Advertisement






Click here for more guidelines.
CME Topic Collections Past Issues Search Current Issue Home
     

J Am Coll Cardiol, 2008; 52:1041-1048, doi:10.1016/j.jacc.2008.06.030
© 2008 by the American College of Cardiology Foundation
This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (7)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shishehbor, M. H.
Right arrow Articles by Ellis, S. G.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Shishehbor, M. H.
Right arrow Articles by Ellis, S. G.
Related Collections
Right arrowRelated Article

CLINICAL RESEARCH: INTERVENTIONAL CARDIOLOGY

Long-Term Impact of Drug-Eluting Stents Versus Bare-Metal Stents on All-Cause Mortality

Mehdi H. Shishehbor, DO, MPH, Sachin S. Goel, MD, Samir R. Kapadia, MD, Deepak L. Bhatt, MD, Peter Kelly, MD, Russell E. Raymond, DO, John M. Galla, MD, Sorin J. Brener, MD, Patrick L. Whitlow, MD and Stephen G. Ellis, MD*

Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio

Manuscript received February 14, 2008; revised manuscript received June 2, 2008, accepted June 3, 2008.

* Reprint requests and correspondence: Dr. Stephen G. Ellis, Department of Cardiovascular Medicine, Desk F25, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195 (Email: elliss{at}ccf.org).


    Abstract
 Top
 Abstract
 Methods
 Results
 Discussion
 Conclusions
 References
 
Objectives: Our purpose was to examine the incidence of all-cause mortality among drug-eluting stents (DES) and bare-metal stents (BMS) while adjusting for many confounding factors generally not considered in prior studies.

Background: DES use in the U.S. declined by up to 50% in recent years, primarily due to concerns about late stent thrombosis and possibly increased mortality. However, recent data suggest that DES are as safe as BMS and may actually be associated with a lower incidence of myocardial infarction and mortality.

Methods: All patients undergoing percutaneous coronary intervention with a DES or BMS alone from March 1, 2003, to June 30, 2007, at a tertiary care center were assessed. Multivariable Cox proportional hazards modeling was performed for overall and propensity-matched patients. Socioeconomic status was calculated using U.S. Census 2000 data. The primary end point was all-cause mortality.

Results: There were a total of 832 deaths over a 4.5-year interval among 8,032 patients. Of these, 6,053 received a DES and 1,983 patients had a BMS. All-cause mortality was significantly lower in unadjusted and adjusted Cox proportional models with DES (hazard ratio: 0.62, 95% confidence interval: 0.53 to 0.73; p < 0.001). Similarly, in the propensity-matched group, DES remained associated with lower mortality compared with BMS (adjusted hazard ratio: 0.54, 95% confidence interval: 0.45 to 0.66; p < 0.001).

Conclusions: DES were associated with lower mortality in this "real-world" setting. However, despite multiple adjustments, potential confounding may still play a role.

Key Words: drug-eluting stents • bare-metal stents • all-cause mortality • propensity

Abbreviations and Acronyms
  BMS = bare-metal stent(s)
  CI = confidence interval
  DES = drug-eluting stent(s)
  HR = hazard ratio
  MI = myocardial infarction
  PCI = percutaneous coronary intervention
  SES = socioeconomic status


Unlike earlier studies that raised concern about drug-eluting stents (DES) (1), a recent meta-analysis of randomized trials has shown that DES, in addition to reducing restenosis and, hence, target vessel revascularization, may also reduce the rate of myocardial infarction (MI) (2). Additionally, others have shown lower mortality with DES compared with bare-metal stents (BMS) up to 2 years (3–5). While these data are reassuring, there remains concern over whether selection bias may have led to a lower event rate in the DES group. Specifically, since the published reports in late 2004 and 2005, patients with extensive comorbidities or terminal illnesses such as malignancy, medical noncompliance, and those with a low socioeconomic status (SES) typically receive BMS because of concern regarding abrupt withdraw of dual antiplatelet therapy. This policy regarding stent implantation based on aforementioned variables may explain the lower event rate with DES noted in recent studies (3,4). Additionally, maximum duration of follow-up in the most recent studies has been 2 years (3,4). Therefore, we sought to examine the rate of long-term all-cause mortality among patients who received DES versus BMS in a "real-world" setting, while adjusting for SES, malignancy, depression, anemia, renal function, and other confounding variables.


    Methods
 Top
 Abstract
 Methods
 Results
 Discussion
 Conclusions
 References
 
Study population.   The study population was obtained from the prospective percutaneous coronary intervention (PCI) patient registry at Cleveland Clinic. All patients from March 1, 2003, to June 30, 2007, who underwent an index PCI procedure with a BMS or DES alone were included. Baseline characteristics, cardiac history, risk factors, medications, and angiographic and procedural data were prospectively obtained and recorded by experienced research coordinators. The primary end point was all-cause mortality, which was assessed by querying the Social Security Death Index. The institutional review board waived requirements for informed consent for the institutional PCI registry.

Additional confounding variables.   Blood studies are routinely obtained on all patients before PCI including white blood cell count, serum hemoglobin, hematocrit, and creatinine. Using electronic records, levels of the above variables were merged with patients undergoing PCI. The closest blood work before and within 3 weeks of procedural date was selected. Similarly, using ICD-9 coding and procedural date, all malignancies and the presence of depression were identified within 1 year before the index procedure.

Socioeconomic score.   Individual socioeconomic level data were not available; therefore, each patient's home address was geocoded and matched to the U.S. 2000 census data. Census block level data, a geographical unit containing approximately 1,000 residents, was used to calculate a composite SES score for each patient as described previously (6). Previous work in population-based cohorts demonstrated the value of this score as an independent predictor of cardiovascular risk and an excellent surrogate for individual level SES data (6–8).

Statistical analysis.   Continuous variables are presented as mean ± standard deviation. Differences in baseline and angiographic characteristics were compared using the Wilcoxon rank sum test for continuous variables and the chi-square test for categorical variables. We used Cox proportional hazards modeling to examine the association between the use of BMS and DES and all-cause mortality while accounting for the differences in baseline demographic features, angiographic variables, SES, cancer, depression, blood levels of hematocrit, creatinine, white blood cell count, and other confounders (Table 1).


View this table:
[in this window]
[in a new window]

 
Table 1 Baseline Characteristics of Nonpropensity-Matched Patients According to Stent Type
 
In order to address potential selection bias that may have occurred in mid-2005 due to concerns about late stent thrombosis, we conducted our analysis for each year starting in 2003, separately. Additionally, in order to minimize the impact of confounding, we employed the technique of propensity analysis and matching. We used a nonparsimonious logistic regression model to generate a propensity score for the type of stent used (BMS vs. DES) using most variables listed in Table 1, except stent length and procedural success; however, lesion length was included. We then matched each subject from the BMS group to an individual that had PCI with DES using the derived propensity score. Matches were made if the propensity score between the 2 patients from different groups was identical by 5 digits. If this could not be achieved, then matching was made by 4, 3, 2, or 1 digit. Once this threshold was reached, the BMS-treated individual was excluded. Subsequently, we performed Cox proportional hazards modeling where we incorporated all baseline characteristics shown in Table 2, in addition to the propensity score, for the propensity-matched patients.


View this table:
[in this window]
[in a new window]

 
Table 2 Baseline Characteristics for Propensity-Matched Patients According to Stent Type
 
The proportional hazards assumption was tested by calculating weighted Schoenfeld residuals and by inspecting the hazard ratio (HR) against time plots (9). Model overfitting was tested using bootstrapping, which for all models turned out to be trivial; the reported c-statistics are "optimism corrected," meaning that they have been adjusted for any overfitting. This is done by applying the model obtained from the bootstrap sample to the original data. Average optimism is then computed by subtracting accuracy index obtained from 100 bootstrap resamplings minus the index computed on the original sample (9). The overfitting-corrected estimate is then calculated by subtracting the average optimism from the final model fit's apparent accuracy (9). Model calibration was assessed by plots of observed versus predicted values derived from 100 bootstrap resamplings. Colinearity was assured by calculation of variance inflation factors. A number of subgroup analyses were also performed for pre-specified groups of interest. Pre-specified interaction testing between DES and age, diabetes, malignancy, serum creatinine, SES, and white blood cell count was also performed.

All statistical analyses were performed using SAS software (version 9.1, SAS Institute, Cary, North Carolina) and S-plus 7.0 (Insightful, Inc., Seattle, Washington). All tests were 2-tailed; a p value of <0.05 was considered significant.


    Results
 Top
 Abstract
 Methods
 Results
 Discussion
 Conclusions
 References
 
Baseline characteristics.   Overall, there were 11,181 PCIs performed between March 2003 and June 2007. After excluding patients that did not receive a stent and those that underwent repeat procedures, 8,036 met our study criteria. Of these, 6,053 patients underwent PCI with DES and 1,983 patients with BMS (53% were stainless steel and 47% were cobalt/chromium stents). Patients who received BMS had higher prevalence of comorbidities such as malignancy (Table 1). However, patients undergoing intervention on chronic total occlusions, in-stent restenosis, longer lesions, and multivessel disease were more likely to receive DES (Table 1).

Outcome for overall population.   A total of 832 deaths occurred. The rate of death was significantly lower in the DES group compared with that in the BMS group during the 4.5 years of follow-up (8% vs. 17%, p < 0.001) (Fig. 1A). Similarly, DES use was associated with lower mortality for each consecutive year (Table 3). In a multivariable Cox proportional hazard analysis after adjusting for all variables shown in Table 1, DES use was associated with a 38% relative risk reduction for all-cause mortality (Table 3). Similarly, this association remained significant for each consecutive year from 2003 to 2007 except for 2004 (Table 3). Additional analysis that divided the whole population into those that received a stent from March 2003 to May 2005 and those from June 2005 to June 2007 also showed similar results with lower mortality in the DES group (Table 4). Similar results were also obtained by subgroup analysis for stent diameter <2.5 mm (DES vs. BMS, adjusted HR: 0.52, 95% confidence interval [CI]: 0.32 to 0.84, p = 0.008), stent diameter <3.5 mm (DES vs. BMS, adjusted HR: 0.65, 95% CI: 0.55 to 0.78, p < 0.001), and stent diameter >3.5 mm (DES vs. BMS, adjusted HR: 0.42, 95% CI: 0.26 to 0.66, p < 0.001).


Figure 1
View larger version (18K):
[in this window]
[in a new window]
[Download PPT slide]
 
Figure 1 Kaplan-Meier Curves for Overall Nonpropensity-Matched Population

Dotted lines represent 95% confidence intervals.

 

View this table:
[in this window]
[in a new window]

 
Table 3 Adjusted Cox Proportional HR for Nonpropensity- and Propensity-Matched Patients
 

View this table:
[in this window]
[in a new window]

 
Table 4 Adjusted Cox Proportional HR for Nonpropensity- and Propensity-Matched Patients According to Pre-Selected Subgroups
 
Propensity analyses.   Of the 1,983 patients who received BMS, 1,801 (91%) matched with an individual who received a DES (c-statistic for overall group = 0.79). Baseline characteristics of the propensity-matched group are shown in Table 2. In general, both groups were well matched for over 50 confounding variables. The only 2 variables that were statistically different among the 2 groups were stent length and lesion length, both of which favored BMS (Table 2).

A total of 472 deaths occurred in the propensity-matched population. In unadjusted analysis, DES use was significantly associated with lower all-cause mortality (Fig. 2). In the multivariable Cox proportional hazard model that adjusted for all baseline characteristics in addition to the propensity score, DES use remained significantly associated with lower mortality (Table 3).


Figure 2
View larger version (18K):
[in this window]
[in a new window]
[Download PPT slide]
 
Figure 2 Kaplan-Meier Curves for Overall Propensity-Matched Population

Dotted lines represent 95% confidence intervals.

 
A series of subgroup analyses were also performed; in all cases both in the overall nonpropensity-matched and the propensity-matched patients, DES was significantly associated with lower mortality (Table 4). Of the interactions tested, only the interaction between DES and pre-treatment white blood cell count had a trend toward significance (p = 0.08).

Multivariable predictors of all-cause mortality.   Of the over 50 variables included in the saturated Cox proportional hazard model, only age, DES, body mass index, insulin-dependent diabetes, peripheral vascular disease, left ventricular ejection fraction, intervention to the right coronary artery, New York Heart Association functional class IV, chronic obstructive lung disease, history of stroke or transient ischemic attack, statin therapy, heart rate, socioeconomic score, serum creatinine, white blood cell count, and presence of malignancy were predictive of all-cause mortality. Of the variables mentioned above, only age (chi-square: 91.89, p < 0.001), serum creatinine (chi-square: 72.12, p < 0.001), chronic obstructive lung disease (chi-square: 62.36, p < 0.001), cancer (chi-square: 50.73, p < 0.001), hematocrit (chi-square: 45.69, p < 0.001), and left ventricular ejection fraction (chi-square: 45.09, p < 0.001) had higher predictive value than intervention with DES (chi-square: 43.66, p < 0.001).


    Discussion
 Top
 Abstract
 Methods
 Results
 Discussion
 Conclusions
 References
 
In patients undergoing PCI with DES or BMS in the "real-world" setting, the use of DES appears to be associated with lower all-cause mortality. This result was persistent despite multiple adjustments, including propensity analysis, stratified analysis by procedure year, and by subgroup analysis. Additionally, adjustment for SES, presence of cancer, anemia, or renal insufficiency did not change this result.

In October of 2004, McFadden et al. (10) reported 4 cases of late stent thrombosis after DES placement. Subsequently, a series of studies raised concerns regarding DES and the risk of late stent thrombosis (11–15). Collectively, this led to a significant reduction in DES use. These concerns resulted in a significant decline in DES use from 80% to 90% in 2004 to 40% to 50% in 2006 in most institutions. However, despite these earlier concerns, recent studies indicate that DES may actually result in lower mortality or MI (2,3). Tu et al. (3) evaluated 3,751 matched patients who received DES or BMS from 2003 to 2005 and showed a reduction in target vessel revascularization and death up to 3 years. Similarly, Mauri et al. (5) evaluated 17,000 patients treated with PCI in the non-U.S. government hospitals in Massachusetts between April 1, 2003, and September 30, 2005, for a 2-year follow-up and showed a significantly lower mortality with DES use. Stettler et al. (2) conducted a pooled head-to-head analysis of randomized DES trials and showed a reduction in MI with sirolimus-eluting stents. Our study adds to the above findings by considering the presence of cancer, anemia, renal insufficiency, depression, and an aggregate SES.

The exact mechanism for the apparent decrease in mortality seen with DES is unknown. While reduction in restenosis-related death and MI may play a substantial role, it does not completely explain the lower incidence of death seen with DES use (16–18). Additionally, it seems that patients with complex lesions benefit the most from DES, and these individuals were typically excluded from randomized control trials (19). Patients undergoing stenting with DES receive longer duration of therapy with dual antiplatelet agents, aspirin, and clopidogrel. This could partially explain the lower mortality seen in these patients, as dual antiplatelet therapy in the setting of acute coronary syndromes and PCI has been associated with lower events (20–26). An alternative reason for the significant mortality difference with recent studies compared with that seen in randomized trials is the duration of follow-up. To our knowledge, the current study has one of the longest follow-ups to date.

While our results indicate that DES use was associated with lower mortality, unmeasured confounding factors may still play an important role. Our study provides long-term follow-up with adequate statistical power. Multiple adjustments were performed, including for the presence of malignancy, depression, anemia, renal insufficiency, aggregate SES, propensity analysis, and individualized year-by-year evaluation, and in all instances, DES was associated with better outcome.

Study limitations.   The current study has limitations in that it is an observational study and is prone to biases related to unmeasured factors. However, interventional registry data are prospectively collected by professional staff and contain detailed clinical and angiographic data. Additional information such as the presence of malignancy, depression, and anemia, serum levels of white blood cell count and creatinine, and SES was also obtained. In all cases, results consistently favored DES. Another limitation is that the study is from a single center and may not be easily generalized to all patients. For example, about one-third of our patients had prior coronary bypass graft surgery; therefore, our cohort has higher risk features compared with that of other studies. Also, before 2005, only the first 1,000 consecutive patients were followed prospectively for events such as stent thrombosis, revascularization, or MI. Therefore, we did not have complete data on these important end points, and, hence, they were not included in this analysis. However, all-cause mortality is likely the most unbiased and clinically relevant outcome (27). Additionally, the association between DES and stent thrombosis has been well investigated (2,3,28,29). Also, data on dual antiplatelet therapy was not available. Lastly, because of the observational nature of the present study, we still remain cautious in suggesting that DES use actually results in lower mortality.


    Conclusions
 Top
 Abstract
 Methods
 Results
 Discussion
 Conclusions
 References
 
In this analysis, DES use was associated with lower mortality in long-term analysis and despite multiple adjustments. Given the significance of this outcome, long-term randomized clinical trials that include patients with complex coronary lesions should examine this association. In the meantime, this study and the preponderance of the evidence support the notion that the overall risk of stent thrombosis with DES does not translate into higher mortality in these patients.


    Acknowledgments
 
The authors are grateful to Dr. Anil Jain (Managing Director, eResearch, Information Technology, staff physician, Medicine Institute, Cleveland Clinic) for assistance with data on laboratory values, malignancy, and depression. The authors also would like to thank Ms. Kathryn Brock (Editorial Service Manager, Cardiovascular Medicine, Cleveland Clinic) for her editorial assistance.


    Footnotes
 
Dr. Shishehbor is supported, in part, by Case Western Reserve University/Cleveland Clinic CTSA (1KL2RR024990). Dr. Bhatt has received research grants (directly to the institution) from Bristol-Myers Squibb, Eisai, Ethicon, Heartscape, Sanofi-Aventis, The Medicines Company; honoraria (donated to nonprofits for >2 years): AstraZeneca, Bristol-Myers Squibb, Centocor, Daiichi-Sankyo, Eisai, Eli Lilly, GlaxoSmithKline, Millennium, Paringenix, PDL, Sanofi-Aventis, Schering-Plough, The Medicines Company, tns Healthcare; Speakers' Bureau (>2 years ago): Bristol-Myers Squibb, Sanofi-Aventis, The Medicines Company; consultant/advisory board (any honoraria donated to nonprofits): Astellas, AstraZeneca, Bristol-Myers Squibb, Cardax, Centocor, Cogentus, Daiichi-Sankyo, Eisai, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, McNeil, Medtronic, Millennium, Molecular Insights, Otsuka, Paringenix, PDL, Philips, Portola, Sanofi-Aventis, Schering-Plough, Scios, The Medicines Company, tns Healthcare, Vertex; expert testimony regarding clopidogrel (the compensation was donated to a nonprofit organization); Cleveland Clinic Coordinating Center currently receives or has received research funding from: Abraxis, Alexion Pharma, AstraZeneca, Atherogenics, Aventis, Biosense Webster, Biosite, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardionet, Centocor, Converge Medical Inc., Cordis, Dr. Reddy's, Edwards Lifesciences, Esperion, GE Medical, Genentech, Gilford, GlaxoSmithKline, Guidant, Johnson & Johnson, Kensey-Nash, Eli Lilly, Medtronic, Merck, Mytogen, Novartis, Novo Nordisk, Orphan Therapeutics, Procter & Gamble Pharma, Pfizer, Roche, Sankyo, Sanofi-Aventis, Schering-Plough, Scios, St. Jude Medical, Takeda, The Medicines Company, VasoGenix, and Viacor. Dr. Whitlow has received research grant support from Abbott Vascular, Boston Scientific, and Evalve Inc. and has received consulting fees from Medlogics and Icon International Systems Inc. Dr. Ellis has received consulting fees from Boston Scientific, Cordis, and Abbott Vascular.


    References
 Top
 Abstract
 Methods
 Results
 Discussion
 Conclusions
 References
 
1. Lagerqvist B, James SK, Stenestrand U, Lindback J, Nilsson T, Wallentin L. Long-term outcomes with drug-eluting stents versus bare-metal stents in Sweden N Engl J Med 2007;356:1009-1019.[Abstract/Free Full Text]

2. Stettler C, Wandel S, Allemann S, et al. Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis Lancet 2007;370:937-948.[CrossRef][Web of Science][Medline]

3. Tu JV, Bowen J, Chiu M, et al. Effectiveness and safety of drug-eluting stents in Ontario N Engl J Med 2007;357:1393-1402.[Abstract/Free Full Text]

4. Jensen LO, Maeng M, Kaltoft A, et al. Stent thrombosis, myocardial infarction, and death after drug-eluting and bare-metal stent coronary interventions J Am Coll Cardiol 2007;50:463-470.[Abstract/Free Full Text]

5. Mauri L, Silverstein T, Lovett A, Resnic F, Normand S. Long-term clinical outcomes following drug-eluting and bare metal stenting in Massachusetts. Presented at: 2007 American Heart Association Scientific Sessions; November 4–7, 2007: Orlando, FL.

6. Diez Roux AV, Merkin SS, Arnett D, et al. Neighborhood of residence and incidence of coronary heart disease N Engl J Med 2001;345:99-106.[Abstract/Free Full Text]

7. Krieger N, Chen JT, Waterman PD, Soobader MJ, Subramanian SV, Carson R. Geocoding and monitoring of US socioeconomic inequalities in mortality and cancer incidence: does the choice of area-based measure and geographic level matter?: the Public Health Disparities Geocoding Project Am J Epidemiol 2002;156:471-482.[Abstract/Free Full Text]

8. Shishehbor MH, Litaker D, Pothier CE, Lauer MS. Association of socioeconomic status with functional capacity, heart rate recovery, and all-cause mortality JAMA 2006;295:784-792.[Abstract/Free Full Text]

9. Harrell FE. Regression Modeling Strategies With Applications to Linear Models, Logistic Regression, and Survival AnalysisNew York, NY: Springer-Verlag; 2001.

10. 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.[CrossRef][Web of Science][Medline]

11. Bavry AA, Kumbhani DJ, Helton TJ, Borek PP, Mood GR, Bhatt DL. Late thrombosis of drug-eluting stents: a meta-analysis of randomized clinical trials Am J Med 2006;119:1056-1061.[CrossRef][Web of Science][Medline]

12. Ong AT, Hoye A, Aoki J, et al. Thirty-day incidence and six-month clinical outcome of thrombotic stent occlusion after bare-metal, sirolimus, or paclitaxel stent implantation J Am Coll Cardiol 2005;45:947-953.[Abstract/Free Full Text]

13. Moreno R, Fernandez C, Hernandez R, et al. Drug-eluting stent thrombosis: results from a pooled analysis including 10 randomized studies J Am Coll Cardiol 2005;45:954-959.[Abstract/Free Full Text]

14. Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents JAMA 2005;293:2126-2130.[Abstract/Free Full Text]

15. Fujii K, Carlier SG, Mintz GS, et al. Stent underexpansion and residual reference segment stenosis are related to stent thrombosis after sirolimus-eluting stent implantation: an intravascular ultrasound study J Am Coll Cardiol 2005;45:995-998.[Abstract/Free Full Text]

16. Chen MS, John JM, Chew DP, Lee DS, Ellis SG, Bhatt DL. Bare metal stent restenosis is not a benign clinical entity Am Heart J 2006;151:1260-1264.[CrossRef][Web of Science][Medline]

17. Stone GW, Ellis SG, Colombo A, et al. Offsetting impact of thrombosis and restenosis on the occurrence of death and myocardial infarction after paclitaxel-eluting and bare metal stent implantation Circulation 2007;115:2842-2847.[Abstract/Free Full Text]

18. Doyle B, Rihal CS, O'Sullivan CJ, et al. Outcomes of stent thrombosis and restenosis during extended follow-up of patients treated with bare-metal coronary stents Circulation 2007;116:2391-2398.[Abstract/Free Full Text]

19. Abbott JD, Voss MR, Nakamura M, et al. Unrestricted use of drug-eluting stents compared with bare-metal stents in routine clinical practice: findings from the National Heart, Lung, and Blood Institute Dynamic Registry J Am Coll Cardiol 2007;50:2029-2036.[Abstract/Free Full Text]

20. Chen ZM, Jiang LX, Chen YP, et al. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial Lancet 2005;366:1607-1621.[CrossRef][Web of Science][Medline]

21. Sabatine MS, Cannon CP, Gibson CM, et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation N Engl J Med 2005;352:1179-1189.[Abstract/Free Full Text]

22. Steinhubl SR, Berger PB, Mann 3rd JT, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial JAMA 2002;288:2411-2420.[Abstract/Free Full Text]

23. Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation N Engl J Med 2001;345:494-502.[Abstract/Free Full Text]

24. Eisenstein EL, Anstrom KJ, Kong DF, et al. Clopidogrel use and long-term clinical outcomes after drug-eluting stent implantation JAMA 2007;297:159-168.[Abstract/Free Full Text]

25. Bhatt DL, Flather, MD, Hacke W, et al. Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial J Am Coll Cardiol 2007;49:1982-1988.[Abstract/Free Full Text]

26. Bhatt DL, Fox KA, Hacke W, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events N Engl J Med 2006;354:1706-1717.[Abstract/Free Full Text]

27. Lauer MS, Blackstone EH, Young JB, Topol EJ. Cause of death in clinical research: time for a reassessment? J Am Coll Cardiol 1999;34:618-620.[Free Full Text]

28. Maisel WH. Unanswered questions—drug-eluting stents and the risk of late thrombosis N Engl J Med 2007;356:981-984.[Free Full Text]

29. Shuchman M. Debating the risks of drug-eluting stents N Engl J Med 2007;356:325-328.[Free Full Text]


Related Article

Inside This Issue of JACC
J. Am. Coll. Cardiol. 2008 52: A34. [Full Text] [PDF]



This article has been cited by other articles:


Home page
J Am Coll CardiolHome page
S. R. Dixon, C. L. Grines, and W. W. O'Neill
The year in interventional cardiology.
J. Am. Coll. Cardiol., June 2, 2009; 53(22): 2080 - 2097.
[Full Text] [PDF]


Home page
J Am Coll CardiolHome page
P. S. Douglas, J. M. Brennan, K. J. Anstrom, A. Sedrakyan, E. L. Eisenstein, G. Haque, D. Dai, D. F. Kong, B. Hammill, L. Curtis, et al.
Clinical Effectiveness of Coronary Stents in Elderly Persons: Results From 262,700 Medicare Patients in the American College of Cardiology-National Cardiovascular Data Registry
J. Am. Coll. Cardiol., May 5, 2009; 53(18): 1629 - 1641.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
A. N. DeMaria, O. Ben-Yehuda, J. J. Bax, G. K. Feld, B. H. Greenberg, W. Y.W. Lew, J. A.C. Lima, A. S. Maisel, S. M. Narayan, D. J. Sahn, et al.
Highlights of the Year in JACC 2008.
J. Am. Coll. Cardiol., January 27, 2009; 53(4): 373 - 398.
[Full Text] [PDF]


This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (7)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shishehbor, M. H.
Right arrow Articles by Ellis, S. G.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Shishehbor, M. H.
Right arrow Articles by Ellis, S. G.
Related Collections
Right arrowRelated Article

 
  CME Topic Collections Past Issues Search Current Issue Home

Advertisement