Original research

259

Long-term effect of second-generation drug-eluting stents for coronary artery disease, everolimus-eluting versus zotarolimus-eluting stents: a meta-analysis Li Qi-Hua, Zhang Qi, Zhi Yu, Li Xiao-Long, Ji Hai-Gang, Yin Jian-Feng and Sun Yi Background Compared with the zotarolimus-eluting stent (ZES), the everolimus-eluting stent (EES) has reduced the risk of stent restenosis and thrombosis as found in a number of randomized-controlled trials (RCTs). However, the benefits have been variable. Materials and methods We evaluate the long-term effect of EES and ZES on the risk of stent thrombosis and target lesion revascularization in patients receiving PCI. We identified RCTs by a systematic search of MEDLINE, EMBASE, and Cochrane Database. Results Five RCTs (9853 patients) were included. Overall, EES significantly reduced the risk of target lesion revascularization [odds ratio (OR), 0.77; 95% confidence interval (CI), 0.62–0.95; P = 0.01] compared with ZES therapy. However, there was no difference in the risk of target vessel revascularization (OR, 0.93; 95% CI, 0.78–1.10; P = 0.38) and definite/probable stent thrombosis (OR, 0.83; 95% CI, 0.56–1.25; P = 0.37) between the two groups. Furthermore, the risk of mortality (OR, 1.04; 95% CI,

Introduction Compared with the bare-metal stents (BMS), the sirolimus-eluting stent and paclitaxel-eluting stent have consistently been shown to significantly reduce the rates of in-stent late loss, angiographic restenosis, and target vessel revascularization (TVR) [1]. However, concerns were driven by the higher rates of late clinical events owing to stent thrombosis (ST) in patients receiving firstgeneration DES [2]. Another concern was the observation of delayed restenosis with DES [2]. The second-generation DES, everolimus-eluting stent (EES), and zotarolimus-eluting stent (ZES) incorporate a thin-strut cobalt or platinum chromium stent platform, new antiproliferative agents, and a biocompatible polymer [1]. Evidence from a comprehensive network metaanalysis showed that compared with BMS and firstgeneration DES, EES was associated with better stent endothelialization [3], which is strongly linked to a reduced rate of late and very late ST [3–5]. However, the TWENTE trial showed that 2-year rates of definite or probable ST were comparable (1.2 vs. 1.4%, P = 0.63) between the EES and ZES groups [6]. Moreover, the 4-year rates of late ST (0.2 vs. 0.6%, P = 0.10) and very late ST (0.7 vs. 0.9%, P = 0.81) were also similar between 0954-6928 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

0.84–1.27; P = 0.73), myocardial infarction (OR, 0.95; 95% CI, 0.74–1.23; P = 0.70), and major adverse cardiac event (OR, 0.96; 95% CI, 0.84–1.10; P = 0.53) was similar between the two groups. Conclusion The new-generation Resolute-ZES and EES have a similar long-term safety and efficacy profile. Coron Artery Dis 26:259–265 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Coronary Artery Disease 2015, 26:259–265 Keywords: everolimus-eluting stent, major adverse cardiovascular event, stent restenosis, stent thrombosis, zotarolimus-eluting stent Department of Cardiology, Changzhou TCM Hospital, Changzhou, China Correspondence to Qi Zhang, MD, No. 25 Heping Road, Tianning District, Changzhou, China Tel: + 86 0519 89896898; fax: + 86 0519 89896898; e-mail: [email protected] Received 13 September 2014 Revised 30 December 2014 Accepted 4 January 2015

the two groups in the RESOLUTE study [7]. Meanwhile, TVR continues to occur in more than 5% of patients treated with new-generation DES at 1 year, suggesting that long-term follow-up is needed. Although several studies have been carried out in recent years, no head-to-head meta-analysis of randomized trials with long-term follow-up has been published. With recently accumulating evidence, the aim of the present study was to evaluate the long-term risk of ST and TVR by carrying out a meta-analysis of randomized-controlled trials (RCTs) of EES versus ZES therapy for patients undergoing PCI.

Materials and methods Data sources and searches strategy

We searched MEDLINE (source, PubMed, 2000 to August 2014), EMBASE (2000 to August 2014), and the Cochrane Database (through August 2014) using the terms ‘everolimus-eluting stent’, ‘zotarolimus-eluting stent’, ‘drug-eluting stent’, ‘coronary artery disease’, ‘target vessel revascularization’, and ‘stent thrombosis’. Manual reference checking of the bibliographies of all relevant articles was performed. No restrictions were applied. DOI: 10.1097/MCA.0000000000000222

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260 Coronary Artery Disease 2015, Vol 26 No 3

Study selection

Results

We first performed an initial screening of titles and/or abstracts. The second evaluation was based on full-text reviews. Trials were considered eligible if they fulfilled the following criteria: (a) the study was RCT; (b) the study was carried out in patients undergoing PCI and followed up at least 12 months; (c) the intervention consisted of EES and Resolute-ZES therapy; (d) the primary end-point was ST and target lesion revascularization (TLR); and (e) the secondary endpoints were death, myocardial infarction (MI), and major adverse cardiac event (MACE).

Search results

Data extraction

Data extraction was performed using a standardized datacollection form. The details extracted were patients’ characteristics, dual-antiplatelet therapy duration, followup time, study quality, and the incidence of ST and MACE. The definition of ST was classified into three categories of definite, probable, and possible in the academic research consortium (ARC) definition. The ARC consensus also recommends temporal categories of early (0–30 days), late (31 days–1 year), and very late (>1 year) ST. MACE is defined as the composite endpoints of cardiac death, myocardial infarction, and target vessel revascularization.

Quality assessment

We initially identified 261 potentially relevant articles. Sixty-two articles were considered to be of interest and were retrieved for full-text reviews. Fifty-seven articles were excluded, and finally, five studies were included in our meta-analysis. A flow chart showing the study selection is presented (Fig. 1). Study characteristics

Five published trials [6,7,12–14] with a total of 9853 patients were included in our study. The number of patients in each study ranged from 650 to 3755 and the duration of follow-up varied from 12 to 48 months (mean duration, 21.6 months). The participants’ ages ranged from 18 to 85 years (mean age, 66.7 years old). Most were Fig. 1

187 records identified through database searching

44 additional records identified through other sources

201 records after duplicates removed

201 records screened

The PRISMA (Preferred Reporting Items for Systemic Reviews and Meta-Analyses) statement [8] was followed. The principal components used for quality assessment were generation of random sequence, allocation concealment, blinding of outcome assessment, loss of followup of outcome measure, and selective outcome reporting.

Data synthesis and analysis

Results were analyzed quantitatively by Review Manager 5.0 (The Cochrane Collaboration, Oxford, UK) using the fixed-effects and random-effects (DerSimonian and Laird random-effects) models [9]. Heterogeneity was examined by the I2 statistic and the χ2-test, and a value of I2 more than 50% was considered a high level of heterogeneity [10,11]. For outcomes with significant heterogeneity (I2 > 50%), the random-effects model is reported in the text and figures; for all others, the fixedeffects models are reported. We calculated the pooled odds ratio (OR) for dichotomous outcomes with a 95% confidence interval (CI) on an intent-to-treat basis. Statistical significance was set at the 0.05 level for both the I2 test for heterogeneity and the Z-test for OR.

139 records excluded as irrelevant or review articles

57 excluded including: 37 not random 8 follow-up < 1 year 6 subgroups analysis 62 full-text articles assessed for eligibility

2 survive rate only 1 Endeavor ZES as control

5 studies included in qualitative synthesis

5 studies included in quantitative synthesis (meta-analysis) Flow chart of study selection. Flow chart shows the literature search for randomized-controlled trials of everolimus-eluting stent versus zotarolimus-eluting stent (ZES) therapy for coronary artery disease.

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EES reduced rate of TVR Qi-Hua et al. 261

Characteristics of patients in the everolimus-eluting stent and zotarolimus-eluting stent groups from five randomizedcontrolled trials

Table 1

RCTs (references)

Year

FU (months)

Number of patients

Age (years)

Male (%)

HT (%)

DM (%)

ACS (%)

DAPT (months)

ZES type

TWENTE [6] ISAR-LEFT-MAIN 2 [12] RESOLUTE [7] HOST-ASSURE [13] DUTCH PEERS [14]

2013 2013 2014 2014 2014

24 12 48 12 12

1391 650 2246 3755 1811

64.5/63.9 70.2/69.4 64.2/64.4 63.1/63.5 65.0/64.0

72.6/72.5 77.3/72.8 77.2/76.7 69.8/65.6 73.0/73.0

55.8/55.4 69.9/68.2 71.3/71.1 68.2/68.1 53.0/55.0

20.6/22.7 28.5/28.4 23.4/23.5 31.8/32.0 17.0/18.0

51.1/52.0 32.8/38.3 18.9/19.4a 65.5/65.6 59.0/58.0

12 12 6 12 12

ZES-R ZES-R ZES-R ZES-R ZES-R

ACS, acute coronary syndrome; DAPT, recommended dual-antiplatelet therapy duration; DM, diabetes mellitus; EES, everolimus-eluting stent; FU, follow-up; HT, hypertension; NR, not reported; RCT, randomized-controlled trial; ZES-R, zotarolimus-eluting stent Resolute. a Unstable angina.

men (mean, 73.1%); 66.2% had hypertension, 23.7% had diabetes mellitus, and 47.2% presented with acute coronary syndrome. More than 6 months of dual-antiplatelet therapy was recommended for all trials (Table 1). Methodological quality assessment

All trials randomized the participants, and reported details of the randomization process used [6,7,12–14]. All studies used methods of concealed treatment allocation adequately, except one [7]. All trials blinded outcome assessors to treatment allocation, except one [14] and there was no risk of attrition bias and reporting bias in any of the studies (Fig. 2). Stent thrombosis, target lesion revascularization, and target vessel revascularization Stent thrombosis

Five trials [6,7,12–14] provided long-term follow-up data on ARC definite and/or probable ST. There were 5552 patients in the EES group, and ST occurred in 47 patients (0.85%). There were 4301 patients in the ZES group, and ST occurred in 50 patients (1.16%). EES did not significantly decrease the rate of ARC definite/ probable ST (OR, 0.83; 95% CI, 0.56–1.25; P = 0.37; I2 = 0%) compared with the ZES therapy (Fig. 3). Furthermore, the rates of early (OR, 0.58; 95% CI, 0.26–1.32; P = 0.20; I2 = 45%), late (OR, 0.38; 95% CI, 0.13–1.14; P = 0.08; I2 = 0%), and very late (OR, 1.17; 95% CI, 0.39–3.48; P = 0.78; I2 = 0%) definite ST were similar between the two groups (Fig. 4). Target lesion revascularization

TLR was shown in all five studies [6,7,12–14]. There were 5552 patients in the EES group, and 178 patients had TLR (3.21%). There were 4301 patients in the Resolute-ZES group, and 209 had TLR (4.85%). Overall, EES significantly reduced the rate of TLR compared with ZES treatment (OR, 0.77; 95% CI, 0.62–0.95; P = 0.01; I2 = 17%) (Fig. 5). Target vessel revascularization

TVR was shown in five trials [6,7,12–14], with a total of 9853 patients. There were 5552 patients in the EES group, and 299 patients had TVR (5.38%). There were 4301 patients in the ZES group, and 283 patients had

TVR (6.57%). Overall, the rate of TVR was similar between the two groups (OR, 0.93; 95% CI, 0.78–1.10; P = 0.04; I2 = 38%) (Fig. 6). Mortality, MI and major adverse cardiac event Mortality

All-cause mortality data were reported in five trials [6,7, 12–14]. A total of 216 patients died in the EES group (3.89%) and 184 patients died in the ZES group (4.27%). There was no significant difference in the risk of death between the two groups (OR, 1.04; 95% CI, 0.84–1.27; P = 0.73; I2 = 17%) (Fig. 7). Meanwhile, the risk of cardiac death was also similar between the two groups (OR, 0.95; 95% CI, 0.73–1.25; P = 0.73; I2 = 17%). MI and major adverse cardiac event

MI was reported in four studies [6,7,12,13]. There were 4647 patients in the EES group, and MI occurred in 132 patients (2.84%). There were 3395 patients in the ZES group, and 123 patients had MI (3.62%). The rate of MI was similar (OR, 0.95; 95% CI, 0.74–1.23; P = 0.70; I2 = 0%) between the two groups. Furthermore, EES was also associated with a trend toward reducing the risk of MACE (OR, 0.89; 95% CI, 0.79–1.00; P = 0.06; I2 = 55.0%) compared with ZES therapy (Fig. 8).

Discussion Our study represents the first head-to-head meta-analysis of randomized studies with long-term follow-up to date evaluating the safety and efficacy of EES versus ZES therapy. Compared with ZES, EES has a similar safety and efficacy in long-term follow-up, as evidenced by reductions in rates of TVR and a trend toward reducing the rate of MACE. Furthermore, rates of ST, mortality, and MI were comparable between the two groups. The long-term safety and efficacy of these two new drugeluting stents are clinically equivalent. To the best of our knowledge, this study incorporates all data available reported to date. Several studies have found that compared with BMS, DES was associated with a markedly higher risk of very late ST (1.9 vs. 0.5%), which was associated with delayed stent re-endothelialization [15]. The long-term 4-year follow-up of the RESOLUTE study [7], which included 2292 patients, has found that rates of very late ST were

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262 Coronary Artery Disease 2015, Vol 26 No 3

Previous studies have found that compared with Endeavor-ZES, EES was associated with a significantly lower risk of TVR (12.2 vs. 6.2%; P < 0.05) [16]. Combining two randomized trials (ISAR-TEST 2 and ISAR-TEST 5), Tada et al. [17] found that the incidence of TLR at 2 years was 12.0% in the Resolute-ZES group and 16.0% in the Endeavor-ZES (HR, 0.72; 95% CI, 0.51–1.00; P = 0.052). Compared with Endeavor-ZES, Resolute-ZES showed overall superior antirestenotic efficacy. The Resolute-ZES is similar to the EndeavorZES, but the drug release is sustained over a longer period (180 vs. 14 days) [1]. In line with previous trials, our study showed that the rate of TVR was similar between the EES and the Resolute-ZES groups.

Blinding of outcome assessment (detection bias)

Incomplete outcome data (attrition bias)

Selective reporting (reporting bias)

Other bias

+

+

+

Allocation concealment (selection bias)

+

Random sequence generation (selection bias)

Blinding of participants and personnel (performance bias)

Fig. 2

DUTCH PEERS [14]

+

+

HOST-ASSURE [13]

+

+

+

+

ISAR-LEFT-MAIN 2 [12]

+

+

+

+

RESOLUTE [7]

+



+

TWENTE [6]

+

+

+

Methodological assessment of included studies on the basis of the PRISMA statement. PRISMA, Preferred Reporting Items for Systemic Reviews and Meta-Analyses.

Patients with unprotected left main coronary artery lesions are at a high risk for ischemic events. The greater need for repeat revascularizations remains the major contributor toward the difference in clinical efficacy between different DES treatments. At 1 year, the ISARLEFT-MAIN 2 study [12] showed that the incidence of TLR was 11.7% in the ZES group and 9.4% in the EES group, which was markedly lower (1.2%) in patients without left main lesion [13]. However, angiographic data showed that the incidence of binary restenosis was similar between the EES and the ZES groups (RR, 1.28; 95% CI, 0.86–1.92; P = 0.24) [12]. Thus, for patients with left main lesion, both the ZES and the EES are associated with an excellent procedural success rate and showed similar safety and efficacy.

similar with EES and Resolute-ZES (0.4 vs. 0.4%; P = 1.00). Similarly, on longer follow-up (12–48 months), we also found that very late ST was not significantly different between the two groups (0.38 vs. 0.32%; P = 0.78).

Recent case series have raised the issue of longitudinal stent deformation (LSD) [18], which was associated with stent restenosis and ST. Of 5010 stents analyzed, the HOST-ASSURE study [13] found that LSD occurred in 0.2 and 0% in the EES and ZES groups, respectively (P = 0.104). In the DUTCH PEERS study [14], LSD was observed only in patients assigned to treatment with EES

+

+

+

+

+

+

+

+

+

+

+

+

+

Fig. 3

EES Study or subgroup DUTCH PEERS [14] HOST-ASSURE [13] ISAR-LEFT-MAIN 2 [12] RESOLUTE [7] TWENTE [6]

Events

ZES Total

8 905 9 2503 2 326 18 1124 10 694

Events

Odds ratio

Odds ratio

Total Weight (%) M-H, Fixed, 95% CI

5 906 8 1252 3 324 26 1122 8 697

9.5 20.4 5.7 49.2 15.1

1.61 (0.52–4.93) 0.56 (0.22–1.46) 0.66 (0.11–3.98) 0.69 (0.37–1.26) 1.26 (0.49–3.21)

Total (95% CI) 5552 4301 47 50 Total events Heterogeneity: 2 = 3.18, d.f. = 4 (P = 0.53); I 2 = 0% Test for overall effect: Z = 0.89 (P = 0.37)

100.0

0.83 (0.56–1.25)

0.01

M-H, fixed, 95% CI

0.1 Favours EES

1

10

100

Favours ZES

Definite/probable ST meta-analysis of six trials. Fixed-effect model (I2 = 0.0%; P = 0.30). CI, confidence interval; EES, everolimus-eluting stent; ST, stent thrombosis; ZES, zotarolimus-eluting stent.

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EES reduced rate of TVR Qi-Hua et al. 263

Fig. 4

EES Study or subgroup Events Total Early definite stent thrombosis 694 0 TWENTE [6] 1 1124 RESOLUTE [7] DUTCH PEERS [14] 905 4 HOST-ASSURE [13] 5 2503 5226 Subtotal (95% CI) 10 Total events

ZES Odds ratio Events Total Weight (%) M-H, fixed, 95% CI 1 697 9 1122 2 906 2 1252 3977 14

4.6 0.33 (0.01–8.22) 27.7 0.11 (0.01–0.87) 6.1 2.01 (0.37–10.98) 8.2 1.25 (0.24–6.46) 46.7 0.58 (0.26–1.32)

Year

Odds ratio M-H, fixed, 95% CI

2013 2014 2014 2014

Heterogeneity: 2 = 5.48, d.f. = 3 (P = 0.14); I2 = 45% Test for overall effect: Z = 1.29 (P = 0.20) Late definite stent thrombosis 0 3 697 694 TWENTE [6] 1 1252 HOST-ASSURE [13] 2 2503 5 1122 RESOLUTE [7] 2 1124 1 906 DUTCH PEERS [14] 0 905 Subtotal (95% CI) 5226 3977 10 Total events 4 Heterogeneity: 2 = 1.05, d.f. = 3 (P = 0.79); I2 = 0% Test for overall effect: Z = 1.73 (P = 0.08) Very late definite stent thrombosis 2 TWENTE [6] 694 2 697 RESOLUTE [7] 5 1124 4 1122 Subtotal (95% CI) 1818 1819 Total events 7 6 Heterogeneity: 2 = 0.03, d.f. = 1 (P = 0.86); I2 = 0% Test for overall effect: Z = 0.28 (P = 0.78)

10.8 0.14 (0.01–2.77) 2013 4.1 1.00 (0.09–11.04) 2014 15.4 0.40 (0.08–2.06) 2014 4.6 0.33 (0.01–8.19) 2014 34.9 0.38 (0.13–1.14)

6.1 12.3 18.4

Total (95% CI) 12270 9773 100.0 30 Total events 21 Heterogeneity: 2 = 8.20, d.f. = 9 (P = 0.51); I2 = 0% Test for overall effect: Z = 1.70 (P = 0.09) Test for subgroup differences: 2 = 2.07 , d.f. = 2 (P = 0.35), I2 = 3.4%

1.00 (0.14–7.15) 2013 1.25 (0.33–4.66) 2014 1.17 (0.39–3.48)

0.62 (0.36–1.08)

0.01

0.1

1

Favours EES

10

100

Favours EES

Early, late, and very late ST meta-analysis of six trials. Fixed-effect model (I2 = 3.4%; P = 0.35). CI, confidence interval; EES, everolimus-eluting stent; ST, stent thrombosis; ZES, zotarolimus-eluting stent.

Fig. 5

Study or subgroup

EES Events Total

ZES Odds ratio Events Total Weight (%) M-H, Fixed, 95% CI 40 906 15 1252 36 324 103 1122 15 697

19.4 9.8 16.3 47.1 7.3

0.49 (0.28–0.84) 1.03 (0.56–1.92) 0.78 (0.47–1.31) 0.86 (0.64–1.16) 0.53 (0.22–1.26)

Total (95% CI) 5552 4301 Total events 178 209 Heterogeneity: 2 = 4.80, d.f. = 4 (P = 0.31); I2 = 17% Test for overall effect: Z = 2.47 (P = 0.01)

100.0

0.77 (0.62–0.95)

DUTCH PEERS [14] HOST-ASSURE [13] ISAR-LEFT-MAIN 2 [12] RESOLUTE [7] TWENTE [6]

20 31 29 90 8

905 2503 326 1124 694

0.01

Odds ratio M-H, fixed, 95% CI

0.1 Favours EES

1

10

100

Favours ZES

Target vessel revascularization; meta-analysis of six trials. Fixed-effect model (I2 = 44.0%; P = 0.11). CI, confidence interval; EES, everolimus-eluting stent; ZES, zotarolimus-eluting stent.

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264

Coronary Artery Disease 2015, Vol 26 No 3

Fig. 6

Study or subgroup

EES ZES Events Total Events Total

Odds ratio Weight (%) M-H, Fixed, 95% CI Year

36 324 39 697 33 1252 149 1122 26 906

12.2 13.7 15.9 48.8 9.4

0.78 (0.47–1.31) 0.90 (0.56–1.43) 1.13 (0.74–1.71) 0.88 (0.69–1.13) 1.04 (0.60–1.80)

5552 4301 Total (95% CI) 299 283 Total events Heterogeneity: 2 = 1.59, d.f. = 4 (P = 0.81); I2 = 0% Test for overall effect: Z = 0.88 (P = 0.38)

100.0

0.93 (0.78–1.10)

ISAR-LEFT-MAIN 2 [12] TWENTE [6] HOST-ASSURE [13] RESOLUTE [7] DUTCH PEERS [14]

29 326 35 694 74 2503 134 1124 27 905

Odds ratio M-H, fixed, 95% CI

2013 2013 2014 2014 2014

0.01

0.1

1

Favours EES

10

100

Favours ZES

All-cause mortality meta-analysis of five trials. Fixed-effect model (I2 = 17.0%; P = 0.31). CI, confidence interval; EES, everolimus-eluting stent; ZES, zotarolimus-eluting stent.

Fig. 7

Study or subgroup

EES ZES Odds ratio Events Total Events Total Weight (%) M-H, Fixed, 95% CI 9 324 37 697 17 1252 60 1122

7.3 28.3 18.2 46.2

0.43 (0.13, 1.43) 1.06 (0.67, 1.69) 0.82 (0.45, 1.51) 1.02 (0.70, 1.47)

Total (95% CI) 4647 3395 123 Total events 132 Heterogeneity: 2 = 2.23, d.f. = 3 (P = 0.53); I2 = 0% Test for overall effect: Z = 0.39 (P = 0.70)

100.0

0.95 (0.74, 1.23)

ISAR-LEFT-MAIN 2 [12] TWENTE [6] HOST-ASSURE [13] RESOLUTE [7]

4 326 39 694 28 2503 61 1124

Year

Odds ratio M-H, fixed, 95% CI

2013 2013 2014 2014

0.01

0.1

1

Favours EES

10

100

Favours ZES

Major adverse cardiac event meta-analysis of six trials. Fixed-effect model (I2 = 0.0%; P = 0.41). CI, confidence interval; EES, everolimus-eluting stent; ZES, zotarolimus-eluting stent.

Fig. 8

Study or subgroup ISAR-LEFT-MAIN 2 [12] TWENTE [6] DUTCH PEERS [14] HOST-ASSURE [13] RESOLUTE [7]

EES ZES Odds ratio Events Total Events Total Weight (%) M-H, Fixed, 95% CI Year 46 326 82 694 44 905 158 2503 212 1124

56 324 90 697 58 906 70 1252 210 1122

11.0 18.0 12.5 19.8 38.7

0.79 (0.51–1.20) 0.90 (0.66–1.24) 0.75 (0.50–1.12) 1.14 (0.85–1.52) 1.01 (0.82–1.25)

Total (95% CI) 4301 5552 Total events 542 484 Heterogeneity: 2 = 4.01, d.f. = 4 (P = 0.41); I2 = 0% Test for overall effect: Z = 0.62 (P = 0.53)

100.0

0.96 (0.84–1.10)

Odds ratio M-H, fixed, 95% CI

2013 2013 2014 2014 2014

0.01

0.1 Favours EES

1

10

100

Favours ZES

Subgroup analysis of target vessel revascularization stratified by ZES types. Fixed-effect model (I2 = 44.0%; P = 0.11). CI, confidence interval; EES, everolimus-eluting stent; ; ZES, zotarolimus-eluting stent.

(1.0 vs. 0%, P = 0.002) compared with the ZES group, although none of the patients with LSD had any adverse clinical events. Benching testing showed that EES had

significantly weaker resistance against longitudinal compression, which may have been because of the offset peak–peak design [19]. On analyzing 177 EES-treated

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EES reduced rate of TVR Qi-Hua et al. 265

lesions in 136 patients who underwent intravascular ultrasound, Ota et al. [20] found that EES mechanical complications, often followed by LSD, led to excessive neointimal hyperplasia, in-stent restenosis, and repeat revascularization. This problem has been addressed recently by the manufacturer with the addition of a new version of the EES, the Promus Premier stent. Meanwhile, complex coronary lesion was a strong predictor of TVR and ST [1]. In the ISAR-LEFT-MAIN 2 study [12], which involved patients with unprotected left main coronary artery disease, angiographic restenosis occurred in 21.5% of the patients in the ZES group and 16.8% of the patients in the EES group, and markedly higher TLR rates were observed: 9.4% with EES and 11.7% with ZES versus 2.0% with EES and 2.0% with ZES in patients with less complex coronary lesion (left main lesion, 2%).

5

6

7

8

9 10 11

Study limitations

There were several limitations in our study. Only two studies reported data on very late ST; thus, more randomized trials with a longer follow-up are needed. Meanwhile, our studies are subject to limitations of pooling data from different studies with different patient subgroups, different antiplatelet therapy durations, and follow-up. This is a source of increased heterogeneity. On the basis of the findings of our meta-analysis, future studies will require more patients and careful matching of key clinical variables to definitively address the true effect of EES therapy for patients with coronary artery disease.

12

13

14

15

Conclusion

In summary, our study suggests that at long-term followup, EES and Resolute-ZES showed similar safety and efficacy outcomes. Larger studies with a longer follow-up are needed.

16

Acknowledgements Conflicts of interest

17

There are no conflicts of interest.

References 1 Stefanini GG, Holmes DR Jr. Drug-eluting coronary-artery stents. N Engl J Med 2013; 368:254–265. 2 Alfonso F, Byrne RA, Rivero F, Kastrati A. Current treatment of in-stent restenosis. J Am Coll Cardiol 2014; 63:2659–2673. 3 Palmerini T, Biondi-Zoccai G, Della Riva D, Stettler C, Sangiorgi D, D’Ascenzo F, et al. Stent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis. Lancet 2012; 379:1393–1402. 4 Finn AV, Joner M, Nakazawa G, Kolodgie F, Newell J, John MC, et al. Pathological correlates of late drug-eluting stent thrombosis: strut coverage as a marker of endothelialization. Circulation 2007; 115:2435–2441.

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Li P, Liu JP. Long-term risk of late and very late stent thrombosis in patients treated with everolimus against paclitaxel-eluting stents: an updated metaanalysis. Coron Artery Dis 2014; 25:369–377. Tandjung K, Sen H, Lam MK, Basalus MW, Louwerenburg JH, Stoel MG, et al. Clinical outcome following stringent discontinuation of dual antiplatelet therapy after 12 months in real-world patients treated with secondgeneration zotarolimus-eluting resolute and everolimus-eluting Xience V stents: 2-year follow-up of the randomized TWENTE trial. J Am Coll Cardiol 2013; 61:2406–2416. Taniwaki M, Stefanini GG, Silber S, Richardt G, Vranckx P, Serruys PW, et al. RESOLUTE All-Comers Investigators. 4-year clinical outcomes and predictors of repeat revascularization in patients treated with new-generation drug-eluting stents: a report from the RESOLUTE All-Comers trial (A Randomized Comparison of a Zotarolimus-Eluting Stent With an EverolimusEluting Stent for Percutaneous Coronary Intervention). J Am Coll Cardiol 2014; 63:1617–1625. Moher D, Liberati A, Tetzlaff J, Altman DG, Moher D, Liberati A, et al. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 2009; 62:1006–1012. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7:177–188. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327:557–560. Jüni P, Altman DG, Egger M. Systematic reviews in health care: assessing the quality of controlled clinical trials. BMJ 2001; 323:42–46. Mehilli J, Richardt G, Valgimigli M, Schulz S, Singh A, Abdel-Wahab M, et al. ISAR-LEFT-MAIN 2 Study Investigators. Zotarolimus- versus everolimuseluting stents for unprotected left main coronary artery disease. J Am Coll Cardiol 2013; 62:2075–2082. Park KW, Kang SH, Kang HJ, Koo BK, Park BE, Cha KS, et al. HOSTASSURE Investigators. A randomized comparison of platinum chromiumbased everolimus-eluting stents versus cobalt chromium-based ZotarolimusEluting stents in all-comers receiving percutaneous coronary intervention: HOST-ASSURE (harmonizing optimal strategy for treatment of coronary artery stenosis-safety & effectiveness of drug-eluting stents & anti-platelet regimen), a randomized, controlled, noninferiority trial. J Am Coll Cardiol 2014; 63:2805–2816. Von Birgelen C, Sen H, Lam MK, Danse PW, Jessurun GA, Hautvast RW, et al. Third-generation zotarolimus-eluting and everolimus-eluting stents in allcomer patients requiring a percutaneous coronary intervention (DUTCH PEERS): a randomised, single-blind, multicentre, non-inferiority trial. Lancet 2014; 383:413–423. Armstrong EJ, Feldman DN, Wang TY, Kaltenbach LA, Yeo KK, Wong SC, et al. Clinical presentation, management, and outcomes of angiographically documented early, late, and very late stent thrombosis. JACC Cardiovasc Interv 2012; 5:131–140. Valgimigli M, Tebaldi M, Borghesi M, Vranckx P, Campo G, Tumscitz C, et al. PRODIGY Investigators. Two-year outcomes after first- or secondgeneration drug-eluting or bare-metal stent implantation in all-comer patients undergoing percutaneous coronary intervention: a pre-specified analysis from the PRODIGY study (PROlonging Dual Antiplatelet Treatment After Grading stent-induced Intimal hyperplasia studY). JACC Cardiovasc Interv 2014; 7:20–28. Tada T, Byrne RA, Cassese S, King L, Schulz S, Mehilli J, et al. Comparative efficacy of 2 zotarolimus-eluting stent generations: resolute versus endeavor stents in patients with coronary artery disease. Am Heart J 2013; 165:80–86. Williams PD, Mamas MA, Morgan KP, El-Omar M, Clarke B, Bainbridge A, et al. Longitudinal stent deformation: a retrospective analysis of frequency and mechanisms. EuroIntervention 2012; 8:267–274. Leibundgut G, Gick M, Toma A, Valina C, Löffelhardt N, Büttner HJ, Neumann FJ. Longitudinal compression of the platinum-chromium everolimus-eluting stent during coronary implantation: predisposing mechanical properties, incidence, and predictors in a large patient cohort. Catheter Cardiovasc Interv 2013; 81:E206–E214. Ota H, Kitabata H, Magalhaes MA, Bui A, Kardenas K, Thomas CH, et al. Comparison of frequency and severity of longitudinal stent deformation among various drug-eluting stents: an intravascular ultrasound study. Int J Cardiol 2014; 175:261–267.

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Long-term effect of second-generation drug-eluting stents for coronary artery disease, everolimus-eluting versus zotarolimus-eluting stents: a meta-analysis.

Compared with the zotarolimus-eluting stent (ZES), the everolimus-eluting stent (EES) has reduced the risk of stent restenosis and thrombosis as found...
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