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Hybrid coronary revascularization versus coronary artery bypass grafting for multivessel coronary artery disease: systematic review and meta-analysis

Journal of Cardiothoracic Surgery201510:63

https://doi.org/10.1186/s13019-015-0262-5

Received: 7 October 2014

Accepted: 17 April 2015

Published: 1 May 2015

Abstract

Background

The concept of hybrid coronary revascularization (HCR) combines the left internal mammary artery (LIMA)–left anterior descending (LAD) graft and percutaneous coronary intervention (PCI) to non-LAD vessels. Multiple comparative studies have evaluated the safety and feasibility of HCR and coronary artery bypass grafting (CABG) for multivessel coronary artery disease (MCAD). However, the sample size of each study was small, and evidences based on single-institutional experience. The purpose of this meta-analysis was to compare the short-term outcomes of HCR with those of CABG for MCAD.

Method

PubMed, EMBASE and Cochrane Library databases, as well as conference proceedings, were searched for eligible studies published up to March 2014. We calculated summary odds ratios (OR) for primary endpoints (death, stroke; myocardial infarction (MI); target vessel revascularization (TVR); major adverse cardiac or cerebrovascular events (MACCEs)) and secondary endpoints (atrial fibrillation (AF); renal failure; length of stay in the intensive care unit (LoS in ICU); length of stay in hospital (LoS in hospital); red blood cell (RBC) transfusion). Data from 6176 participants were derived from ten cohort studies.

Results

HCR was non-inferior to CABG in terms of MACCEs during hospitalization (odds ratio (OR), 0.68, 95% confidence interval (CI), 0.34–1.33)and at one-year follow-up(0.32, 0.05–1.89) , and no significant difference was found between HCR and CABG groups in in-hospital and one-year follow-up outcomes of death, MI, stroke, the prevalence of AF and renal failure, whereas HCR was associated with a lower requirement of RBC transfusion and shorter LoS in ICU and LoS in hospital than CABG (weighted mean difference (WMD) –1.25, 95% CI, –1.62 to –0.88; –17.47, –31.01 to –3.93; –1.77, –3.07 to –0.46; respectively).

Conclusion

Our meta-analysis indicates that HCR is feasible, safe and effective for the treatment of MCAD, with similar in-hospital and one-year follow-up outcome, significantly lower requirement of RBC transfusion, and faster recovery compared with CABG.

Keywords

Hybrid coronary revascularization Coronary artery bypass grafting Multivessel coronary artery disease Meta-analysis

Introduction

The revascularization strategy for multivessel coronary artery disease (MCAD) is associated with advantages and disadvantages. Coronary artery bypass grafting (CABG; on-pump and off-pump) offers superior long-term advantages owing largely to the left internal mammary artery (LIMA) to the left anterior descending (LAD) artery graft [1,2]. Conversely, CABG is a relatively aggressive surgical procedure with a higher risk of postoperative stroke [1,3-5], and conduits via the saphenous vein graft have comparatively short-term patency [6,7]. In contrast, percutaneous coronary intervention, a much less invasive method, carries a minimal procedural risk as well as a lower prevalence of failure for the target vessel due to the use of drug-eluting stents (DES) [8,9]. However, those benefits come at the expense of the need for repeat revascularization [2].

The concept of hybrid coronary revascularization (HCR), which combines the LIMA–LAD graft and percutaneous coronary intervention (PCI) to non-LAD vessels, was first introduced by Angelini and colleagues in 1996 [10]. Introduction of HCR has led to concerns as to whether HCR is superior to CABG for MCAD. Multiple comparative studies have evaluated the safety and feasibility of HCR and CABG for MCAD. However, the sample size of each study was small, and evidences based on single-institutional experience [11-21]. The purpose of this meta-analysis was to compare the short-term outcomes of HCR with those of CABG for MCAD.

Review

Materials and methods

Study selection and search strategy

Two independent reviewers (P.Z, and P.Y.Z) searched PubMed, Embase, Web of Science, and the Cochrane Library for randomized controlled trials (RCTs) and non-RCTs up to 1 March 2014 and compared HCR with CABG for MCAD without language or publication restrictions. The following medical subject heading terms and their variants were used in database searches: hybrid coronary revascularization; coronary artery bypass grafting (on-pump or off-pump); multivessel coronary artery disease. Reference lists within selected studies and abstracts published at major international conferences were also searched.

Outcome measures

The safety endpoints of this meta-analysis were death, stroke, myocardial infarction (MI) and major adverse cardiac or cerebrovascular events (MACCEs). The efficacy endpoint was revascularization. All the primary endpoints were measured in hospital and one year of follow-up. Death was defined as death from any cause. MI was diagnosed by symptoms, electrocardiography and changes in serum levels of cardiac biomarkers. Target vessel revascularization (TVR) was the need for repeated CABG or percutaneous coronary intervention (PCI). MACCEs were defined as a composite of death, MI, stroke or revascularization.

Secondary outcomes were atrial fibrillation (AF), renal failure (defined as an increase in serum creatinine values >25% above baseline values), length of stay in the intensive care unit (LoS in ICU), length of stay in hospital (LoS in hospital), and transfusion of red blood cells (RBCs).

Criteria for eligibility of inclusion of studies

Five main criteria were used: (i) comparison of HCR with CABG for MCAD; (ii) studies reporting at least one of the outcomes mentioned above; (iii) studies documenting surgical procedures such as one-stop HCR or staged HCR, on-pump or off-pump CABG, and documenting surgical methods such as HCR or CABG; (iv) follow-up duration ≥30 days; (v) non-RCTs with a score >5 as assessed by the Newcastle–Ottawa Scale (NOS) [22-24].

Assessment of the methodological quality of included studies

Three independent authors (Y.S., M.M.J, and Y.L.G) assessed the methodological quality of the included studies, and disagreement was resolved by consensus and discussion. Quality of non-RCTs was evaluated with the modified NOS (http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp), which addressed three items: patient selection, comparability of groups, and outcome assessment (Table 1).
Table 1

Newcastle-Ottawa scale used for methodological quality assessment of non-RCT

Check list

 

Selection

 

1、

Assignment for treatment: any criteria reported? (if yes, 1 star)

2、

How representative was the reference group (CABG) in comparison with the general elderly population for CABG? (if yes,1 star; 0 star if the patients were selected or selection of group was not described)

3、

How representative was the treatment group (HCR) in comparison with the elderly population for CABG? (if drawn from the same community as the reference group, 1 star; 0 star if drawn from a different source or selection of group was not described)

Comparability

 

4、

Group comparable for 1, 2, 3, 4,5 (if yes, 2 stars; one star was assigned if one of these five characteristics was not reported even if there were no other differences between the two groups and other characteristics had been controlled for; 0 star was assigned if the two groups differed)

5、

Group comparable for 6, 7, 8,9,10 (if yes, 2 stars; one star was assigned if one of these four characteristics was not reported even if there were no other differences between the two groups and other characteristics had been controlled for; 0 star was assigned if the two groups differed)

Outcome assessment

 

6、

Clearly defined outcome of interest (yes, 1 star for information ascertained by record lincage or interview; 0 star if this information was not reported)

7、

Adequacy of follow-up (1 star if follow-up above 90%)

Comparability variables: 1 = age; 2 = gender; 3 = diabetes; 4 = hypertension; 5 = hypercholesterolemia; 6 = history of cerebrovascular disease; 7 = previous PCI; 8 = previous MI; 9 = smoking; 10 = PVD.

Statistical analyses

We undertook statistical analyses using Revman v5.2 (Cochrane Collaboration, Oxford, UK). Continuous and dichotomous variables were assessed by weighted mean differences (WMDs) and odds ratios (OR), respectively. A 95% confidence interval (CI) was recorded. Heterogeneity among studies was quantified using the I2 statistic. According to Higgins’ method, I2 < 25%, 25–50%, and >50 % were defined as low, moderate, and high heterogeneity, respectively [25]. A fixed-effect model was applied when I2 < 50%, and a random-effect model employed if I2 was >50%. P < 0.05 was considered significant. Sensitivity analyses were done on primary outcomes by changing the effects model and adjusting inclusion criteria. Publication bias was analyzed by funnel plots and evaluated by Egger’s test.

Results

We identified ten studies eligible for inclusion: nine non-randomized and one randomized (Figure 1 and Table 2), All of the non-RCTs had a NOS score >5 [11,12,14,16-21], which was considered to denote a high-quality trial (Table 3). Figure 1 details the process of the identification and selection of studies following the PRISMA statement [26]. Baseline characteristics of patients in the Studies included is shown in Table 4. All studies combined represent outcome data on 6176 patients who underwent HCR(n = 623) or CABG surgery (n = 5553) from 2007 until present.
Figure 1

Flowchart of study identification and selection following PRISMA statement.

Table 2

Main characteristics of included studies

Study

Year

Numbers of patients (HCR/CABG)

Study design

CABG

HCR strategy

Follow-up (months)

Kon [17]

2007

15/30

Non-RCT

OPCABG

Simultaneous

12

Zhao [11]

2008

112/254

Non-RCT

On-pump

Simultaneous

NR

Reicher [14]

2007

13/26

Non-RCT

OPCABG

Simultaneous

14

Vassiliades [12]

2009

91/4175

Non-RCT

OPCABG

PCI then MICABG

12

6.6%

MICABG then PCI

93.4%

Delhaye [20]

2010

18/18

Non-RCT

On-pump

CABG then PCI

12

OPCABG then PCI

Hu [18]

2010

104/104

Non-RCT

OPCABG

Simultaneous

18 ± 7.9

Halkos [19]

2011

147/588

Non-RCT

OPCABG

Mainly staged

38.4 (median)

Bachinsky [21]

2012

25/27

Non-RCT

OPCABG

Simultaneous

1

Leacche [16]

2012

80/301

Non-RCT

OPCABG

NR

1

Popov [15]

Unpublished

18/30

RCT

On-pump

MICABG then PCI

1

Unless otherwise indicated, data are expressed as mean ± standard deviation.

PCI, percutaneous coronary intervention; OPCABG, on-pump coronary artery bypass grafting; MICABG, minimally invasive coronary artery bypass grafting; NR: not reported.

Table 3

Assessment of quality of studies

  

Selection

 

Comparability

 

Outcome assessment

  

Author

Year

1

2

3

4

5

6

7

Score

Kon

2007

*

*

*

*

**

*

-

*******

Zhao

2008

-

*

*

**

*

*

-

******

Reicher

2007

*

*

*

**

**

*

-

********

Vassiliades

2009

*

*

*

**

*

*

*

********

Delhaye

2010

*

*

*

**

*

*

-

*******

Hu

2010

*

*

*

**

**

*

*

*********

Halkos

2011

*

*

*

*

*

*

-

******

Bachinsky

2012

-

*

*

**

**

*

-

*******

Leacche

2012

-

*

*

**

*

*

-

******

-:zero point, *: One point, **: Two points.

Table 4

Baseline characteristics of Patients in the Studies included

Author

Group

N

Age (y)

Male (%)

Diabetes (%)

Hypertension (%)

Previous MI (%)

History of cerebrovascular disease (%)

Smoking (%)

Kon

HCR

15

61 ± 10

73

27

87

67

7

27

 

CABG

30

65 ± 10

63

40

80

57

0

33

Zhao

HCR

112

63(32–85)

71

39

82

17

8

68

 

CABG

254

63(32–89)

76

39

83

12

8

63

Reicher

HCR

13

62 ± 10

80

29

87

47

0

36

 

CABG

26

64 ± 10

83

41

75

50

0

36

Vassiliades

HCR

91

65 ± 14

67

41

82

42

17

53

 

CABG

4175

63 ± 12

69

37

83

48

18

69

Delhaye

HCR

18

62(55–70)

78

45

67

28

11

44

 

CABG

18

60(53–68)

78

39

78

17

0

39

Hu

HCR

104

62 ± 10

11

25

60

34

9

56

 

CABG

104

62 ± 8

20

27

63

29

6

37

Haloks

HCR

147

64 ± 13

62

60

87

17

20

42

 

CABG

588

64 ± 13

71

64

85

12

17

50

Bachinsky

HCR

25

63 ± 11

80

36

72

20

4

28

 

CABG

27

67 ± 11

59

48

96

44

15

22

Leacche

HCR

80

64

76

40

86

16

6

NR

 

CABG

301

63

77

37

83

16

10

NR

Popov

HCR

18

60 ± 6

86

16

100

NR

14

NR

 

CABG

30

59 ± 4

83

17

100

NR

0

NR

Data between parentheses represent median and 25th and 75th percentiles. Data with ± symbol represent mean and SD.

Early outcomes (in hospital)

Primary clinical outcomes

Death

Five studies reported on in-hospital mortality in 5770 patients. Pooled results showed no significant difference in mortality between the HCR group and CABG group <1 month (OR: 1.21; 95% CI: 0.55–2.62; P = 0.64; Figure 2A).
Figure 2

Forest plot showing a meta-analysis for HCR versus CABG during hospitalization. A. Death B. MI(Myocardial Infarction) C. Stroke D. MACCEs (Major Adverse Cardiac or Cerebrovascular Events).

MI

Patients treated with HCR did not display a significant reduction in risk for MI as compared with those who received CABG within hospital (OR: 0.69; 95% CI: 0.21–2.24; P = 0.54; Figure 2B). Heterogeneity was not observed in this analysis (I2 = 3%).

Stroke

Stroke was assessed in five studies reporting on 5793 patients. The prevalence of stroke was not significantly different between groups. (OR: 1.12; 95% CI: 0.44–2.86; P = 0.81; Figure 2C). Heterogeneity was not observed in this analysis (I2 = 0%).

TVR

We analyzed the prevalence of TVR described in the five articles. For four studies, no event occurred in both groups, so we could not undertake a meta-analysis on the prevalence of TVR. In summary, there was insufficient evidence to show that the prevalence of TVR was different between HCR group and CABG group.

MACCEs

MACCEs occurred in 2.5% (10/408) of patients after HCR and 3.6% (181/5092) of patients with CABG.Six studies (5500 patients) provided data on the prevalence of MACCEs. Pooling of the outcomes of these studies revealed no significant differences in the prevalence of MACCEs between patients treated by HCR and those treated by CABG (OR: 0.68; 95% CI: 0.34–1.33; P = 0.26; Figure 2E). Slight heterogeneity was detected in this analysis (I2 = 2%).

Secondary clinical outcomes

Five studies reported on AF. [11,16,18,19,21] Four studies reported renal failure [11,16,17,19,20]. Six studies reported LoS in ICU [14,15,17-19,21]. Five studies reported LoS in hospital [14,17-19,21]. Three studies reported transfusion of RBCs [14,17,21].

There was no significant difference in the prevalence of AF between the two groups (OR: 0.93; 95% CI: 0.70–1.23, P = 0.60) or the prevalence of renal failure (OR: 0.73; 95% CI: 0.36–1.49; P = 0.39).

HCR was associated with a significantly shorter LoS in ICU (29.99 vs.47.85 h; WMD: −17.47 h; 95% CI: −31.01 to −3.93; P = 0.01), LoS in hospital (5.44 vs. 7.30 days; WMD: −1.77 days; 95% CI, −3.07 to −0.46; P = 0.008), and fewer instances of RBC transfusion (0.26 vs. 1.55U; WMD: −1.25 U; 95% CI, −1.62 to −0.88; P < 0.001) (Table 5).
Table 5

Results of meta-analysis of the secondary outcome

Outcome measures

Number of studies

Patients (HCR/CABG)

I2 (%)

Analysis model

Statistics method

OR/WMD

95% CI

p value

AF

5

468/1274

0

Fixed

M-H

0.93

0.70,1.23

0.60

Renal Failure

5

372/1191

0

Fixed

M-H

0.64

0.32,1.27

0.20

Intubation Time

3

132/160

93

Random

IV

−9.95

−18.58,-1.31

0.02

LOS in ICU

6

322/805

85

Random

IV

−17.47

−31.01,-3.93

0.01

LOS in hospital

5

304/775

82

Random

IV

−1.77

−3.07,-0.46

0.008

Red Blood Cells Transfusion

3

53/83

0

Fixed

IV

−1.25

−1.62,-0.88

P<0.00001

OR odds ratio, WMD Weighted mean difference, M–H Mantel–Haenszel, IV inverse variance, CI confidence interval, AF atrial fibrillation, LOS in ICU lengths of stay in Intensive Care Unit, LOS in hospital lengths of stay in hospital.

Longer-term outcomes (One year of follow-up)

MACCEs occurred in 2.9% (4/137) of patients after HCR and 11.8% (18/152) of patients with CABG at one year of follow-up. The ORs for MACCEs were not significantly different at one year of follow-up (OR: 0.32; 95% CI: 0.05–1.89, P = 0.21; Figure 3E ). As shown in Figure 3A, 3B, 3C, and 3D, overall, the outcomes for death, MI, Stroke and TVR at one year of follow-up were not statistically different.
Figure 3

Forest plot showing a meta-analysis for HCR versus CABG at one-year of follow up. A. Death B. MI(Myocardial Infarction) C. Stroke D. TVR (Target Vessel Revascularization) E. MACCEs (Major Adverse Cardiac or Cerebrovascular Events).

Sensitivity analyses and publication bias

Sensitivity analyses were undertaken on the outcomes mentioned above by re-analyses using a different effects model by including studies with ≥80 patients in each group and including non-RCTs with a score >6 as assessed by the NOS.

Analyses of non-RCTs studies with a score >6 separately also did not substantively alter the overall result of our analyses. Moreover, changing the model did not substantially change the pooled point estimate.

Inclusion of studies with ≥80 patients in each group did not substantially change the pooled point estimate except for LoS in ICU and LoS in hospital. Pooling the outcomes of these studies revealed no significant difference in the LoS in ICU (WMD: −10.47 h, 95% CI: −35.00 to 14.07; P = 0.40) or LoS in hospital (WMD: −0.42 days; 95% CI: −2.19 to 1.34; P = 0.64) between the two groups.

In summary, the results of sensitivity analyses supported the credibility of most of the evidences in this meta-analysis, but the credibility of the evidences about LoS in ICU and LoS in hospital should be considered carefully.

Also, we assessed for publication bias of data by Egger’s test and visual assessment of funnel plots. For the endpoint of in-hospital MACCEs, Egger’s test revealed P = 0.694, showing no evidence of publication bias.

Discussion

In this meta-analysis, HCR was non-inferior to CABG in terms of in-hospital and one-year follow-up outcomes of death, MI, stroke, TVR, MACCEs, and some surgical complications (including AF and renal failure) whereas HCR was associated with a reduced need for RBC transfusion as well as shorter LoS in ICU and LoS in hospital than CABG.

We revealed no significant differences in the prevalence of in-hospital and one-year follow-up mortality, MI, stroke, TVR, MACCEs between the two groups, findings which were consistent with the early results of an ongoing RCT [15]. In that RCT, there was no mortality, MACCEs, or TVR in the hospital. The adequate design of that study (a prospective, randomized pilot trial to compare HCR with CABG in patients with MCAD) provided the preliminary data to strengthen the evidences of our study.

The prevalence of in-hospital one-year follow-up mortality, MI, stroke and MACCEs were similar between the two groups, however, we hypothesized that HCR may be superior to CABG in terms of long-term MACCEs. Hu et al. [18] reported a lower prevalence of MACCEs after HCR compared with on-pump CABG (1.0% vs 9.6%) after a mean follow-up of 18 months. Shen et al. [13] also reported that, after a mean follow-up of 3 years, in the high Euro-SCORE tertile, the prevalence of MACCEs in the hybrid group was significantly lower than that in the CABG group (P = 0.030).

As duration of follow-up extends, HCR may be superior to CABG in terms of long-term MACCEs.Several reasons support this findings mentioned above. Firstly, avoiding aortic clamping is one of the unique advantages of the hybrid procedure. Aortic manipulation (a predictor of postoperative cerebral infarction) is necessary during on-pump CABG [27]. Secondly, in the hybrid procedure, the quality of LIMA–LAD grafting is confirmed further by prompt angiography and deficiencies can be corrected immediately and reliably [28-30]. Finally, the less invasive nature of the hybrid procedure plays an important part in patient recovery.

Cardiac surgery and administration of contrast dyes during PCI tends to increase the risk of renal failure. Hence, we suggest that the prevalence of renal dysfunction might be higher in patients treated with HCR compared with those undergoing CABG alone. In this meta-analysis, however, no significant difference in the prevalence of renal failure was found between the two groups. The more stable hemodynamics and better urine output in the hybrid group may have resulted in a similar prevalence of renal failure in the present study [31,32].

In this analysis, the significantly lower requirement of RBC transfusion in the HCR group was attributed to the less invasive nature of minimally invasive direct coronary artery bypass grafting in the hybrid procedure despite continuous perioperative use of aspirin and perioperative administration of clopidogerl [12,14,31].

LoS in ICU and LoS in hospital were significantly shorter in the HCR group in this analysis, so the hybrid group had a shorter recovery with a substantial reduction in utilization of hospital resources [33]. This phenomenon could be explained in two ways. Firstly, a lower requirement of blood transfusion and reduced systemic inflammation have been associated with improved postoperative morbidity in a series of studies comparing minimally invasive and conventional surgery, and probably play a part in the outcomes of hybrid surgery. Secondly, better myocardial protection (as reflected by a reduction in regional release of myoglobin and systemic release of troponin I) might be another mechanism for quicker recovery after the hybrid procedure [17].

Heterogeneity among studies was observed for several continuous variables, including LoS in ICU and LoS in hospital. This heterogeneity may have resulted from variations in the surgeon’s caseload, the learning-curve effect, the HCR procedure, perioperative management, and standards regarding hospital discharge among the included studies.

Limitations

This meta-analysis had several limitations. The main limitation of our meta-analysis was the retrospective nature of the available data. No RCT has been published but two protocols have been registered (available at http://www.clinicaltrials.gov/ct2/show/NCT01699048 and http://www.clinicaltrials.gov/ct2/show/NCT01035567). Ideally, a meta-analysis should include RCTs only, but inclusion of high-quality non-RCTs can improve the statistical power while maintaining an acceptable level of evidence. Abrahama et al. [34] reported that a meta-analysis of well-designed comparative non-RCTs of surgical procedures was as accurate as a meta-analysis of RCTs. Also, evaluation of publication bias cannot be done in a robust manner with such few data points, so the statistical power of Egger’s test to alert suspicion of publication bias was very limited in our meta-analysis. Therefore, more RCTs comparing HCR with CABG in patients with MCAD are necessary.

Secondly, the duration of clinical follow-up was limited to one year in most studies, whereas a meta-analysis of long-term outcomes was not possible due to insufficient data [12,13,17,18,20]. Hence, more long-term results will be necessary for future studies.

Thirdly, the definition of endpoints such as MI, MACCEs, and renal failure in different studies varied to some degree, which may have weakened the evidences in our analysis.

Finally, obvious heterogeneity was observed for several continuous variables. Therefore, the random-effects model was used.

Conclusion

This meta-analysis suggested that HCR is feasible, safe and effective for treatment of MCAD, with similar in-hospital and one-year follow-up outcomes, significantly lower requirement for RBC transfusion, and faster recovery compared with CABG. It may provide a safe and effective alternative for treating selected patients with MCAD. However, to validate the long-term results of HCR for MCAD, more large-scale, multicenter, prospective RCTs are warranted.

Abbreviations

HCR: 

Hybrid coronary revascularization

CABG: 

Coronary artery bypass grafting

MCAD: 

Multivessel coronary artery disease

OR: 

Odds ratios

MI: 

Myocardial infarction

TVR: 

Target vessel revascularization

MACCEs: 

Major adverse cardiac or cerebrovascular events

AF: 

Atrial fibrillation

LoS: 

Length of stay

ICU: 

Intensive care unit

RBC: 

Red bloodcell

CI: 

Confidence iinterval

WMD: 

Weighted mean difference

LIMA: 

Left internal mammary artery

LAD: 

Left anterior descending

DES: 

Drug-eluting stents

PCI: 

Percutaneous coronary intervention

RCTs: 

Randomized controlled trials

NOS: 

Newcastle–ottawa scale

Declarations

Acknowledgments

We thank Professor Vadim Popov (Chief of Cardiac Surgery, Kemerovo Center of Cardiology and Cardiac Surgery, Kemerovo Oblast, Russia) for providing additional data pertaining to their ongoing RCT (Available at: http://www.clinicaltrials.gov/ct2/show/NCT01699048).

Authors’ Affiliations

(1)
Department of Cardiovascular Surgery, Southern Medical University
(2)
Department of Cardiovascular Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences
(3)
Department of Cardiovascular Surgery, Xiamen Heart Center

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