International Journal of Cardiology 172 (2014) e203–e206
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Head-to-head comparison of everolimus-eluting stents versus zotarolimus-eluting stents in patients undergoing percutaneous coronary intervention: A meta-analysis Xin-lin Zhang, Ran Li, Han Wu, Qin-hua Chen, Guan-nan Li, Jun Xie, Biao Xu ⁎ Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China
a r t i c l e
i n f o
Article history: Received 5 October 2013 Received in revised form 23 December 2013 Accepted 26 December 2013 Available online 8 January 2014 Keywords: Meta-analysis Head-to-head Percutaneous coronary intervention Everolimus-eluting stent Zotarolimus-eluting stent
The outstanding performance of drug-eluting stents in reducing the incidence of restenosis has been well documented as compared with bare-metal stents in recent studies. However, concerns have been raised on the long-term safety of the first-generation drug-eluting stents, particularly a higher rate of late stent thrombosis has been reported in some studies [1]. Therefore, the second-generation drug-eluting stents—everolimus-eluting stents (EES) and Endeavor zotarolimuseluting stents (ZES)—have been developed to improve the safety while maintaining the efficiency. To date, EES and Endeavor ZES have been evaluated in numerous clinical trials [2]. However, the relative safety and efficiency of EES and Endeavor ZES remain unclear. Although head-to-head comparative observational studies have been conducted in recent years, no result from randomized controlled trial has been published. Therefore, we performed a meta-analysis of observational studies (unadjusted and adjusted separately) to compare the efficacy and safety of EES with Endeavor ZES in patients undergoing percutaneous coronary intervention. A systematic search of studies published before June 15, 2013, was conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases. The search terms used were everolimus-eluting stent and zotarolimus-eluting stent. In addition, we ⁎ Corresponding author at: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Zhongshan Road 321, Nanjing 210008, China. Tel.: +86 25 831 052 05; fax: +86 25 833 0 80 59. E-mail address: [email protected] (B. Xu). 0167-5273/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.12.153
checked the reference lists of all the identified records for potential relevant citations. Two reviewers (X.L.Z. and R.L.) independently assessed study eligibility by first screening the identified titles and abstracts, articles with potential inclusion were then reviewed in full text. Disagreements were resolved by consensus. To be selected for the meta-analysis, studies had to make head-to-head comparisons of everolimus-eluting stents (EES, Xience V, Abbott Vascular, Santa Clara, California; or Promus, Boston Scientific, Natick, Massachusetts) with zotarolimus-eluting stents (ZES, Endeavor, Medtronic Vascular, Santa Rosa, California) in patients undergoing percutaneous coronary intervention. All studies reported outcomes of interest with a follow-up of at least 6 months. No language restriction was imposed. The primary outcome of interest was target vessel revascularization (TVR). Other clinical endpoints were cardiac death, all-cause death, myocardial infarction, stent thrombosis, target lesion revascularization (TLR), and major adverse cardiac events (MACE). Meta-analyses were performed separately for unadjusted studies and adjusted studies (propensity matching or covariate adjustment). In each study, we retrieved or calculated relative risks (RRs) and their corresponding 95% confidence intervals (CIs) to assess the selected outcomes. All meta-analyses were performed with the DerSimonian and Laird random-effects model. Cochrane's Q statistic (significant at p b 0.10) and the I2 statistic were conducted to investigate the heterogeneity across studies. Publication bias was evaluated with the Begg and Egger tests. In addition, we performed sensitivity analyses by removing an individual study each time to test the robustness of our findings. All probability values were 2-tailed and p ≤ 0.05 was considered statistically significant. Statistical analyses were performed with the STATA version 11.0 (STATA Corporation, College Station, TX, USA) software. Of the 932 potentially relevant articles initially retrieved, 10 studies with full-text articles met the inclusion criteria and were included in the meta-analysis, enrolling a total of 14,018 patients [3–12]. Baseline characteristics and lengths of follow-up of the selected studies are shown in Table 1. The mean age of patients ranged from 60 to 68 years with the majority of patients being male. The durations of follow-up were 12 months in all studies except one [10], whose follow-up length was 24 months. The recommended duration of clopidogrel therapy was commonly 12 months, while one study did not specify the duration [10]. In unadjusted observational studies, TVR was needed in 3.4% of patients treated with EES and 6.3% of patients treated with Endeavor
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Table 1 Characteristics of the studies included in the meta-analysis. Trial/First Author
a
2008 2010 2010 2011 2011 2012 2012 2012 2012 2013
Patient profile
e
ISR Unselected Unselected Angina Bifurcation AMIj Unselected Unselected Unselected STEMIm
No. of patients
Age, y
E
Z
E
23 98 2219 61 117 1701 1643 388
23 100 2549 50 107 1608 1643 370
61 60 66 65 64 63
190 412
197 519
Z ± ± ± ±
9 1 12 11
± 12
65 ± 11 66 ± 11 61 ± 12
60 61 67 68 63 64
± ± ± ±
13 1 12 9
± 13
65 ± 11 67 ± 12 62 ± 12
DM: diabetes mellitus. MI: myocardial infarction. c ACS: acute coronary syndrome. d DAPT: dual-antiplatelet therapy. e ISR: in-stent restenosis. f MACE: major adverse cardiac event. g ESTROF-A-2: Estudio Español Sobre Trombosis de Stents Farmacoactivos de Segunda Generacion-2. h ST: stent thrombosis. i KAMIR: Korea Acute Myocardial Infarction Registry. j AMI: acute myocardial infarction. k TLR: target lesion revascularization. l PROENCY: PROmus ENdeavor Cypher Registry. m STEMI: ST-segment elevation myocardial infarction. b
DMa %
Men %
Hypertension %
Hyperlipidemia %
Prior MIb %
ACSc %
E
Z
E
Z
E
Z
E
Z
E
Z
100 44 76 89 84 73 65 77
83 67 76 86 76 72 71 75
22 45 36 31 40 33 66 29
35 34 32 20 26 29 67 35
70 87 59 74 64 49
61 81 60 64 51 50
87 70 54 61 54 15
70 63 52 54 45 15
47 19 8 20 4
50 19 14 20 5
76
76
67
69
28
25
66 75
68 73
37 13
37 13
81 40
77 39
85 21
84 20
39 10
29 10
E
DAPTd, mo
Fu, mo
MACEf MACE STh MACE MACE MACE TLRk, death
12 12 12 12 12 12 12
13 12 12 12 12 12 24 12
12 12
12 12
Z
52 27 69
30 13 75
69 100
71 100
52 100
Primary endpoint
48 100
MACE MACE, etc. MACE
X. Zhang et al. / International Journal of Cardiology 172 (2014) e203–e206
Toutouzas et al. Collet et al. ESTROFA-2g CASTOR-Bifurcation Herrador et al. KAMIRi Hannan et al. PROENCYl STEMI: ST-segment elevation myocardial infarction. Shammas et al. Velders et al.
Year
X. Zhang et al. / International Journal of Cardiology 172 (2014) e203–e206
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ZES. EES was associated with a significant reduction in rates of TVR as compared with Endeavor ZES (RR: 0.54; 95% CI: 0.38–0.77) (Fig. 1). Meanwhile, EES treated patients had significant lower rates of TLR
Fig. 2. Pooled relative risks (RRs) and 95% confidence intervals (CIs) of endpoints in patients treated with everolimus-eluting stents (EES) versus those treated with zotarolimus-eluting stents (ZES) in propensity matching or adjusted observational studies. The relative risks with 95% confidence intervals (CIs) were pooled with a random effect model. CI: confidence interval; EES: everolimus-eluting stent; MACE: major adverse cardiac events; RR: relative risk; TLR: target lesion revascularization; TVR: target vessel revascularization; ZES: zotarolimus-eluting stent.
(RR: 0.35; 95% CI: 0.24–0.52), death (RR: 0.67; 95% CI: 0.54–0.84), cardiac death (RR: 0.68; 95% CI: 0.52–0.87), stent thrombosis (RR: 0.35; 95% CI: 0.14–0.86), and MACE (RR: 0.51; 95% CI: 0.39–0.67). A trend toward lower rate of myocardial infarction was also observed in EES-treated patients (RR: 0.73; 95% CI: 0.50–1.07). Five studies with full-text articles and 3 abstracts from international conferences [13–15] reported adjusted results of outcomes of interest comparing EES with Endeavor ZES. Analyses of these 8 studies (15,011 patients) showed statistically similar results with those from the unadjusted studies (Fig. 2). No significant heterogeneity was found among included studies for all the endpoints except stent thrombosis in unadjusted studies (I2 = 55.9). Our present study is the first head-to-head meta-analysis of adjusted and unadjusted observational studies to date evaluating the safety and efficacy of EES versus Endeavor ZES. The fact that results of unadjusted studies were consistent with adjusted studies strengthened our findings. In our study, EES was safer and more efficacious than Endeavor ZES, as evidenced by reductions in rates of TVR, TLR, mortality, stent thrombosis, MACE, and a trend toward reducing rate of myocardial infarction in EES-treated patients. Our findings are strengthened by the results of the most comprehensive network meta-analysis [16], which showed that EES was associated with a lower risk of TVR, TLR, stent thrombosis, and a trend toward lower risk of death compared with Endeavor ZES. To the best of our knowledge, no clinical data from head-to-head randomized controlled trials comparing EES with Endeavor ZES has been published yet and may not be expected in the future. Thus, the present meta-analysis may remain the sole evidence on the relative performance of EES and Endeavor ZES. This work was supported by grants from the National Natural Science Foundation of China (research grants 81070195, 81270281 and 81200148), and Jiangsu Key Laboratory for Molecular Medicine of Nanjing University, and Jiangsu Provincial Special Program of Medical Science (BL2012014), and the State Key Laboratory of Pharmaceutical Biotechnology (KF-GN-200901), and the Peak of Six Personnel in Jiangsu Province (2013-WSN-008), and Funds for Distinguished Young Scientists in Nanjing (Xie Jun). The corresponding author had full access
Fig. 1. Forest plot with RRs and 95% CIs for TVR (A), TLR (B), death (C), cardiac death (D), stent thrombosis (E), myocardial infarction (F) and MACE (G) associated with everolimuseluting stents (EES) versus zotarolimus-eluting stents (ZES) pooled from unadjusted observational studies. The relative risks with 95% confidence intervals (CIs) were pooled with a random effect model. The size of each square is proportional to the weight of the individual studies. CI: confidence interval; EES: everolimus-eluting stent; MACE: major adverse cardiac events; RR: relative risk; ZES: zotarolimus-eluting stent.
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X. Zhang et al. / International Journal of Cardiology 172 (2014) e203–e206
to all the data in the study and had final responsibility for the decision to submit for publication. No authors have any condition that may represent a potential conflict of interest. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
References [1] Pfisterer M, Brunner-La Rocca HP, Buser PT, et al. Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting versus bare-metal stents. J Am Coll Cardiol 2006;48:2584–91. [2] Stone GW, Midei M, Newman W, et al. Comparison of an everolimus-eluting stent and a paclitaxel-eluting stent in patients with coronary artery disease: a randomized trial. J Am Med Assoc 2008;299:1903–13. [3] Toutouzas K, Patsa C, Tsiamis E, et al. Everolimus- and zotarolimus-eluting stents for bare metal stent in-stent restenosis treatment: a prospective study. J Interv Cardiol 2008;21:388–94. [4] Collet CA, Costa Jr JR, Feres F, et al. Everolimus-eluting stent versus zotarolimus-eluting stent in the real word clinical practice. Rev Bras Cardiol Invasiva 2010;18:400–6. [5] de la Torre Hernandez JM, Alfonso F, Gimeno F, et al. Thrombosis of secondgeneration drug-eluting stents in real practice results from the multicenter Spanish registry ESTROFA-2 (Estudio Espanol Sobre Trombosis de Stents Farmacoactivos de Segunda Generacion-2). JACC Cardiovasc Interv 2010;3:911–9. [6] Herrador JA, Fernandez JC, Guzman M, Aragon V. Comparison of zotarolimus- versus everolimus-eluting stents in the treatment of coronary bifurcation lesions. Catheter Cardiovasc Interv 2011;78:1086–92.
[7] Sgueglia GA, Burzotta F, Trani C, et al. Comparative assessment of mammalian target of rapamycin inhibitor-eluting stents in the treatment of coronary artery bifurcation lesions: the CASTOR-Bifurcation registry. Catheter Cardiovasc Interv 2011;77:503–9. [8] Chen KY, Rha SW, Wang L, et al. Unrestricted use of 2 new-generation drug-eluting stents in patients with acute myocardial infarction: a propensity score-matched analysis. JACC Cardiovasc Interv 2012;5:936–45. [9] Damman P, Abdel-Wahab M, Mollmann H, et al. Comparison of twelve-month outcomes after percutanous coronary intervention with everolimus-eluting versus zotarolimus-eluting or sirolimus-eluting stents from the PROENCY (PROmus ENdeavor CYpher) registry. J Invasive Cardiol 2012;24:495–502. [10] Hannan EL, Zhong Y, Wu C, et al. Everolimus-eluting stents and zotarolimus-eluting stents for percutaneous coronary interventions: two-year outcomes in New York State. Catheter Cardiovasc Interv 2013;81:1097–105. [11] Shammas NW, Shammas GA, Nader E, et al. Outcomes of patients treated with the everolimus-eluting stent versus the zotarolimus eluting stent in a consecutive cohort of patients at a tertiary medical center. Vasc Health Risk Manag 2012;8:205–11. [12] Velders MA, Boden H, van der Hoeven BL, et al. Long-term outcome of secondgeneration everolimus-eluting stents and Endeavor zotarolimus-eluting stents in a prospective registry of ST-elevation myocardial infarction patients. EuroIntervention 2013;8:1199–206. [13] Hong SJ. Comparison of angiographic and clinical outcomes among patients with sirolimus-, paclitaxel-, zotarolimus-, and everolimus-eluting stent implantation in small coronary target vessels. EuroIntervention 2012;8:N66. [14] Olivecrona GKH, Kedhi E, Omerovic E, James S, Smith JG, Lagerqvist B. Comparison of drug-eluting stents in real-life clinical practice in Sweden: insights from the SCAAR Register. J Am Coll Cardiol 2010;56:B60. [15] Lee JM, Youn TJ, Oh IY, et al. Comparison of unrestricted use of resolute zotarolimuseluting and everolimus-eluting stents: outcomes in a real world setting of coronary intervention in Koreans. J Am Coll Cardiol 2012;59:E413. [16] Bangalore S, Kumar S, Fusaro M, et al. Short- and long-term outcomes with drugeluting and bare-metal coronary stents: a mixed-treatment comparison analysis of 117 762 patient-years of follow-up from randomized trials. Circulation 2012;125: 2873–91.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Head-to-head comparison of everolimus-eluting stents versus zotarolimus-eluting stents in patients undergoing percutaneous coronary intervention: A meta-analysis Xin-lin Zhang, Ran Li, Han Wu, Qin-hua Chen, Guan-nan Li, Jun Xie, Biao Xu ⁎ Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China
a r t i c l e
i n f o
Article history: Received 5 October 2013 Received in revised form 23 December 2013 Accepted 26 December 2013 Available online 8 January 2014 Keywords: Meta-analysis Head-to-head Percutaneous coronary intervention Everolimus-eluting stent Zotarolimus-eluting stent
The outstanding performance of drug-eluting stents in reducing the incidence of restenosis has been well documented as compared with bare-metal stents in recent studies. However, concerns have been raised on the long-term safety of the first-generation drug-eluting stents, particularly a higher rate of late stent thrombosis has been reported in some studies [1]. Therefore, the second-generation drug-eluting stents—everolimus-eluting stents (EES) and Endeavor zotarolimuseluting stents (ZES)—have been developed to improve the safety while maintaining the efficiency. To date, EES and Endeavor ZES have been evaluated in numerous clinical trials [2]. However, the relative safety and efficiency of EES and Endeavor ZES remain unclear. Although head-to-head comparative observational studies have been conducted in recent years, no result from randomized controlled trial has been published. Therefore, we performed a meta-analysis of observational studies (unadjusted and adjusted separately) to compare the efficacy and safety of EES with Endeavor ZES in patients undergoing percutaneous coronary intervention. A systematic search of studies published before June 15, 2013, was conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases. The search terms used were everolimus-eluting stent and zotarolimus-eluting stent. In addition, we ⁎ Corresponding author at: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Zhongshan Road 321, Nanjing 210008, China. Tel.: +86 25 831 052 05; fax: +86 25 833 0 80 59. E-mail address: [email protected] (B. Xu). 0167-5273/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.12.153
checked the reference lists of all the identified records for potential relevant citations. Two reviewers (X.L.Z. and R.L.) independently assessed study eligibility by first screening the identified titles and abstracts, articles with potential inclusion were then reviewed in full text. Disagreements were resolved by consensus. To be selected for the meta-analysis, studies had to make head-to-head comparisons of everolimus-eluting stents (EES, Xience V, Abbott Vascular, Santa Clara, California; or Promus, Boston Scientific, Natick, Massachusetts) with zotarolimus-eluting stents (ZES, Endeavor, Medtronic Vascular, Santa Rosa, California) in patients undergoing percutaneous coronary intervention. All studies reported outcomes of interest with a follow-up of at least 6 months. No language restriction was imposed. The primary outcome of interest was target vessel revascularization (TVR). Other clinical endpoints were cardiac death, all-cause death, myocardial infarction, stent thrombosis, target lesion revascularization (TLR), and major adverse cardiac events (MACE). Meta-analyses were performed separately for unadjusted studies and adjusted studies (propensity matching or covariate adjustment). In each study, we retrieved or calculated relative risks (RRs) and their corresponding 95% confidence intervals (CIs) to assess the selected outcomes. All meta-analyses were performed with the DerSimonian and Laird random-effects model. Cochrane's Q statistic (significant at p b 0.10) and the I2 statistic were conducted to investigate the heterogeneity across studies. Publication bias was evaluated with the Begg and Egger tests. In addition, we performed sensitivity analyses by removing an individual study each time to test the robustness of our findings. All probability values were 2-tailed and p ≤ 0.05 was considered statistically significant. Statistical analyses were performed with the STATA version 11.0 (STATA Corporation, College Station, TX, USA) software. Of the 932 potentially relevant articles initially retrieved, 10 studies with full-text articles met the inclusion criteria and were included in the meta-analysis, enrolling a total of 14,018 patients [3–12]. Baseline characteristics and lengths of follow-up of the selected studies are shown in Table 1. The mean age of patients ranged from 60 to 68 years with the majority of patients being male. The durations of follow-up were 12 months in all studies except one [10], whose follow-up length was 24 months. The recommended duration of clopidogrel therapy was commonly 12 months, while one study did not specify the duration [10]. In unadjusted observational studies, TVR was needed in 3.4% of patients treated with EES and 6.3% of patients treated with Endeavor
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Table 1 Characteristics of the studies included in the meta-analysis. Trial/First Author
a
2008 2010 2010 2011 2011 2012 2012 2012 2012 2013
Patient profile
e
ISR Unselected Unselected Angina Bifurcation AMIj Unselected Unselected Unselected STEMIm
No. of patients
Age, y
E
Z
E
23 98 2219 61 117 1701 1643 388
23 100 2549 50 107 1608 1643 370
61 60 66 65 64 63
190 412
197 519
Z ± ± ± ±
9 1 12 11
± 12
65 ± 11 66 ± 11 61 ± 12
60 61 67 68 63 64
± ± ± ±
13 1 12 9
± 13
65 ± 11 67 ± 12 62 ± 12
DM: diabetes mellitus. MI: myocardial infarction. c ACS: acute coronary syndrome. d DAPT: dual-antiplatelet therapy. e ISR: in-stent restenosis. f MACE: major adverse cardiac event. g ESTROF-A-2: Estudio Español Sobre Trombosis de Stents Farmacoactivos de Segunda Generacion-2. h ST: stent thrombosis. i KAMIR: Korea Acute Myocardial Infarction Registry. j AMI: acute myocardial infarction. k TLR: target lesion revascularization. l PROENCY: PROmus ENdeavor Cypher Registry. m STEMI: ST-segment elevation myocardial infarction. b
DMa %
Men %
Hypertension %
Hyperlipidemia %
Prior MIb %
ACSc %
E
Z
E
Z
E
Z
E
Z
E
Z
100 44 76 89 84 73 65 77
83 67 76 86 76 72 71 75
22 45 36 31 40 33 66 29
35 34 32 20 26 29 67 35
70 87 59 74 64 49
61 81 60 64 51 50
87 70 54 61 54 15
70 63 52 54 45 15
47 19 8 20 4
50 19 14 20 5
76
76
67
69
28
25
66 75
68 73
37 13
37 13
81 40
77 39
85 21
84 20
39 10
29 10
E
DAPTd, mo
Fu, mo
MACEf MACE STh MACE MACE MACE TLRk, death
12 12 12 12 12 12 12
13 12 12 12 12 12 24 12
12 12
12 12
Z
52 27 69
30 13 75
69 100
71 100
52 100
Primary endpoint
48 100
MACE MACE, etc. MACE
X. Zhang et al. / International Journal of Cardiology 172 (2014) e203–e206
Toutouzas et al. Collet et al. ESTROFA-2g CASTOR-Bifurcation Herrador et al. KAMIRi Hannan et al. PROENCYl STEMI: ST-segment elevation myocardial infarction. Shammas et al. Velders et al.
Year
X. Zhang et al. / International Journal of Cardiology 172 (2014) e203–e206
e205
ZES. EES was associated with a significant reduction in rates of TVR as compared with Endeavor ZES (RR: 0.54; 95% CI: 0.38–0.77) (Fig. 1). Meanwhile, EES treated patients had significant lower rates of TLR
Fig. 2. Pooled relative risks (RRs) and 95% confidence intervals (CIs) of endpoints in patients treated with everolimus-eluting stents (EES) versus those treated with zotarolimus-eluting stents (ZES) in propensity matching or adjusted observational studies. The relative risks with 95% confidence intervals (CIs) were pooled with a random effect model. CI: confidence interval; EES: everolimus-eluting stent; MACE: major adverse cardiac events; RR: relative risk; TLR: target lesion revascularization; TVR: target vessel revascularization; ZES: zotarolimus-eluting stent.
(RR: 0.35; 95% CI: 0.24–0.52), death (RR: 0.67; 95% CI: 0.54–0.84), cardiac death (RR: 0.68; 95% CI: 0.52–0.87), stent thrombosis (RR: 0.35; 95% CI: 0.14–0.86), and MACE (RR: 0.51; 95% CI: 0.39–0.67). A trend toward lower rate of myocardial infarction was also observed in EES-treated patients (RR: 0.73; 95% CI: 0.50–1.07). Five studies with full-text articles and 3 abstracts from international conferences [13–15] reported adjusted results of outcomes of interest comparing EES with Endeavor ZES. Analyses of these 8 studies (15,011 patients) showed statistically similar results with those from the unadjusted studies (Fig. 2). No significant heterogeneity was found among included studies for all the endpoints except stent thrombosis in unadjusted studies (I2 = 55.9). Our present study is the first head-to-head meta-analysis of adjusted and unadjusted observational studies to date evaluating the safety and efficacy of EES versus Endeavor ZES. The fact that results of unadjusted studies were consistent with adjusted studies strengthened our findings. In our study, EES was safer and more efficacious than Endeavor ZES, as evidenced by reductions in rates of TVR, TLR, mortality, stent thrombosis, MACE, and a trend toward reducing rate of myocardial infarction in EES-treated patients. Our findings are strengthened by the results of the most comprehensive network meta-analysis [16], which showed that EES was associated with a lower risk of TVR, TLR, stent thrombosis, and a trend toward lower risk of death compared with Endeavor ZES. To the best of our knowledge, no clinical data from head-to-head randomized controlled trials comparing EES with Endeavor ZES has been published yet and may not be expected in the future. Thus, the present meta-analysis may remain the sole evidence on the relative performance of EES and Endeavor ZES. This work was supported by grants from the National Natural Science Foundation of China (research grants 81070195, 81270281 and 81200148), and Jiangsu Key Laboratory for Molecular Medicine of Nanjing University, and Jiangsu Provincial Special Program of Medical Science (BL2012014), and the State Key Laboratory of Pharmaceutical Biotechnology (KF-GN-200901), and the Peak of Six Personnel in Jiangsu Province (2013-WSN-008), and Funds for Distinguished Young Scientists in Nanjing (Xie Jun). The corresponding author had full access
Fig. 1. Forest plot with RRs and 95% CIs for TVR (A), TLR (B), death (C), cardiac death (D), stent thrombosis (E), myocardial infarction (F) and MACE (G) associated with everolimuseluting stents (EES) versus zotarolimus-eluting stents (ZES) pooled from unadjusted observational studies. The relative risks with 95% confidence intervals (CIs) were pooled with a random effect model. The size of each square is proportional to the weight of the individual studies. CI: confidence interval; EES: everolimus-eluting stent; MACE: major adverse cardiac events; RR: relative risk; ZES: zotarolimus-eluting stent.
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X. Zhang et al. / International Journal of Cardiology 172 (2014) e203–e206
to all the data in the study and had final responsibility for the decision to submit for publication. No authors have any condition that may represent a potential conflict of interest. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
References [1] Pfisterer M, Brunner-La Rocca HP, Buser PT, et al. Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting versus bare-metal stents. J Am Coll Cardiol 2006;48:2584–91. [2] Stone GW, Midei M, Newman W, et al. Comparison of an everolimus-eluting stent and a paclitaxel-eluting stent in patients with coronary artery disease: a randomized trial. J Am Med Assoc 2008;299:1903–13. [3] Toutouzas K, Patsa C, Tsiamis E, et al. Everolimus- and zotarolimus-eluting stents for bare metal stent in-stent restenosis treatment: a prospective study. J Interv Cardiol 2008;21:388–94. [4] Collet CA, Costa Jr JR, Feres F, et al. Everolimus-eluting stent versus zotarolimus-eluting stent in the real word clinical practice. Rev Bras Cardiol Invasiva 2010;18:400–6. [5] de la Torre Hernandez JM, Alfonso F, Gimeno F, et al. Thrombosis of secondgeneration drug-eluting stents in real practice results from the multicenter Spanish registry ESTROFA-2 (Estudio Espanol Sobre Trombosis de Stents Farmacoactivos de Segunda Generacion-2). JACC Cardiovasc Interv 2010;3:911–9. [6] Herrador JA, Fernandez JC, Guzman M, Aragon V. Comparison of zotarolimus- versus everolimus-eluting stents in the treatment of coronary bifurcation lesions. Catheter Cardiovasc Interv 2011;78:1086–92.
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