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Brief Report |

Incidence, Predictors, and Outcome of Thrombosis After Successful Implantation of Drug-Eluting Stents FREE

Ioannis Iakovou, MD; Thomas Schmidt, MD; Erminio Bonizzoni, PhD; Lei Ge, MD; Giuseppe M. Sangiorgi, MD; Goran Stankovic, MD; Flavio Airoldi, MD; Alaide Chieffo, MD; Matteo Montorfano, MD; Mauro Carlino, MD; Iassen Michev, MD; Nicola Corvaja, MD; Carlo Briguori, MD; Ulrich Gerckens, MD; Eberhard Grube, MD; Antonio Colombo, MD
[+] Author Affiliations

Author Affiliations: Centro Cuore Columbus and San Raffaele Hospital, Milan, Italy (Drs Iakovou, Ge, Sangiorgi, Stankovic, Airoldi, Chieffo, Montorfano, Carlino, Michev, Corvaja, Briguori, and Colombo); Mediolanum Cardio Research, Milan, Italy (Dr Sangiorgi); Department of Cardiology, Klinikum Siegburg Rhein-Sieg GmbH, Siegburg, Germany (Drs Schmidt, Gerckens, and Grube); and Institute of Medical Statistics and Biometry, University of Milan, Milan, Italy (Dr Bonizzoni).

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JAMA. 2005;293(17):2126-2130. doi:10.1001/jama.293.17.2126.
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Context Traditionally, stent thrombosis has been regarded as a complication of percutaneous coronary interventions during the first 30 postprocedural days. However, delayed endothelialization associated with the implantation of drug-eluting stents may extend the risk of thrombosis beyond 30 days. Data are limited regarding the risks and the impact of this phenomenon outside clinical trials.

Objective To evaluate the incidence, predictors, and clinical outcome of stent thrombosis after implantation of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice.

Design, Setting, and Patients Prospective observational cohort study conducted at 1 academic hospital and 2 community hospitals in Germany and Italy. A total of 2229 consecutive patients underwent successful implantation of sirolimus-eluting (1062 patients, 1996 lesions, 2272 stents) or paclitaxel-eluting (1167 patients, 1801 lesions, 2223 stents) stents between April 2002 and January 2004.

Interventions Implantation of a drug-eluting stent (sirolimus or paclitaxel). All patients were pretreated with ticlopidine or clopidogrel and aspirin. Aspirin was continued indefinitely and clopidogrel or ticlopidine for at least 3 months after sirolimus-eluting and for at least 6 months after paclitaxel-eluting stent implantation.

Main Outcome Measures Subacute thrombosis (from procedure end through 30 days), late thrombosis (>30 days), and cumulative stent thrombosis.

Results At 9-month follow-up, 29 patients (1.3%) had stent thrombosis (9 [0.8%] with sirolimus and 20 [1.7%] with paclitaxel; P = .09). Fourteen patients had subacute thrombosis (0.6%) and 15 patients had late thrombosis (0.7%). Among these 29 patients, 13 died (case fatality rate, 45%). Independent predictors of stent thrombosis were premature antiplatelet therapy discontinuation (hazard ratio [HR],  89.78; 95% CI, 29.90-269.60; P<.001), renal failure (HR,  6.49; 95% CI, 2.60-16.15; P<.001), bifurcation lesions (HR,  6.42; 95% CI, 2.93-14.07; P<.001), diabetes (HR,  3.71; 95% CI, 1.74-7.89; P = .001), and a lower ejection fraction (HR,  1.09; 95% CI, 1.05-1.36; P<.001 for each 10% decrease).

Conclusions The cumulative incidence of stent thrombosis 9 months after successful drug-eluting stent implantation in consecutive “real-world” patients was substantially higher than the rate reported in clinical trials. Premature antiplatelet therapy discontinuation, renal failure, bifurcation lesions, diabetes, and low ejection fraction were identified as predictors of thrombotic events.

Despite major improvements in antiplatelet therapy, thrombotic events remain the primary cause of death after percutaneous coronary interventions.1,2 Sirolimus-eluting stents and polymer-based paclitaxel-eluting stents have been shown to reduce neointimal hyperplasia and risk of restenosis without increasing the risk of stent thrombosis.37 Operators are now using drug-eluting stents for a wide variety of clinical and anatomic situations, many of which have not been evaluated in randomized studies.810 We analyzed the incidence, predictors, and clinical outcome of stent thrombosis at 9-month follow-up in an observational cohort study.

We identified 2229 consecutive patients who underwent successful implantation with sirolimus-eluting stents (1062 patients, 1996 lesions, 2272 stents) or paclitaxel-eluting stents (1167 patients, 1801 lesions, 2223 stents) between April 2002 and January 2004. Patients were treated at 2 community hospitals or 1 academic hospital in Germany and Italy. Patients with ST-elevation acute myocardial infarction (MI) less than 48 hours before the procedure, with intraprocedural stent thrombosis, and those treated with both types of stents were excluded. All patients were pretreated with ticlopidine or clopidogrel and aspirin; a loading dose of 300 mg of clopidogrel was given to patients not previously taking the agent. Aspirin was continued indefinitely and clopidogrel or ticlopidine for at least 3 months after sirolimus-eluting stent implantation and for at least 6 months after paclitaxel-eluting stent implantation. Stent implantation methods have been described previously.11 Glycoprotein IIb/IIIa inhibitors were administered at the physician’s discretion. Standard qualitative and quantitative analyses and definitions were used for the angiographic analysis.12

All patients signed an informed consent document and local institutional review boards approved the study as planned.

Clinical Definitions and Follow-up

Stent thrombosis was determined as the occurrence of any of the following events: angiographic documentation of partial or total stent occlusion detected within 30 days of the procedure (an acute clinical ischemic event in addition to angiographic documentation had to be present when the event occurred after 30 days), or sudden cardiac death or postprocedural MI after successful stent implantation not clearly attributable to another coronary lesion. Stent thrombosis cases were categorized according to the timing of occurrence into subacute (from procedure end through 30 days) and late (>30 days).

Major adverse cardiac events were defined as death (all-cause), Q-wave MI, target lesion revascularization, and target vessel revascularization.

Statistical Analysis

Differences in proportions were tested with the χ2 or Fisher exact test. SAS version 8.2 (SAS Institute Inc, Cary, NC) was used for data analysis.

A total sample of 2300 observations was computed to achieve 80% power at a 2-sided .05 significance level to detect a hazard ratio (HR) equal to or greater than 3.0 with a Cox regression of the log HR on a binary risk factor with a 25% or greater prevalence. The sample size was adjusted for an anticipated event rate of 1.5%.

Relationships of event incidence to covariates were investigated with univariate Cox regression models. The proportional hazard assumption was checked for all screened covariates and no relevant violations were found. The predictive robustness of univariate findings was subsequently tested by means of a bootstrap subset selection method in which multivariable Cox regression analysis using a stepwise elimination process was repeated for each of 1000 bootstrap samples.13 The relative frequency of selection of “important” variables was used as a criterion for inclusion of predictors in the final multivariable model. Variables were retained if the selection frequency of the bootstrap samples was at least 50% or if they were clinically relevant. Because of the small absolute number of events, we performed an internal validation process to test model adequacy and quantify “overfitting.”14

The proportion of total variability was estimated by means of the Nagelkerke Index (pseudo R2), which was calculated when the models were fitted to 1000 bootstrap replications (training sample) and to the original data (test sample). The Nagelkerke Index obtained from each bootstrap sample was then subtracted from the initial index value of the original population. The average of the differences was considered as a measure of optimism in the model fit, where optimism is the proportion of variability ascribed to overfitting. Finally, a corrected index was calculated by subtracting the average of the optimism estimates from the original Nagelkerke Index. The estimates of slope shrinkage, which were used to identify overparameterized models, were obtained for the multivariable models using the same bootstrapping validation process. Thus we were reassured that, although based on few events, overfitting did not substantially bias our final model.

Baseline Characteristics and In-Hospital Outcomes

Baseline, angiographic, and procedural characteristics are shown in Table 1. All stents were deployed successfully. There were no significant differences between the 2 stent groups regarding procedural complications and in-hospital outcome. The rates for Q-wave and non–Q-wave MI were 0.3% and 9%, respectively. There were 4 in-hospital deaths, of which 2 were determined to be caused by stent thrombosis.

Table Graphic Jump LocationTable 1. Baseline Clinical, Angiographic, and Procedural Characteristics According to Stent Type
Incidence, Timing, Presentation, and Clinical Outcome of Stent Thrombosis

At 9-month follow-up (available in all patients), 29 patients (1.3%) had stent thrombosis (9 [0.8%] in the sirolimus group and 20 [1.7%] in the paclitaxel group; P = .09). Fourteen patients had subacute thrombosis (0.6%), 4 in the sirolimus group and 10 in the paclitaxel group (0.4% vs 0.8%; P = .19) and 15 patients had late thrombosis (0.7%), 5 in the sirolimus group and 10 in the paclitaxel group (0.5% vs 0.8%; P = .30).

A total of 71% (10/14) of the subacute cases occurred within 1 week of the procedure (median, 4 days) and 53% (8/15) of the late thrombosis cases occurred within 3 months of the procedure (median, 57 days). Seven cases (24%) presented as death, 20 (69%) as nonfatal MI, and 2 (7%) as unstable angina.

At follow-up the case-fatality rate—including death at presentation—was 45% (13/29). Angiographic documentation of thrombosis was available in 12 of the 22 patients (55%) with stent thrombosis (including both patients that presented with unstable angina) that did not present with death. In-hospital data were available for all patients who presented with acute MI and had no angiographic evidence of stent thrombosis.

At 9-month follow-up, target lesion revascularization was performed in 141 patients (6.3%) (58 [5.5%] in the sirolimus group vs 83 [7.1%] in the paclitaxel group; P = .13). Major adverse cardiac events occurred in 242 patients (10.8%) (109 [10.3%] in the sirolimus group vs 133 [11.4%] in the paclitaxel group; P = .42).

Predictors of Stent Thrombosis

The incidence of stent thrombosis according to selected patient characteristics and the univariate predictors of cumulative stent thrombosis are shown in Table 2. Five of 17 patients with premature antiplatelet therapy discontinuation had stent thrombosis; in 1 of them only clopidogrel was discontinued. Independent predictors of subacute, late, and cumulative stent thrombosis are shown in Table 3. The key predictors of stent thrombosis were premature antiplatelet therapy discontinuation, renal failure, bifurcation lesions, diabetes, and low ejection fraction. For subacute thrombosis, stent length was also a predictor: for each 1-mm increase in length, there was 1.03 times greater risk of thrombosis.

Table Graphic Jump LocationTable 2. Univariate Predictors of Cumulative Stent Thrombosis
Table Graphic Jump LocationTable 3. Independent Predictors of Stent Thrombosis

In a large cohort of consecutive patients undergoing drug-eluting stent implantation, we noted a 9-month cumulative stent thrombosis incidence of 1.3%, substantially higher than rates reported in major clinical trials (0.4% at 1 year for sirolimus and 0.6% at 9 months for paclitaxel).3,5 With widespread availability of drug-eluting stents, the scope of percutaneous coronary intervention has been expanded to more complex lesions and patients. In our study, 27% of the population had diabetes and 79% of the lesions were complex. The clinical consequences of stent thrombosis were severe, with a case-fatality rate of 45%.

Similar to previous reports of both bare-metal stents2,16,17 and drug-eluting stents,18,19 our study found that premature discontinuation of antiplatelet therapy was the most important predictor of stent thrombosis after implantation. Thrombosis occurred in 29% of patients who prematurely discontinued dual antiplatelet therapy, making treatment adherence of paramount importance. Nonetheless, the absolute numbers of events in our cohort were small, leading to wide confidence intervals for estimation of effect magnitude.

In addition to premature discontinuation of antiplatelet therapy, other key predictors of stent thrombosis were renal failure, bifurcation lesions, diabetes, low ejection fraction, and, for subacute thrombosis, stent length.

Renal failure has been linked to cardiac disease with microvascular and metabolic abnormalities that may predispose to thrombus formation.20,21 Renal failure also has been associated by numerous studies with an increased mortality rate despite successful coronary intervention.2224

Regarding bifurcational lesion location, pathology studies have suggested that arterial branch points are foci of low shear and low flow velocity and are sites predisposed to the development of atherosclerotic plaque, thrombus, and inflammation.2527 The observed associations of diabetes,2832 low ejection fraction,2,33 and stent length2 with stent thrombosis are also consistent with previous reports.

In our study, stent type did not emerge as an independent predictor of thrombosis. Of concern, however, we found an almost double incidence of stent thrombosis after paclitaxel compared with sirolimus stent implantation. These findings are consistent with those of the ISAR-DESIRE (Intracoronary Stenting and Antithrombotic Regimen–Drug-Eluting Stents for In-Stent Restenosis) trial of drug-eluting stents for in-stent restenosis, in which sirolimus-eluting stents tended to be associated with a better outcome than paclitaxel-eluting stents.6 However, without larger numbers it is difficult to make firmconclusions; subsequent randomized trials will be critically important.

A limitation of the current study was the lack of angiographic documentation in all cases adjudicated as stent thrombosis. Nevertheless, the definition of stent thrombosis that we proposed is similar to the one used in important recent studies extended beyond 30 days.3,19

In conclusion, the incidence of stent thrombosis at 9 months after successful drug-eluting stent implantation in consecutive real-world patients was 1.3%. Premature antiplatelet therapy discontinuation, bifurcation lesions, and low ejection fraction were identified as independent predictors of subacute, late, and cumulative stent thrombosis. In addition, stent length was also recognized as a predictor of subacute thrombosis, and renal failure and diabetes as predictors of both subacute and cumulative stent thrombosis. The clinical consequences were death in 45% of patients and nonfatal MI in the majority of the others.

Corresponding Author: Antonio Colombo, MD, EMO Centro Cuore Columbus, 48 Via M Buonarroti, 20145 Milan, Italy (info@emocolumbus.it).

Author Contributions: Dr Colombo had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Iakovou, Schmidt, Colombo.

Acquisition of data: Ge, Sangiorgi, Stankovic, Airoldi, Chieffo, Montorfano, Carlino, Michev, Corvaja, Gerckens, Grube.

Analysis and interpretation of data: Iakovou, Bonizzoni, Briguori.

Drafting of the manuscript: Iakovou, Colombo.

Critical revision of the manuscript for important intellectual content: Schmidt, Bonizzoni, Ge, Sangiorgi, Stankovic, Airoldi, Chieffo, Montorfano, Carlino, Michev, Corvaja, Briguori, Gerckens, Grube.

Statistical analysis: Iakovou, Bonizzoni.

Study supervision: Schmidt, Sangiorgi, Chieffo, Montorfano, Carlino, Briguori, Gerckens, Grube, Colombo.

Financial Disclosures: None reported.

Previous Presentation: This study was presented at the American Heart Association Scientific Sessions; November 7-10, 2004; New Orleans, La.

Schomig A, Neumann FJ, Kastrati A.  et al.  A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents.  N Engl J Med. 1996;334:1084-1089
PubMed   |  Link to Article
Moussa I, Di Mario C, Reimers B, Akiyama T, Tobis J, Colombo A. Subacute stent thrombosis in the era of intravascular ultrasound-guided coronary stenting without anticoagulation: frequency, predictors and clinical outcome.  J Am Coll Cardiol. 1997;29:6-12
PubMed   |  Link to Article
Stone GW, Ellis SG, Cox DA.  et al.  A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease.  N Engl J Med. 2004;350:221-231
PubMed   |  Link to Article
Morice MC, Serruys PW, Sousa JE.  et al.  A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization.  N Engl J Med. 2002;346:1773-1780
PubMed   |  Link to Article
Moses JW, Leon MB, Popma JJ.  et al.  Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery.  N Engl J Med. 2003;349:1315-1323
PubMed   |  Link to Article
Kastrati A, Mehilli J, von Beckerath N.  et al.  Sirolimus-eluting stent or paclitaxel-eluting stent vs balloon angioplasty for prevention of recurrences in patients with coronary in-stent restenosis: a randomized controlled trial.  JAMA. 2005;293:165-171
PubMed   |  Link to Article
Ardissino D, Cavallini C, Bramucci E.  et al.  Sirolimus-eluting vs uncoated stents for prevention of restenosis in small coronary arteries: a randomized trial.  JAMA. 2004;292:2727-2734
PubMed   |  Link to Article
Colombo A, Iakovou I. Drug-eluting stents: the new gold standard for percutaneous coronary revascularisation.  Eur Heart J. 2004;25:895-897
PubMed   |  Link to Article
Iakovou I, Sangiorgi GM, Stankovic G.  et al.  Effectiveness of sirolimus-eluting stent implantation for treatment of in-stent restenosis after brachytherapy failure.  Am J Cardiol. 2004;94:351-354
PubMed   |  Link to Article
Iakovou I, Ge L, Michev I.  et al.  Clinical and angiographic outcome after sirolimus-eluting stent implantation in aorto-ostial lesions.  J Am Coll Cardiol. 2004;44:967-971
PubMed   |  Link to Article
Colombo A, Orlic D, Stankovic G.  et al.  Preliminary observations regarding angiographic pattern of restenosis after rapamycin-eluting stent implantation.  Circulation. 2003;107:2178-2180
PubMed   |  Link to Article
Lansky AJ, Dangas G, Mehran R.  et al.  Quantitative angiographic methods for appropriate end-point analysis, edge-effect evaluation, and prediction of recurrent restenosis after coronary brachytherapy with gamma irradiation.  J Am Coll Cardiol. 2002;39:274-280
PubMed   |  Link to Article
Sauerbrei W, Schumacher M. A bootstrap resampling procedure for model building: application to the Cox regression model.  Stat Med. 1992;11:2093-2109
PubMed   |  Link to Article
Harrell FE Jr, Lee KL, Mark DB. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors.  Stat Med. 1996;15:361-387
PubMed   |  Link to Article
Ellis SG, Vandormael MG, Cowley MJ.  et al. Multivessel Angioplasty Prognosis Study Group.  Coronary morphologic and clinical determinants of procedural outcome with angioplasty for multivessel coronary disease: implications for patient selection.  Circulation. 1990;82:1193-1202
PubMed   |  Link to Article
Cheneau E, Leborgne L, Mintz GS.  et al.  Predictors of subacute stent thrombosis: results of a systematic intravascular ultrasound study.  Circulation. 2003;108:43-47
PubMed   |  Link to Article
Cutlip DE, Baim DS, Ho KK.  et al.  Stent thrombosis in the modern era: a pooled analysis of multicenter coronary stent clinical trials.  Circulation. 2001;103:1967-1971
PubMed   |  Link to Article
McFadden EP, Stabile E, Regar E.  et al.  Late thrombosis in drug-eluting coronary stents after discontinuation of antiplatelet therapy.  Lancet. 2004;364:1519-1521
PubMed   |  Link to Article
Jeremias A, Sylvia B, Bridges J.  et al.  Stent thrombosis after successful sirolimus-eluting stent implantation.  Circulation. 2004;109:1930-1932
PubMed   |  Link to Article
Herzog CA, Ma JZ, Collins AJ. Comparative survival of dialysis patients in the United States after coronary angioplasty, coronary artery stenting, and coronary artery bypass surgery and impact of diabetes.  Circulation. 2002;106:2207-2211
PubMed   |  Link to Article
Amann K, Ritz E. Cardiac disease in chronic uremia: pathophysiology.  Adv Ren Replace Ther. 1997;4:212-224
PubMed
Gruberg L, Mintz GS, Mehran R.  et al.  The prognostic implications of further renal function deterioration within 48 h of interventional coronary procedures in patients with pre-existent chronic renal insufficiency.  J Am Coll Cardiol. 2000;36:1542-1548
PubMed   |  Link to Article
Rubenstein MH, Harrell LC, Sheynberg BV, Schunkert H, Bazari H, Palacios IF. Are patients with renal failure good candidates for percutaneous coronary revascularization in the new device era?  Circulation. 2000;102:2966-2972
PubMed   |  Link to Article
Mehran R, Aymong ED, Nikolsky E.  et al.  A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation.  J Am Coll Cardiol. 2004;44:1393-1399
PubMed
Glagov S, Zarins C, Giddens DP, Ku DN. Hemodynamics and atherosclerosis. Insights and perspectives gained from studies of human arteries.  Arch Pathol Lab Med. 1988;112:1018-1031
PubMed
Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ. Compensatory enlargement of human atherosclerotic coronary arteries.  N Engl J Med. 1987;316:1371-1375
PubMed   |  Link to Article
Farb A, Burke AP, Kolodgie FD, Virmani R. Pathological mechanisms of fatal late coronary stent thrombosis in humans.  Circulation. 2003;108:1701-1706
PubMed   |  Link to Article
Schuhlen H, Kastrati A, Dirschinger J.  et al.  Intracoronary stenting and risk for major adverse cardiac events during the first month.  Circulation. 1998;98:104-111
PubMed   |  Link to Article
Moreno PR, Murcia AM, Palacios IF.  et al.  Coronary composition and macrophage infiltration in atherectomy specimens from patients with diabetes mellitus.  Circulation. 2000;102:2180-2184
PubMed   |  Link to Article
Creager MA, Luscher TF, Cosentino F, Beckman JA. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I.  Circulation. 2003;108:1527-1532
PubMed   |  Link to Article
Lyon CJ, Hsueh WA. Effect of plasminogen activator inhibitor-1 in diabetes mellitus and cardiovascular disease.  Am J Med. 2003;115:(suppl 8A)  62S-68S
PubMed   |  Link to Article
Nesto RW. Correlation between cardiovascular disease and diabetes mellitus: current concepts.  Am J Med. 2004;116:(suppl 5A)  11S-22S
PubMed   |  Link to Article
Chieffo A, Bonizzoni E, Orlic D.  et al.  Intraprocedural stent thrombosis during implantation of sirolimus-eluting stents.  Circulation. 2004;109:2732-2736
PubMed   |  Link to Article

Figures

Tables

Table Graphic Jump LocationTable 1. Baseline Clinical, Angiographic, and Procedural Characteristics According to Stent Type
Table Graphic Jump LocationTable 2. Univariate Predictors of Cumulative Stent Thrombosis
Table Graphic Jump LocationTable 3. Independent Predictors of Stent Thrombosis

References

Schomig A, Neumann FJ, Kastrati A.  et al.  A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents.  N Engl J Med. 1996;334:1084-1089
PubMed   |  Link to Article
Moussa I, Di Mario C, Reimers B, Akiyama T, Tobis J, Colombo A. Subacute stent thrombosis in the era of intravascular ultrasound-guided coronary stenting without anticoagulation: frequency, predictors and clinical outcome.  J Am Coll Cardiol. 1997;29:6-12
PubMed   |  Link to Article
Stone GW, Ellis SG, Cox DA.  et al.  A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease.  N Engl J Med. 2004;350:221-231
PubMed   |  Link to Article
Morice MC, Serruys PW, Sousa JE.  et al.  A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization.  N Engl J Med. 2002;346:1773-1780
PubMed   |  Link to Article
Moses JW, Leon MB, Popma JJ.  et al.  Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery.  N Engl J Med. 2003;349:1315-1323
PubMed   |  Link to Article
Kastrati A, Mehilli J, von Beckerath N.  et al.  Sirolimus-eluting stent or paclitaxel-eluting stent vs balloon angioplasty for prevention of recurrences in patients with coronary in-stent restenosis: a randomized controlled trial.  JAMA. 2005;293:165-171
PubMed   |  Link to Article
Ardissino D, Cavallini C, Bramucci E.  et al.  Sirolimus-eluting vs uncoated stents for prevention of restenosis in small coronary arteries: a randomized trial.  JAMA. 2004;292:2727-2734
PubMed   |  Link to Article
Colombo A, Iakovou I. Drug-eluting stents: the new gold standard for percutaneous coronary revascularisation.  Eur Heart J. 2004;25:895-897
PubMed   |  Link to Article
Iakovou I, Sangiorgi GM, Stankovic G.  et al.  Effectiveness of sirolimus-eluting stent implantation for treatment of in-stent restenosis after brachytherapy failure.  Am J Cardiol. 2004;94:351-354
PubMed   |  Link to Article
Iakovou I, Ge L, Michev I.  et al.  Clinical and angiographic outcome after sirolimus-eluting stent implantation in aorto-ostial lesions.  J Am Coll Cardiol. 2004;44:967-971
PubMed   |  Link to Article
Colombo A, Orlic D, Stankovic G.  et al.  Preliminary observations regarding angiographic pattern of restenosis after rapamycin-eluting stent implantation.  Circulation. 2003;107:2178-2180
PubMed   |  Link to Article
Lansky AJ, Dangas G, Mehran R.  et al.  Quantitative angiographic methods for appropriate end-point analysis, edge-effect evaluation, and prediction of recurrent restenosis after coronary brachytherapy with gamma irradiation.  J Am Coll Cardiol. 2002;39:274-280
PubMed   |  Link to Article
Sauerbrei W, Schumacher M. A bootstrap resampling procedure for model building: application to the Cox regression model.  Stat Med. 1992;11:2093-2109
PubMed   |  Link to Article
Harrell FE Jr, Lee KL, Mark DB. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors.  Stat Med. 1996;15:361-387
PubMed   |  Link to Article
Ellis SG, Vandormael MG, Cowley MJ.  et al. Multivessel Angioplasty Prognosis Study Group.  Coronary morphologic and clinical determinants of procedural outcome with angioplasty for multivessel coronary disease: implications for patient selection.  Circulation. 1990;82:1193-1202
PubMed   |  Link to Article
Cheneau E, Leborgne L, Mintz GS.  et al.  Predictors of subacute stent thrombosis: results of a systematic intravascular ultrasound study.  Circulation. 2003;108:43-47
PubMed   |  Link to Article
Cutlip DE, Baim DS, Ho KK.  et al.  Stent thrombosis in the modern era: a pooled analysis of multicenter coronary stent clinical trials.  Circulation. 2001;103:1967-1971
PubMed   |  Link to Article
McFadden EP, Stabile E, Regar E.  et al.  Late thrombosis in drug-eluting coronary stents after discontinuation of antiplatelet therapy.  Lancet. 2004;364:1519-1521
PubMed   |  Link to Article
Jeremias A, Sylvia B, Bridges J.  et al.  Stent thrombosis after successful sirolimus-eluting stent implantation.  Circulation. 2004;109:1930-1932
PubMed   |  Link to Article
Herzog CA, Ma JZ, Collins AJ. Comparative survival of dialysis patients in the United States after coronary angioplasty, coronary artery stenting, and coronary artery bypass surgery and impact of diabetes.  Circulation. 2002;106:2207-2211
PubMed   |  Link to Article
Amann K, Ritz E. Cardiac disease in chronic uremia: pathophysiology.  Adv Ren Replace Ther. 1997;4:212-224
PubMed
Gruberg L, Mintz GS, Mehran R.  et al.  The prognostic implications of further renal function deterioration within 48 h of interventional coronary procedures in patients with pre-existent chronic renal insufficiency.  J Am Coll Cardiol. 2000;36:1542-1548
PubMed   |  Link to Article
Rubenstein MH, Harrell LC, Sheynberg BV, Schunkert H, Bazari H, Palacios IF. Are patients with renal failure good candidates for percutaneous coronary revascularization in the new device era?  Circulation. 2000;102:2966-2972
PubMed   |  Link to Article
Mehran R, Aymong ED, Nikolsky E.  et al.  A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation.  J Am Coll Cardiol. 2004;44:1393-1399
PubMed
Glagov S, Zarins C, Giddens DP, Ku DN. Hemodynamics and atherosclerosis. Insights and perspectives gained from studies of human arteries.  Arch Pathol Lab Med. 1988;112:1018-1031
PubMed
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