (6.5% [first and third quartiles, 2.2% and 10.8%] versus 15.6% [first and third quartiles, 7.2% and 28.8]; P<0.0001) but also resulted in more late-acquired stent malapposition (29.6% versus 7.9%; P=0.0005) resulting from positive vessel remodeling. Plaque and/or thrombus protrusion through stent struts was initially present in 70.4% of paclitaxel-eluting stents and 64.8% of bare metal stents; all resolved during follow-up. New aneurysm formation, stent fracture, and subclinical thrombus were uncommon, although seen only in paclitaxel-eluting stents. The present data demonstrate a reduction in neointimal hyperplasia and restenosis in ST-segment elevation myocardial infarction patients treated with paclitaxel-eluting stents compared with bare metal stents. Long-term follow-up is required to establish whether the increased frequency of late-acquired stent malapposition with paclitaxel-eluting stents has clinical significance.