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European Heart Journal Advance Access originally published online on November 15, 2006
European Heart Journal 2006 27(23):2815-2822; doi:10.1093/eurheartj/ehl385
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© The European Society of Cardiology 2006. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Cause of death with bare metal and sirolimus-eluting stents{dagger}

David R. Holmes, Jr1,*, Jeffrey W. Moses2, Joachim Schofer3, Marie-Claude Morice4, Erick Schampaert5 and Martin B. Leon2

1 Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
2 Center for Interventional Vascular Therapy, Columbia University Medical Center, New York, NY, USA
3 Hamburg University Cardiovascular Center, Hamburg, Germany
4 Institut Cardiovasculaire Paris Sud, Institute Hospitalier Jacques Cartier, Massy, France
5 Cardiac Catheterization Laboratories, Division of Cardiology, Hôpital du Sacré-Coeur de Montréal, Montréal, Québec, Canada

Received 27 July 2006; revised 9 October 2006; accepted 31 October 2006; online publish-ahead-of-print 15 November 2006.

* Corresponding author. Consultant, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

See page 2737 for the editorial comment on this article (doi:10.1093/eurheartj/ehl378)


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Limitations
 Conclusions
 Acknowledgement
 References
 
Aims Although drug-eluting stents have assumed a dominant role in interventional cardiology, concern has been raised about the potential for long-term adverse outcomes, including death. The aim of the present study was to compare the incidence and cause of death between patients who received sirolimus-eluting or bare metal stents.

Methods and results An integrated analysis was performed on 1748 patients enrolled in four prospective double-blind trials that randomly assigned patients to receive either a sirolimus-eluting or a bare metal stent for treatment of a single de novo coronary stenosis. During a mean follow-up of 2.6±0.6 years, 64 patients (3.7%) died. Total mortality was 3.2% among 870 bare metal stent patients and 4.1% among 878 sirolimus-eluting stent patients (P=0.37); there was no difference in cardiac mortality (1.4 vs. 1.3%; P=0.55) or causes of death between these two groups. The predominant cause of death was non-cardiac. Cardiac death was most frequently assigned owing to unwitnessed death. Death due to acute myocardial infarction, congestive heart failure, and stent thrombosis occurred infrequently.

Conclusion At a mean follow-up of 2.6 years in percutaneous coronary intervention patients, the predominant cause of death was non-cardiac. There was no significant difference in either the frequency or the cause of death with implantation of either sirolimus-eluting or bare metal stents.

Key Words: Cardiac death • Drug-eluting stents • Follow-up mortality


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 Limitations
 Conclusions
 Acknowledgement
 References
 
The use of drug-eluting coronary stents has dramatically changed the field of interventional cardiology and has become the dominant percutaneous interventional strategy based on the results of randomized clinical trials and registries. Two stents, the sirolimus-eluting CYPHER (Cordis Corp., Miami, FL, USA) and the paclitaxel-eluting TAXUS (Boston Scientific Corp., Natick, MA, USA), have been shown to decrease both angiographic and clinical restenosis rates.1–8 This improvement in clinical and angiographic restenosis has resulted in the use of these stents in 80–90% of all percutaneous coronary interventions. Concern has been raised, however, about the potential for delayed subacute and late thrombosis and death.9–14 In registry experiences, the risk of thrombosis extends for a longer period with drug-eluting stents than with bare metal stents. Iakovou et al.9 reported on 29 patients with stent thrombosis at follow-up of 9 months; these 29 patients represented 1.3% of the 2229 consecutive registry patients who received drug-eluting stents between 2002 and 2004. To assess late death, longer-term follow-up is required. The present report focuses on late death in four randomized multicentre clinical trials of sirolimus-eluting stents vs. bare metal stents.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 Limitations
 Conclusions
 Acknowledgement
 References
 
The basis of the present analysis is four prospective, randomized, double-blind, institutional review board-approved clinical trials (Table 1): RAVEL1,2 [randomized double-blind study with the sirolimus-eluting Bx VELOCITY (Cordis Corp.) balloon-expandable stent in the treatment of patients with de novo coronary artery lesions], SIRIUS3,4 (sirolimus-eluting stents in de novo native coronary artery lesions), E-SIRIUS5 (European study of sirolimus-eluting stents in de novo native coronary artery lesions), and C-SIRIUS6 (Canadian study of sirolimus-eluting stents in de novo native coronary artery lesions). Each study included patients with a single de novo lesion in native coronary arteries who were randomly assigned to receive implanted sirolimus-eluting Bx VELOCITY stents (SESs) or Bx VELOCITY bare metal stents (BMSs). Neither the investigator nor the patient knew which stents were implanted because they are visually identical and were packed in identical containers.


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  		Table 1 Randomized trials of sirolimus-eluting stents vs. bare metal stents

 
The coordination and data management of the three SIRIUS studies were performed by the Harvard Clinical Research Institute (Boston, MA, USA), and the data of the RAVEL study were managed by Cardialysis BV (Rotterdam, the Netherlands). The 8-month angiographic follow-up data of the three SIRIUS studies were assessed at the Brigham and Women's Angiographic Core Laboratory (Boston, MA, USA), whereas the 6-month quantitative coronary angiographic follow-up data of RAVEL were processed by the Cardialysis BV core laboratory. All patients will be followed-up clinically for 5 years. Major clinical events were adjudicated by an independent clinical events committee.

The design of each trial is shown in Table 1. In addition to the primary endpoints for each trial, clinical endpoints included death, myocardial infarction, repeat percutaneous coronary intervention, coronary artery bypass surgery, and stent thrombosis. There was variability in the antiplatelet therapy regimens used after hospital discharge.

In each of these trials, follow-up clinical data were available for at least 2 years. Information on the circumstances of the deaths was obtained from each of the sites and narratives were developed. These narratives were reviewed by the clinical events committee for the trials and also by the principal author of this manuscript (D.R.H.). The cause of death was then classified as ‘cardiac’ or ‘non-cardiac’. If the cause of death was unknown, it was attributed to cardiac causes. Cardiac death was further subdivided into death related to acute myocardial infarction, congestive heart failure, stent thrombosis, or a revascularization procedure. Each documented non-cardiac cause of death was also tabulated. The timing of death relative to the index procedure was tabulated. In addition, the results of intervening follow-up angiography were evaluated for the presence of either in-stent or in-lesion restenosis (defined as angiographic restenosis >50%) as well as for the occurrence of either target vessel or target lesion revascularization. This integrated analysis was not pre-specified in the protocols for these trials.

Statistical analysis
All studies used intention-to-treat analyses. Entire groups of patients who died were compared with patients who survived, and patients who received the SES were compared with patients who received the BMS.

The two-tailed t-test was used to compare the treatment difference, the homogeneity of the variance was tested, and the t-test P-value and the 95% confidence interval of the mean difference were presented accordingly, in addition to the summaries of mean and standard deviation of each treatment group. For the categorical variables, the percentage difference, the 95% confidence interval, and the two-sided Fisher exact test P-value were reported. The Kaplan–Meier method was used to evaluate survival for patients with SESs and for patients with BMSs according to the cause of death, with differences between event-free survival curves assessed by the log-rank test. A conventional statistical significance level of 5% (P<0.05) was used. All statistical analyses were performed using SAS Version 8.2 (SAS Institute, Cary, NC, USA).

To explore the association between time-to-death and patient demographics and lesion characteristics, a univariable analysis was performed first by using the Cox proportional hazards regression model with time-to-death as the dependent variable and each of the patient demographic and lesion characteristic variables as covariates. The covariate coefficient, standard error, {chi}2 statistic, hazard ratio, and 95% confidence interval of each covariate were summarized. A multivariable analysis was then performed with the Cox proportional hazards regression model. A stepwise selection procedure was used with an entry criterion of 0.20 and a stay criterion of 0.10. The covariate coefficient, standard error, {chi}2 statistic, hazard ratio, and 95% confidence interval, using selected covariates that were included in the multivariable Cox regression model, were presented.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 Limitations
 Conclusions
 Acknowledgement
 References
 
A total of 1748 patients from these four trials were included in this analysis: 878 received the SES and 870 received the BMS. Follow-up clinical data compliance over 2 years averaged 96.4%. The mean follow-up was 2.6±0.6 years. Poolability of these data is supported by the similar trial designs and the comparable patient demographics, lesion characteristics, and major adverse cardiac events across the four trials within both the sirolimus-eluting and the control groups.1–6

There were few significant differences in baseline clinical characteristics between patients who died and those who survived during 2.6±0.6 years of follow-up (Table 2). In the SES patients, these clinical characteristics included mean age at the index procedure, 69.9±9.5 vs. 61.5±11.1 years (P<0.001); history of congestive heart failure, 13.9 vs. 5.7% (P=0.01); and less frequent single-vessel disease, 44.4 vs. 62.1% (P=0.04). In the BMS patients, the only significant difference was age: 66.6±9.5 years among patients who died vs. 61.8±10.7 years among patients who survived (P=0.02). No other significantly different baseline characteristics were found.


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  		Table 2 Baseline characteristics of patients treated with sirolimus-eluting stents or control bare metal stents by survival statusa

 
There were few differences in baseline angiographic findings between patients who died and those who survived during 2.6±0.6 years of follow-up. In the SES patients, LAD location predominated (in 41.7% of the patients who died and in 46.8% of the patients who survived; P=0.61), and typically the stenosis was in the mid-portion of the vessel. Patients who died had a higher proportion of shorter lesions (<10 mm) treated than those who survived (44.4 vs. 26.8%; P=0.03). In the BMS patients, the only significant differences were that patients who died, compared with patients who survived, had a higher proportion of ulcerated lesions (17.4 vs. 5.7%; P=0.046) and aneurysm lesions (17.4 vs. 4.0%; P=0.02).

There were few differences in procedural characteristics between patients who died and survivors (Table 3). In the SES group, there were no significant differences. In the control BMS group, two variables were significantly different: patients who died were less likely to have received a glycoprotein IIb/IIIa agent (21.4 vs. 44.1%; P=0.02) and were less likely to have received a 3.5-mm stent (7.7 vs. 26.3%; P=0.01), although there was no significant difference in baseline minimal luminal diameter (MLD).


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  		Table 3 Selected procedural characteristics of patients treated with sirolimus-eluting stents or control bare metal stents by survival statusa

 
Eight-month quantitative angiographic follow-up data were available for 28 patients who died and for 1082 patients who survived (including both SES patients and BMS patients). Overall, in the combined group of SES and BMS patients, there was no difference in binary restenosis (28.6% for patients who died vs. 23.7% for patients who survived; P=0.51). There was also no significant difference in the in-stent MLD or the stenosis diameter between those who died and the survivors. There was, however, a difference in MLD at the proximal edge; in patients who died, MLD was 1.98±0.80 mm and in survivors, 2.42±0.68 mm (P=0.001). The late loss (i.e. the difference between MLD immediately after the procedure and MLD at follow-up) at the location was correspondingly greater in patients who died than in survivors (0.52±0.71 vs. 0.24±0.55 mm; P=0.01).

During a mean follow-up of 31.6±7.3 months, total mortality as well as the cause of death (i.e. cardiac vs. non-cardiac) varied among the trials (Table 4). There was no difference in cardiac mortality between the two groups, with deaths occurring in 14 BMS and 11 SES patients (P=0.55). Total mortality was numerically lower in the BMS patients (28/870; 3.2%) than in the SES patients (36/878; 4.1%), but the difference was not statistically significant (P=0.37). The numerical difference in total mortality was the result of an imbalance in non-cardiac deaths. Kaplan–Meier curves for all-cause mortality and cardiac mortality are shown in Figure 1.


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  		Table 4 3-year mortality among patients treated with sirolimus-eluting stents or control bare metal stents

 

Figure 3851
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  		Figure 1 Kaplan–Meier survival curves for all studies. Insets display the curves plotted on abbreviated y-axes. (A) Combined all-cause mortality. (B) Cardiac mortality. (C) Non-cardiac mortality. SES, sirolimus-eluting stent.

 
Cause of death was determined from case report forms and written narratives. Causes of cardiac and non-cardiac death are presented in Table 5. Approximately 60% of deaths (39/64) were from a non-cardiac cause. Nine causes of non-cardiac death were identified, with neurological disease (predominantly stroke), cancer, and sepsis being the most frequent aetiologies of non-cardiac death. A plot of time vs. the cumulative frequency of death (Figure 1C) indicates that the non-cardiac deaths for the BMS and SES groups overlap until ~180 days, when they separate and are subsequently higher (numerically but not statistically) for the SES group. Examination of death rates in each trial used in this integrated analysis demonstrates that this numerical excess of non-cardiac deaths is contributed by two smaller trials (RAVEL and C-SIRIUS) but not by the much larger SIRIUS trial.


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  		Table 5 Non-hierarchical list of causes of death

 
A specific cardiac cause of death was attributed in ~40% of deaths (25/64). The most common cause of cardiac death was unwitnessed death or death of unknown cause, denoted as ‘Unknown’ in Table 5 (12 of 14 in the BMS group and six of 11 in the SES group). Acute myocardial infarction and congestive heart failure were each identified as additional causes of cardiac death in two patients in each group. One death in the BMS group and three deaths in the SES group occurred with revascularization procedures.

Protocol-defined stent thrombosis was identified in 14 patients, five patients treated with BMS and nine patients treated with SES (P=0.42) (Figure 2). Although death occurred in one BMS and three SES patients (P=0.62) who experienced a stent thrombosis, only one death in each group was temporally related to the thrombotic event [i.e. the BMS patient died on day 30, the same day as the thrombosis, and the SES patients died on days 542 (three days after the thrombotic event), 802 (29 days after the thrombotic event), and 917 (907 days after the thrombotic event), respectively].


Figure 3852
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  		Figure 2 Rates of early (0–30 days) and late (31–720 days) stent thrombosis.

 
With use of the multiple Cox proportional hazards model, multivariable predictor analysis of all deaths identified that, after adjusting for other predictors, age, history of congestive heart failure, renal insufficiency, and smoking were associated with a greater hazard of death, whereas administration of a glycoprotein IIb/IIIa inhibitor and a history of percutaneous coronary intervention were associated with a lower hazard of death (Table 6). The type of stent (bare metal or sirolimus-eluting) was not identified in this model.


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  		Table 6 Predictors of death at any time (binary) by multiple Cox proportional hazards regression modela

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Limitations
 Conclusions
 Acknowledgement
 References
 
This study provides an important perspective on the cause of death for patients with cardiovascular disease. Although the main cause of death in Western civilizations is cardiovascular disease, this analysis indicates that the main cause of death in patients with cardiovascular disease entered into pivotal clinical trials and followed for a mean of 2.6 years is, in fact, non-cardiac. In patients in whom the cause of death was unknown, it was attributed to a cardiac cause. Despite a cardiac cause of death being attributed in 28% of cases owing to insufficient detail surrounding the patients’ deaths, ~60% of patients in this pooled analysis of four clinical studies had a documented non-cardiac cause of death. Whether this means that contemporary coronary intervention might, in fact, reduce the risk of cardiac death is uncertain but provocative.

The role of revascularization therapy in the prevention of cardiovascular death is complex and includes several potential factors, including a reduction in ischaemia, prevention of myocardial infarction, reduction in arrhythmias, and prevention or amelioration of congestive heart failure. Indeed, the extent to which any form of revascularization prevents cardiac death has been defined relatively poorly for patients who have stable coronary artery disease, with the exception of selected groups who have left main or significant left ventricular dysfunction.

In the initial Coronary Artery Surgery Study,15 coronary artery bypass graft (CABG) surgery, vs. medical therapy, was associated with a reduction in sudden cardiac death; similar findings were identified in a subsequent meta-analysis of patients with left main coronary artery stenosis.16 The effect of percutaneous revascularization on mortality is less clear17,18 because mortality rates were low in early trials, in which percutaneous transluminal coronary angioplasty (PTCA) was initially performed in patients with less extensive disease. The early randomized trials of PTCA vs. CABG surgery showed no difference in the intermediate-term mortality rate or the rate of myocardial infarction between the two revascularization strategies.17,18 In a recent meta-analysis of 13 trials19 involving 7964 eligible patients, neither strategy (PTCA or CABG) was associated with higher survival at 1, 3 or 8 years, with the exception of patients with multivessel disease who were treated with CABG surgery. They had a survival advantage at both 5 and 8 years.

In patients treated with stent implantation instead of CABG surgery, there was discordance in the results, depending on the specific patient population studied (i.e. diabetic vs. non-diabetic, presence or absence of left ventricular dysfunction, and severity and extent of multivessel disease).19–24 The effect of bare metal stents compared with conventional balloon angioplasty alone has also been studied.25–27 In a recent meta-analysis of 23 trials that enrolled 10 347 patients randomly assigned to PTCA or bare metal stent groups, there was no difference in mortality or myocardial infarction rate.27 Similarly, in the randomized trials of stent placement vs. CABG surgery, there was no difference in mortality or myocardial infarction rate in the short- and intermediate-term follow-up. Recently, a comparative analysis of two large non-randomized registries in New York, the Cardiac Surgery Reporting System and the Percutaneous Coronary Intervention Reporting System, after adjustment for risk factors, documented a survival benefit for patients with CAD who were treated surgically between 1999 and 2001, even though they were at higher risk at baseline.28

The use of drug-eluting stents has dramatically changed interventional cardiology and decreased angiographic and clinical restenosis rates. Despite this improvement in restenosis, no data have emerged that suggest drug-eluting stents might reduce death more than either bare metal stents or CABG. There are several confounding issues in the available data. First, death is uncommon in the relatively uncomplicated cases and lesions studied in pivotal studies. Secondly, restenosis is usually not associated with death, although in a preliminary autopsy study, two of four cases with drug-eluting stents and in-stent restenosis had non-occlusive thrombi.14 Thirdly, if very late subacute closure occurs more frequently with drug-eluting stents (the frequency of associated death was 45% in one series9), the mortality rate could even be increased. However, most of the randomized trials included relatively low-risk patients, so the signal (i.e. mortality) might be difficult to discern from these studies.

Other studies of drug-eluting stents reported rates of death of ~2–5% at the 12-month time point; death was most commonly reported as cardiac in nature.29,30 Rates of stent thrombosis were between 0.4 and 1.3%, and death from stent thrombosis occurred in 31–45% of patients.29–33 A meta-analysis of multiple percutaneous coronary intervention studies before the advent of drug-eluting stents suggests that in the first 12 months following the intervention, most cardiac events are related to the target lesion but after 12 months they more often result from progression of disease elsewhere in the coronary circulation.34

In this longer-term follow-up (mean follow-up, 2.6±0.6 years) of four randomized trials of patients who were treated with either sirolimus-eluting stents or bare metal stents, the mortality rate was low (3–4%), cardiac mortality was even lower (<1.5%), and death was most often due to non-cardiac causes. This dominance of non-cardiac deaths could be due to the low-risk profile of these patients, to the reduction of cardiac events from the treated culprit lesions, to the use of excellent secondary risk factor control, and to the use of concomitant medications such as aspirin, ß-blockers, angiotensin-converting enzyme inhibitors, and statins. Although there were a few differences in early baseline characteristics between patients who survived and patients who died, procedural characteristics and outcome were very similar. There were no significant differences in either the rates or the causes of total mortality, cardiac mortality, or non-cardiac mortality between patients treated with BMSs and those treated with SESs. There was no significant difference between the groups in angiographic restenosis documented before death. The late cardiac deaths are most likely related to progression of disease other than in the culprit lesion, arrhythmia, or progressive left ventricular dysfunction.


   Limitations
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Limitations
Conclusions
 Acknowledgement
 References
 
Determination of the exact cause of death can be difficult. However, the narratives relating to the event were reviewed by both the clinical events committee for each trial and the principal author of this manuscript (D.R.H.). The patients enrolled in these four trials were a select group with low or moderate risk. Whether the results of this analysis are transferable to a wider group of patients and lesions or to other drug-eluting stents remains to be studied; while cardiac mortality is most often reported in the TAXUS series of trials, studies involving the use of both CYPHER and TAXUS stents do not indicate a difference in total, cardiac, or non-cardiac mortality.

Given the size of the respective cohorts, for the observed difference in total mortality to reach statistical significance would have required a sample size of 4621 per group at 80% power with P<0.05; for cardiac mortality, the observed difference in mortality would require a sample size of 211 053 per arm to achieve statistical significance at a similar power and level of significance.

The patients with death of unknown cause were assigned to cardiac mortality. This approach was taken to allow assumption of the worst-case scenario—whether these patients had a cardiac or non-cardiac cause of death cannot be determined. Because of the fairly restrictive definitions of stent thrombosis, it is likely that some of these ‘unknown’ cardiac deaths were, in fact, due to stent thrombosis. The analysis of specific differences in risk factors between patients who died and survivors also suffers from small numbers and post hoc analysis, with the potential for a spurious P-value.That analysis was not, however, the main thrust of this study, which had the aim of assessing the cause of death between the two groups.

The numerically greater non-cardiac deaths in the SES group occurred almost exclusively in C-SIRIUS and RAVEL, which were relatively small trials, but were not seen in the larger SIRIUS trial, suggesting that this imbalance is due to an uncontrolled confounder that was controlled for because of the larger size of the SIRIUS trial. In addition, the difference in non-cardiac deaths in the SES group became apparent only after 180 days, a time course inconsistent with an effect from an implanted drug-eluting stent. Thus, the most likely reason for the higher rate of non-cardiac deaths is the lack of homogeneity in enrolment in the smaller trials that contributed to this integrated analysis.


   Conclusions
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Limitations
 Conclusions
Acknowledgement
 References
 
In this analysis, of 1748 patients entered into four trials, 878 received an SES and 870 a BMS, with a mean follow-up of 2.6±0.6 years. During follow-up, the incidence of all-cause death was low (3–4%) and was most often attributed to a non-cardiac cause. There was no significant difference in the specific cause of death (cardiac vs. non-cardiac) between patients receiving an SES and patients receiving a BMS, and no significant differences in the rates of stent thrombosis or death from stent thrombosis between the two groups of patients.


   Acknowledgement
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Limitations
 Conclusions
 Acknowledgement
References
 
Editing, proofreading, and reference verification were provided by the Section of Scientific Publications, Mayo Clinic.

Conflict of interest: none declared.


   Footnotes
 
{dagger} Nothing in this article implies endorsement of the products of Cordis Corporation. Back


   References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 Limitations
 Conclusions
 Acknowledgement
 References
 

  1. Morice MC, Serruys PW, Sousa JE, Fajadet J, Ban Hayashi E, Perin M, Colombo A, Schuler G, Barragan P, Guagliumi G, Molnar F, Falotico R. RAVEL Study Group. (2002) Randomized study with the sirolimus-coated Bx velocity balloon-expandable stent in the treatment of patients with de novo native coronary artery lesions: a randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 346:1773–1780.[Abstract/Free Full Text]
  2. Fajadet J, Morice MC, Bode C, Barragan P, Serruys PW, Wijns W, Constantini CR, Guermonprez JL, Eltchaninoff H, Blanchard D, Bartorelli A, Laarman GJ, Perin M, Sousa JE, Schuler G, Molnar F, Guagliumi G, Colombo A, Ban Hayashi E, Wulfert E. (2005) Maintenance of long-term clinical benefit with sirolimus-eluting coronary stents: three-year results of the RAVEL trial. Circulation 111:1040–1044.
  3. Moses JW, Leon MB, Popma JJ, Fitzgerald PJ, Holmes DR, O'Shaughnessy C, Caputo RP, Kereiakes DJ, Williams DO, Tierstein PS, Jaeger JL, Kuntz RE. SIRIUS Investigators. (2003) Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 349:1315–1323.[Abstract/Free Full Text]
  4. Holmes DR Jr, Leon MB, Moses JW, Popma JJ, Cutlip D, Fitzgerald PJ, Brown C, Fischell T, Wong SC, Midei M, Snead D, Kuntz RE. (2004) Analysis of 1-year clinical outcomes in the SIRIUS trial: a randomized trial of a sirolimus-eluting stent versus a standard stent in patients at high risk for coronary restenosis. Circulation 109:634–640.
  5. Schofer J, Schluter M, Gershlick AH, Wijns W, Garcia E, Schampaert E, Breithardt G. E-SIRIUS Investigators. (2003) Sirolimus-eluting stents for treatment of patients with long atherosclerotic lesions in small coronary arteries: double-blind, randomised controlled trial (E-SIRIUS). Lancet 362:1093–1099.[CrossRef][ISI][Medline]
  6. Schampaert E, Cohen EA, Schluter M, Reeves F, Traboulsi M, Title LM, Kuntz RE, Popma JJ. C-SIRIUS Investigators. (2004) The Canadian study of the sirolimus-eluting stent in the treatment of patients with long de novo lesions in small native coronary arteries (C-SIRIUS). J Am Coll Cardiol 43:1110–1115.[Abstract/Free Full Text]
  7. Windecker S, Remondino A, Eberli FR, Juni P, Raber L, Wenaweser P, Togni M, Billinger M, Tuller D, Seiler C, Roffi M, Corti R, Sutsch G, Maier W, Luscher T, Hess OM, Egger M, Meier B. (2005) Sirolimus-eluting and paclitaxel-eluting stents for coronary revascularization. N Engl J Med 353:653–662.[Abstract/Free Full Text]
  8. Stone GW, Ellis SG, Cox DA, Hermiller J, O'Shaughnessy C, Mann JT, Turco M, Caputo R, Bergin P, Greenberg J, Popma JJ, Russell ME. TAXUS-IV Investigators. (2004) One-year clinical results with the slow-release, polymer-based, paclitaxel-eluting TAXUS stent: the TAXUS-IV trial. Circulation 109:1942–1947.
  9. Iakovou I, Schmidt T, Bonizzoni E, Ge L, Sangiorgi GM, Stankovic G, Airoldi F, Chieffo A, Montorfano M, Carlino M, Michev I, Corvaja N, Briguori C, Gerckens U, Grube E, Colombo A. (2005) Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 293:2126–2130.[Abstract/Free Full Text]
  10. McFadden EP, Stabile E, Regar E, Cheneau E, Ong AT, Kinnaird T, Suddath WO, Weissman NJ, Torguson R, Kent KM, Pichard AD, Satler LF, Waksman R, Serruys PW. (2004) Late thrombosis in drug-eluting coronary stents after discontinuation of antiplatelet therapy. Lancet 364:1519–1521.[CrossRef][ISI][Medline]
  11. Jeremias A, Sylvia B, Bridges J, Kirtane AJ, Bigelow B, Pinto DS, Ho KK, Cohen DJ, Garcia LA, Cutlip DE, Carrozza JP Jr. (2004) Stent thrombosis after successful sirolimus-eluting stent implantation. Circulation 109:1930–1932.
  12. Chieffo A, Bonizzoni E, Orlic D, Stankovic G, Rogacka R, Airoldi F, Mikhail GW, Montorfano M, Michev I, Carlino M, Colombo A. (2004) Intraprocedural stent thrombosis during implantation of sirolimus-eluting stents. Circulation 109:2732–2736.
  13. Ong AT, McFadden EP, Regar E, de Jaegere PP, van Domburg RT, Serruys PW. (2005) Late angiographic stent thrombosis (LAST) events with drug-eluting stents. J Am Coll Cardiol 45:2088–2092.[Abstract/Free Full Text]
  14. Joner M, Finn AV, Farb A, Mont EK, Kolodgie FD, Ladich E, Kutys R, Skorija K, Gold HK, Virmani R. (2006) Pathology of drug-eluting stents in man: delayed healing and late thrombotic risk. J Am Coll Cardiol 48:193–202.[Abstract/Free Full Text]
  15. Holmes DR Jr, Davis KB, Mock MB, Fisher LD, Gersh BJ, Killip T III, Pettinger M. (1986) The effect of medical and surgical treatment on subsequent sudden cardiac death in patients with coronary artery disease: a report from the Coronary Artery Surgery Study. Circulation 73:1254–1263.
  16. Yusuf S, Zucker D, Peduzzi P, Fisher LD, Takaro T, Kennedy JW, Davis K, Killip T, Passamani E, Norris R, Morris C, Mathur V, Varnauskas E, Chalmers TC. (1994) Effect of coronary artery bypass graft surgery on survival: overview of 10-year results from randomised trials by the Coronary Artery Bypass Graft Surgery Trialists Collaboration. Lancet 344:563–570 (Erratum in: Lancet 1994;344:1446).[CrossRef][ISI][Medline]
  17. Pocock SJ, Henderson RA, Rickards AF, Hampton JR, King SB III, Hamm CW, Puel J, Hueb W, Goy JJ, Rodriguez A. (1995) Meta-analysis of randomised trials comparing coronary angioplasty with bypass surgery. Lancet 346:1184–1189.[CrossRef][ISI][Medline]
  18. Sim I, Gupta M, McDonald K, Bourassa MG, Hlatky MA. (1995) A meta-analysis of randomized trials comparing coronary artery bypass grafting with percutaneous transluminal coronary angioplasty in multivessel coronary artery disease. Am J Cardiol 76:1025–1029.[CrossRef][ISI][Medline]
  19. Hoffman SN, TenBrook JA, Wolf MP, Pauker SG, Salem DN, Wong JB. (2003) A meta-analysis of randomized controlled trials comparing coronary artery bypass graft with percutaneous transluminal coronary angioplasty: one- to eight-year outcomes. J Am Coll Cardiol 41:1293–1304.[Abstract/Free Full Text]
  20. Unger F, Serruys PW, Yacoub MH, Ilsley C, Paulsen PK, Nielsen TT, Eysmann L, Kiemeneij F. (2003) Revascularization in multivessel disease: comparison between two-year outcomes of coronary bypass surgery and stenting. J Thorac Cardiovasc Surg 125:809–820.[Abstract/Free Full Text]
  21. SoS Investigators. (2002) Coronary artery bypass surgery versus percutaneous coronary intervention with stent implantation in patients with multivessel coronary artery disease (the Stent or Surgery trial): a randomised controlled trial. Lancet 360:965–970.[CrossRef][ISI][Medline]
  22. Berger PB, Sketch MH Jr, Califf RM. (2004) Choosing between percutaneous coronary intervention and coronary artery bypass grafting for patients with multivessel disease: what can we learn from the Arterial Revascularization Therapy Study (ARTS)? Circulation 109:1079–1081.
  23. Serruys PW, Unger F, Sousa JE, Jatene A, Bonnier HJ, Schonberger JP, Buller N, Bonser R, van den Brand MJ, van Herwerden LA, Morel MA, van Hout BA. Arterial Revascularization Therapies Study Group. (2001) Comparison of coronary-artery bypass surgery and stenting for the treatment of multivessel disease. N Engl J Med 344:1117–1124.[Abstract/Free Full Text]
  24. Legrand VM, Serruys PW, Unger F, van Hout BA, Vrolix MC, Fransen GM, Nielsen TT, Paulsen PK, Gomes RS, de Queiroz e Melo JM, Neves JP, Lindeboom W, Backx B. Arterial Revascularization Therapy Study (ARTS) Investigators. (2004) Three-year outcome after coronary stenting versus bypass surgery for the treatment of multivessel disease. Circulation 109:1114–1120.
  25. Best PJ and Berger PB. (2004) Can percutaneous coronary interventions reduce death and myocardial infarction in stable and unstable coronary disease? Catheter Cardiovasc Interv 61:528–536.[CrossRef][ISI][Medline]
  26. Al Suwaidi J and Berger PB. (2005) Do stents reduce mortality compared with balloon angioplasty? A critical review of all the evidence. Am Heart J 150:7–10.[CrossRef][ISI][Medline]
  27. Al Suwaidi J, Holmes DR Jr, Salam AM, Lennon R, Berger PB. (2004) Impact of coronary artery stents on mortality and nonfatal myocardial infarction: meta-analysis of randomized trials comparing a strategy of routine stenting with that of balloon angioplasty. Am Heart J 147:815–822.[CrossRef][ISI][Medline]
  28. Hannan EL, Racz MJ, Walford G, Jones RH, Ryan TJ, Bennett E, Culliford AT, Isom OW, Gold JP, Rose EA. (2005) Long-term outcomes of coronary-artery bypass grafting versus stent implantation. N Engl J Med 352:2174–2183.[Abstract/Free Full Text]
  29. Kuchulakanti PK, Chu WW, Torguson R, Ohlmann P, Rha SW, Clavijo LC, Kim SW, Bui A, Gevorkian N, Xue Z, Smith K, Fournadjieva J, Suddath WO, Satler LF, Pichard AD, Kent KM, Waksman R. (2006) Correlates and long-term outcomes of angiographically proven stent thrombosis with sirolimus- and paclitaxel-eluting stents. Circulation 113:1108–1113.
  30. Ong AT, Serruys PW, Aoki J, Hoye A, van Mieghem CA, Rodriguez-Granillo GA, Valgimigli M, Sonnenschein K, Regar E, van der Ent M, de Jaegere PP, McFadden EP, Sianos G, van der Giessen WJ, de Feyter PJ, van Domburg RT. (2005) The unrestricted use of paclitaxel- versus sirolimus-eluting stents for coronary artery disease in an unselected population: one-year results of the Taxus-Stent Evaluated at Rotterdam Cardiology Hospital (T-SEARCH) registry. J Am Coll Cardiol 45:1135–1141.[Abstract/Free Full Text]
  31. Moreno R, Fernandez C, Hernandez R, Alfonso F, Angiolillo DJ, Sabate M, Escaned J, Banuelos C, Fernandez-Oritz A, Macaya C. (2005) Drug-eluting stent thrombosis: results from a pooled analysis including 10 randomized studies. J Am Coll Cardiol 45:954–959.[Abstract/Free Full Text]
  32. Urban P, Gershlick AH, Guagliumi G, Guyon P, Lotan C, Schofer J, Seth A, Sousa JE, Wijns W, Berge C, Deme M, Stoll HP. e-Cypher Investigators. (2006) Safety of coronary sirolimus-eluting stents in daily clinical practice: one-year follow-up of the e-Cypher registry. Circulation 113:1434–1441.
  33. Iakovou I, Schmidt T, Bonizzoni E, Ge L, Sangiorgi GM, Stankovic G, Airoldi F, Chieffo A, Montorfano M, Carlino M, Michev I, Corvaja N, Briguori C, Gerckens U, Grube E, Colombo A. (2005) Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 293:2126–2130.[Abstract/Free Full Text]
  34. Cutlip DE, Chhabra AG, Baim DS, Chauhan MS, Marulkar S, Massaro J, Bakhai A, Cohen DJ, Kuntz RE, Ho KK. (2004) Beyond restenosis: five-year clinical outcomes from second-generation coronary stent trials. Circulation 110:1226–1230.

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