DR YING JIAO ZHAO (Orcid ID : 0000-0001-8820-9463)

Accepted Article
Article type : Original Research Article

A propensity score matched comparison of biodegradable polymer versus

second-generation durable polymer drug-eluting stents in a real-world

population

Ying Jiao Zhao, PhDa, Monica Teng, MHSca, Ai Leng Khoo, PhDa, Rajiv

Ananthakrishna, MBBS, DMb, Tiong Cheng Yeo, MBBS, FACCb,c, Boon Peng Lim,

BPharma, Joshua P. Loh, MBBS, MRCPb,c*, Mark Y. Chan, MBBS, MHSb,c*

a
Pharmacy and Therapeutics Office, Group Corporate Development, National

Healthcare Group, Singapore; bDepartment of Cardiology, National University Heart

Centre, Singapore; cDepartment of Medicine, Yong Loo Lin School of Medicine,

National University of Singapore, Singapore

*These authors supervised the work equally

Corresponding author:

Zhao Ying Jiao

3 Fusionopolis Link

#03-08 Nexus@one-north
This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process, which may
lead to differences between this version and the Version of Record. Please cite this article as
doi: 10.1111/1755-5922.12319
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 Singapore 138543

DID: +65 6496 6693

Accepted Article
Email : ying_jiao_zhao@nhg.com.sg

Short running title: Biodegradable polymer versus durable polymer DES

Abstract

Aims: The safety and efficacy of BP-DES compared to second-generation DP-DES

remain unclear in the real-world setting. We compared the clinical outcomes of

biodegradable polymer drug-eluting stents (BP-DES) with second-generation durable

polymer drug-eluting stents (DP-DES) in an all-comer percutaneous coronary

intervention (PCI) registry.

Methods/Results: The study included a cohort of 1,065 patients treated with either

BP-DES or DP-DES from January 2009 through October 2015. Propensity score

matching was performed to account for potential confounders and produced 497

matched pairs of patients. The primary endpoint was target lesion failure (TLF) at

one-year follow-up. The rates of TLF were comparable between BP-DES and DP-

DES (8.7% versus 9.1%, p=0.823) at one year. The rates of stent thrombosis at 30

days (0.4% versus 0.4%, p=1.00) and one year (0.8% versus 0.8%, p=1.00) did not

differ between BP-DES and DP-DES. There were no significant differences in other

clinical outcomes including target vessel failure (8.9% versus 9.5%, p=0.741), in-

stent restenosis (1.8% versus 1.0%, p=0.282) and cardiac death (6.4% versus 7.4%,

p=0.533) at one year. Multivariate cox regression analysis showed that the risk of

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 TLF at one-year did not differ significantly between BP-DES and DP-DES (hazard

ratio 0.94, p=0.763).

Accepted Article
Conclusions: Efficacy and safety of BP-DES were not better than DP-DES at one-

year follow-up.

Keywords: biodegradable polymer drug-eluting stents, durable polymer drug-eluting

stents, coronary artery disease, target lesion failure

Introduction

New generation drug-eluting stents (DES) with improved polymer biocompatibility or

biodegradable polymer have been designed to overcome the limitations of first-

generation drug-eluting stents.1-3 Biodegradable polymer drug-eluting stents (BP-

DES), as opposed to second-generation durable-polymer drug-eluting stents (DP-

DES), have biodegradable polymer coatings that dissolve after implantation thus

reducing the risk of polymer-related off-target effects such as inflammation, delayed

healing, endothelial dysfunction that could potentially lead to stent thrombosis

(ST).4,5 Prior studies have established the superiority of BP-DES and DP-DES over

first-generation DES in reducing risk of late ST and repeat target-vessel

revascularisation.6-10 Recent evidence derived from systematic review and meta-

analyses of randomised controlled trials showed that BP-DES have similar efficacy

and safety profiles compared with DP-DES in terms of ST, target vessel

revascularisation, MI and death.11-13 However, there is a paucity of data comparing

BP-DES and DP-DES in a real-world setting where patients in clinical practice often

have more complex lesions and other comorbidities.14,15 Given that protocol-driven

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 angiographic follow-up could inflate the incidence of target lesion revascularisation;

observational studies may give a more realistic indication of outcomes and

Accepted Article
complications. We sought to compare the clinical outcomes of BP-DES and second-

generation DP-DES in patients with coronary artery disease (CAD) undergoing

percutaneous coronary intervention (PCI) in real world clinical practice.

Methods

Study design and patients

We conducted a retrospective analysis of patients who had undergone PCI with BP-

DES or DP-DES from January 2009 through October 2015 in a tertiary hospital.

Patients were eligible for inclusion if they underwent a successful PCI with

placement of either single or multiple stents and had completed one-year of clinical

follow-up (hospital visit or telephone assessment) after the procedure. Successful

PCI was defined as the reduction of a minimum in-stent diameter to <20% with a

final Thrombolysis In Myocardial Infarction flow grade 3 at the end of the

procedure.16 The BP-DES studied were biolimus A9 eluting stents (Biomatrix and

Biomatrix Neoflex, Biosensors) and everolimus eluting stents (Synergy I and

Synergy II, Boston Scientific). The DP-DES studied were everolimus eluting stents

(Promus Premier, Boston Scientific; Xience Prime and Xience Xpedition, Abbott

Vascular) and zotarolimus eluting stents (Resolute Integrity and Resolute Onyx,

Medtronic). Patients with implantation of a mixture of DP-DES and BP-DES in the

index PCI procedure were excluded. The index PCI was performed based on

standard guidelines.16 All patients were loaded with aspirin and clopidogrel /

ticagrelor / prasugrel prior to the procedure. Patients were prescribed with dual

antiplatelet therapy (DAPT) for one year after the procedure. Systematic follow-up of

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 all patients was conducted at 30 days and one year by clinical visits or telephone

calls. Ethical approval for the study was obtained from institutional review board.
Accepted Article
Study outcomes

The primary outcomes of interest included target lesion failure (TLF), defined as the

combination of target lesion revascularisation, target vessel-related MI based on The

Third Universal Definition of Myocardial Infarction17 and cardiac death. Target lesion

revascularisation was defined as repeat PCI or coronary artery bypass grafting

(CABG) at the lesion treated during index PCI or lesion in the adjacent 5mm. Target

vessel revascularisation was defined as repeat PCI or CABG at the vessel treated

during the index PCI or any segment of the coronary artery containing the target

lesion. Secondary outcomes were ST (including definite ST and probable ST

according to the Academic Research Consortium definitions18), MI, target vessel-

related MI, target vessel failure (defined as the combined target vessel

revascularisation, target vessel-related MI and cardiac death), in-stent restenosis

(defined by >50% luminal narrowing based on angiographic confirmation18), cardiac

death and all-cause death. All death cases were considered cardiac in origin unless

a noncardiac origin was definitively identified. We also studied major adverse cardiac

events, defined as the composite of MI, target vessel revascularisation and all-cause

death as secondary endpoints. The clinical events were reviewed systematically by

YJZ, MT and ALK and adjudicated separately by RA, JPL, MYC and TCY who were

blinded to the treatment.

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 Statistical analysis

Continuous variables were presented as mean + standard deviation and compared

Accepted Article
between the treatment groups using the Student t-test. Categorical variables were

presented as counts and percentages, and compared between the treatment groups

using Pearson chi-square test or Fisher’s exact test (for frequency of any cell less

than five).

Due to the non-randomised nature of patient recruitment into this study, propensity

score matching was conducted based on logistic regression model to account for

confounders and minimize the treatment selection bias.19,20 Variables previously

shown to be associated with adverse PCI outcomes21 were incorporated into the

propensity score model: age, gender, body mass index, systolic blood pressure,

ethnicity, smoking, indication for PCI due to acute myocardial infarction (AMI)

including ST elevation myocardial infarction (STEMI) and non-ST elevation

myocardial infarction (NSTEMI) patients, diabetes mellitus, hypertension,

dyslipidaemia, premature CAD, peripheral vascular disease, stroke, transient

ischemic attack, chronic renal failure, lesion complexity by American College of

Cardiology/American Heart Association (ACC/AHA) classification,22 intravascular

imaging-guided stenting with intravascular ultrasound or optical coherence

tomography, number of vessels, number of stents, stent width, stent length and prior

history of AMI, PCI and CABG. Patients in BP-DES group and DP-DES group were

matched based on similarity of propensity scores and a matching ratio of 1-to-1 with

no replacement. The difference in means was computed between the two groups for

all covariates, with a standardized mean difference of less than 0.1 indicative of good

balance in the matched cohort.23

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 The cumulative incidence of clinical outcomes was estimated using Kaplan-Meier
Accepted Article
analysis in the matched cohort and the between-group difference was compared

using a log-rank test. Univariate and multivariate Cox proportional hazards models

were used to determine the hazard ratio (HR) and their 95% confidence interval (CI)

for occurrence of events by adjusting for the following characteristics: age, gender,

ethnicity, diabetes mellitus, chronic renal failure, premature CAD, indication for PCI,

lesion complexity, stent width, stent length and number of stents. In subgroup

analyses of TLF, Cox model was used to assess the HR (95% CI) for events rates

within each of the following subgroups: age (≥65), gender, indication for PCI,

diabetes mellitus, lesion complexity, intravascular imaging-guided stenting, number

of vessels and number of stents. We tested for interactions between assigned

treatment and each subgroup using the likelihood-ratio test after estimation. For all

analyses, a two-sided p value of less than 0.05 was considered statistically

significant. All statistical analyses were performed on STATA version 13 (StataCorp.

College Station, TX, USA).

Results

Characteristics of study population

Of 1,065 patients who met the study inclusion criteria, 568 (53.3%) had BP-DES

implantation and 497 (46.7%) had DP-DES implantation. Majority (97.7%) of the

patients received peri-procedural DAPT (71% on aspirin plus clopidogrel, 16.4% on

aspirin plus prasugrel and 10.2% on aspirin plus ticagrelor). The distribution of

antiplatelet agents used was comparable between the two groups. After propensity

score matching, there were 497 matched pairs of patients. Details of the patient and

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 procedural characteristics are shown in Table 1. All variables were well balanced

between the two groups with standardised mean difference less than 0.1
Accepted Article
(Supplemental Table S1).

Clinical outcomes

During the first 30 days of follow up, the TLF rates were numerically higher in DP-

DES compared to BP-DES (6.4% versus 4.2%, p=0.12) in the propensity score

matched population, but the difference did not reach statistical significance (Table 2).

Similarly, there was no difference in other clinical outcomes including ST (0.4%

versus 0.4%, p=1.00) between BP-DES and DP-DES.

At one-year follow-up, the rate of TLF did not differ significantly between BP-DES

and DP-DES (8.7% versus 9.1%, p=0.823) in the propensity score matched

population (Table 2). Similarly, we did not identify any significant difference in other

clinical outcomes including ST (0.8% versus 0.8%, p=1.00), target vessel failure

(8.9% versus 9.5%, p=0.741), in-stent restenosis (1.8% versus 1.0%, p=0.282) and

cardiac death (6.4% versus 7.4%, p=0.533) at one year.

Survival analysis

In the propensity score matched population, the incidence of TLF was not

significantly greater in the BP-DES compared with the DP-DES group (10.1% versus

9.6%, log-rank p=0.80) as shown in Kaplan-Meier curves in Figure 1. Multivariate

Cox regression analysis showed that the risks of TLF were comparable in BP-DES

and DP-DES (HR 0.94, 95% CI 0.61 to 1.43) in Table 3. Older age (HR 1.05, 95% CI

1.03 to 1.07), Malay ethnicity (HR 2.20, 95% CI 1.35 to 3.59), diabetes (HR 1.80,

This article is protected by copyright. All rights reserved.

 95% CI 1.14 to 2.85), chronic renal failure (HR 2.18, 95% CI 1.14 to 4.17) and PCI

performed for AMI (HR 5.17, 95% CI 2.76 to 9.68) were independent predictors of
Accepted Article
TLF (Supplemental Table S2).

Subgroup analysis

The subgroup analysis revealed that the risk of TLF was not lower with BP-DES than

with DP-DES in each of the pre-specified subgroups (Figure 2).

Discussion

New generation DES (BP-DES or DP-DES) have been extensively evaluated in

published studies and demonstrated to be associated with improved efficacy and

safety profiles compared to first-generation DES.6-10 Recent evidence derived from

systematic review and meta-analyses of randomised controlled trials showed that

BP-DES have similar efficacy and safety profiles compared with DP-DES.11-13

However, there is a paucity of clinical data on comparative outcomes between BP-

DES and DP-DES in real-world patients undergoing PCI. Using an all-comers PCI

database, our study did not demonstrate better efficacy and safety with BP-DES than

with DP-DES at one year after stent implantation.

New generation DES have dealt with the limitations observed with first-generation

DES in different ways. DP-DES (or second generation DES) replaced first generation

polymers with more biocompatible polymers. Theoretically, a biodegradable polymer

would abrogate the risk of stent complications from stent polymer exposure. BP-DES

substituted the durable polymer with biodegradable polymers that are designed to be

absorbed after the drug elution process, leaving behind a bare metal stent. At first 30

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 days, there were no significant differences in TLF rates between DP-DES and BP-

DES. This brought to mind whether polymer degradation can be completed within 30
Accepted Article
days and enhance the safety profiles of DES. In the present study, about 90% of

patients in the BP-DES group were treated with Synergy® stent (Boston Scientific) in

which the polymer has been reported to be fully absorbed as early as three months

after stent implantation.24 Therefore, the late benefits of BP-DES are expected to

emerge as early as three to 12 months following stent implantation. Nevertheless,

our findings demonstrated comparable rates of TLF (9.1% versus 8.7%) between

DP-DES and BP-DES at one-year follow-up. These findings corroborated with

COMPARE II, NEXT and EVOLVE II trials that reported similar TLF between BP-

DES and DP-DES (3.7% versus 4.2%, 6.6% versus 6.9% and 6.5% versus 6.7%)

respectively.25-27 Notably, our study reported relatively higher overall TLF event rates

at one year compared with these published trials.25,26 We postulate that this

difference could be attributed to the different study populations analysed. In our

analysis, we included a relatively larger proportion of patients who received PCI due

to AMI compared with to 5% to 50% in RCTs25,26,28 and patients with complex lesions

(75% of patients were grouped as B2/C ACC/AHA lesion class compared with 53%

to 64% in RCTs25,28). About 70% of the event rates of TLF were cardiac deaths. This

higher mortality rate may be a closer reflection of the clinical setting where patients

with cardiogenic shock and comorbidities were included. Similar to findings from a

meta-analysis of 11 trials comparing BP-DES and DP-DES and the SORT OUT VI

trial,12,28 our analysis demonstrated comparable treatment effects on other clinical

outcomes including definite ST, target lesion revascularisation, MI and cardiac death

at one-year follow-up. We further observed a much lower rate of target lesion

revascularisation in our analysis compared to published clinical trials (1.3% versus

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 5.4%).12 This could be explained by the inflated incidence of revascularisation as a

result of protocol-driven follow-up angiography in controlled clinical trials.15

Accepted Article
Conversely, in a real-world setting, only symptomatic patients could be identified and

referred for revascularisation. The safety and efficacy of BP-DES and DP-DES were

similar to that reported in a Korean registry,14 which reported comparable clinical

outcomes at one-year and two-year follow-up.

The pathophysiological mechanisms responsible for late or very late ST are complex

with the persistence of polymer coatings after completion of the drug release being

one of the important factors. The polymer-induced vessel wall inflammation could

result in delayed healing and endothelial dysfunction.4,29 Other factors such as stent

malapposition, neoatherosclerosis and uncovered struts also serve as a source for

future episodes of ST.30 Based on the eventual report of the LEADERS trial,31 the

incidence of definite ST of BP-DES started to emerge at two years and showed

significant difference from two to five years compared with sirolimus-based DP-DES.

In contrast, in the SORT OUT VI study, zotarolimus-based DP-DES and biolimus-

based BP-DES were associated with similar clinical outcomes including ST.32

Therefore, it remain unclear whether the potential benefit of BP-DES in reducing the

risk of late or very late ST might become evident during longer-term follow-up.

We performed subgroup analyses to explore the difference in treatment benefits

between BP-DES and DP-DES based on important and clinical relevant baseline

characteristics including age (> 65 years old), presence of diabetes, presence of

chronic renal failure, index PCI due to AMI and B2/C ACC/AHA lesion class. Notably,

chronic kidney disease has emerged as an important predictor of PCI outcomes

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 regardless of the presence of underlying diabetes mellitus.33,34 In this current study,

we did not detect any significant difference in clinical outcomes between BP-DES
Accepted Article
and DP-DES in subgroups of patients with diabetes or chronic kidney disease.

These findings derived from subgroup analysis need to be interpreted with caution

due to the relatively small sample size of each subgroup.

Given the paucity of data on real-life clinical benefits between BP-DES and DP-DES,

our study provided useful insights on the use of new generation DES in real-world

practice where patients may have more severe coronary artery disease and more

complex lesions. In the present study, we included a relatively larger proportion of

patients who received PCI due to AMI and patients with complex lesions compared

to published trials.25-27 We also analysed both composite endpoints, such as target

lesion revascularisation, and individual endpoints, such as ST and cardiac death, to

gain a more in-depth understanding on the safety profile of new generation DES with

respect to hard clinical endpoints.

Our study should be interpreted in the context of its limitations. Although propensity

score matching was performed to account for potential confounders in treatment

selection, other unmeasured confounding could not be accounted for. In our clinical

practice, as DAPT was prescribed for one year to patients after PCI implanted with

either BP-DES or DP-DES, we were unable to evaluate the impact of differential

DAPT duration. Finally, our findings need to be interpreted with caution due to the

relatively small sample size of each stent group and the low overall incidence of late

ST events may require a larger sample to detect any statistical significant difference

in late ST events.

This article is protected by copyright. All rights reserved.

 Conclusion
Accepted Article
The safety and efficacy of BP-DES were not better than DP-DES at one-year follow-

up in this retrospective analysis of patients undergoing PCI at a tertiary medical

centre. It remains to be determined whether the biodegradable polymer design of

DES could improve outcomes, particularly the risk of very late ST, in longer-term

follow-up studies.

Acknowledgements

The authors acknowledge the assistance provided by Ms Hung Eng Tan and Ms

Fauziah Azizi in data collection and data extraction.

Funding

Mark Y. Chan receives salary support from a National Medical Research Council

Clinician Scientist Award (NMRC/CSA-INV/0001/2016) and Joshua Loh receives

research grant support from Boston Scientific.

Disclosures

All authors declared no conflict of interest.

Author contributors

All authors have contributed significantly to the submitted work and have read and

approved the manuscript. Specifically, Ying Jiao Zhao contributed to concept/design,

data analysis/interpretation, drafting and critical revision of the article. Monica Teng

contributed to concept/design, data analysis/interpretation and critical revision of the

This article is protected by copyright. All rights reserved.

 article. Ai Leng Khoo, Tiong Cheng Yeo and Boon Peng Lim contributed to

concept/design, data interpretation and critical revision of the article. Rajiv

Accepted Article
Ananthakrishna contributed to data collection and interpretation and critical revision

of the article. Joshua P. Loh, Mark Y. Chan contributed to concept/design, data

collection and interpretation and critical revision of the article.

REFERENCES

1. Alfonso F, Fernandez C. Second-generation drug-eluting stents. Moving the field

forward. J Am Coll Cardiol. 2011;58(1):26-29.
2. Lagerqvist B, James SK, Stenestrand U, et al. Long-term outcomes with drug-eluting
stents versus bare-metal stents in Sweden. N Engl J Med. 2007;356(10):1009-1019.
3. Stefanini GG, Holmes DR, Jr. Drug-eluting coronary-artery stents. N Engl J Med.
2013;368(3):254-265.
4. Joner M, Finn AV, Farb A, et al. Pathology of drug-eluting stents in humans: delayed
healing and late thrombotic risk. J Am Coll Cardiol. 2006;48(1):193-202.
5. Rodriguez-Granillo A, Rubilar B, Rodriguez-Granillo G, Rodriguez AE. Advantages
and disadvantages of biodegradable platforms in drug eluting stents. World J Cardiol.
2011;3(3):84-92.
6. Palmerini T, Biondi-Zoccai G, Della Riva D, et al. Stent thrombosis with drug-eluting
and bare-metal stents: evidence from a comprehensive network meta-analysis.
Lancet. 2012;379(9824):1393-1402.
7. Bangalore S, Kumar S, Fusaro M, et al. Short- and long-term outcomes with drug-
eluting and bare-metal coronary stents: a mixed-treatment comparison analysis of
117 762 patient-years of follow-up from randomized trials. Circulation.
2012;125(23):2873-2891.
8. Stefanini GG, Byrne RA, Serruys PW, et al. Biodegradable polymer drug-eluting
stents reduce the risk of stent thrombosis at 4 years in patients undergoing
percutaneous coronary intervention: a pooled analysis of individual patient data from
the ISAR-TEST 3, ISAR-TEST 4, and LEADERS randomized trials. Eur Heart J.
2012;33(10):1214-1222.
9. Navarese EP, Tandjung K, Claessen B, et al. Safety and efficacy outcomes of first
and second generation durable polymer drug eluting stents and biodegradable
polymer biolimus eluting stents in clinical practice: comprehensive network meta-
analysis. BMJ. 2013;347:f6530.
10. Bangalore S, Toklu B, Amoroso N, et al. Bare metal stents, durable polymer drug
eluting stents, and biodegradable polymer drug eluting stents for coronary artery
disease: mixed treatment comparison meta-analysis. BMJ. 2013;347:f6625.
11. El-Hayek G, Bangalore S, Casso Dominguez A, et al. Meta-Analysis of Randomized
Clinical Trials Comparing Biodegradable Polymer Drug-Eluting Stent to Second-
Generation Durable Polymer Drug-Eluting Stents. JACC Cardiovasc Interv.
2017;10(5):462-473.
12. Pandya B, Gaddam S, Raza M, et al. Biodegradable polymer stents vs second
generation drug eluting stents: A meta-analysis and systematic review of randomized
controlled trials. World J Cardiol. 2016;8(2):240-246.

This article is protected by copyright. All rights reserved.

 13. Wang Y, Dong P, Li L, et al. Biodegradable polymer drug-eluting stents versus
second-generation drug-eluting stents for patients with coronary artery disease: an
update meta-analysis. Cardiovasc Drugs Ther. 2014;28(4):379-385.
14. Hur SH, Kim IC, Won KB, et al. Two-Year Safety and Efficacy of Biodegradable
Accepted Article
Polymer Drug-Eluting Stent Versus Second-Generation Durable Polymer Drug-
Eluting Stent in Patients With Acute Myocardial Infarction: Data from the Korea Acute
Myocardial Infarction Registry (KAMIR). Clin Cardiol. 2016;39(5):276-284.
15. Faxon DP. Bringing reality to drug-eluting stents. Circulation. 2004;109(2):140-142.
16. Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI Guideline for
Percutaneous Coronary Intervention: a report of the American College of Cardiology
Foundation/American Heart Association Task Force on Practice Guidelines and the
Society for Cardiovascular Angiography and Interventions. Circulation.
2011;124(23):e574-651.
17. Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial
infarction. Glob Heart. 2012;7(4):275-295.
18. Cutlip DE, Windecker S, Mehran R, et al. Clinical end points in coronary stent trials: a
case for standardized definitions. Circulation. 2007;115(17):2344-2351.
19. Austin PC, Stuart EA. Moving towards best practice when using inverse probability of
treatment weighting (IPTW) using the propensity score to estimate causal treatment
effects in observational studies. Stat Med. 2015;34(28):3661-3679.
20. Austin PC. An Introduction to Propensity Score Methods for Reducing the Effects of
Confounding in Observational Studies. Multivariate Behav Res. 2011;46(3):399-424.
21. Peterson ED, Dai D, DeLong ER, et al. Contemporary mortality risk prediction for
percutaneous coronary intervention: results from 588,398 procedures in the National
Cardiovascular Data Registry. J Am Coll Cardiol. 2010;55(18):1923-1932.
22. Kastrati A, Schomig A, Elezi S, et al. Prognostic value of the modified american
college of Cardiology/American heart association stenosis morphology classification
for long-term angiographic and clinical outcome after coronary stent placement.
Circulation. 1999;100(12):1285-1290.
23. Austin PC. Balance diagnostics for comparing the distribution of baseline covariates
between treatment groups in propensity-score matched samples. Stat Med.
2009;28(25):3083-3107.
24. SYNERGY™ Bioabsorbable Polymer Drug-Eluting Stent System. Product Fact Sheet
2015. Available at http://www.bostonscientific.com/. Accessed 2 December 2016.
25. Smits PC, Hofma S, Togni M, et al. Abluminal biodegradable polymer biolimus-
eluting stent versus durable polymer everolimus-eluting stent (COMPARE II): a
randomised, controlled, non-inferiority trial. Lancet. 2013;381(9867):651-660.
26. Natsuaki M, Kozuma K, Morimoto T, et al. Biodegradable polymer biolimus-eluting
stent versus durable polymer everolimus-eluting stent: a randomized, controlled,
noninferiority trial. J Am Coll Cardiol. 2013;62(3):181-190.
27. Kereiakes DJ, Meredith IT, Windecker S, et al. Efficacy and safety of a novel
bioabsorbable polymer-coated, everolimus-eluting coronary stent: the EVOLVE II
Randomized Trial. Circ Cardiovasc Interv. 2015;8(4).
28. Raungaard B, Jensen LO, Tilsted HH, et al. Zotarolimus-eluting durable-polymer-
coated stent versus a biolimus-eluting biodegradable-polymer-coated stent in
unselected patients undergoing percutaneous coronary intervention (SORT OUT VI):
a randomised non-inferiority trial. Lancet. 2015;385(9977):1527-1535.
29. Luscher TF, Steffel J, Eberli FR, et al. Drug-eluting stent and coronary thrombosis:
biological mechanisms and clinical implications. Circulation. 2007;115(8):1051-1058.
30. Taniwaki M, Radu MD, Zaugg S, et al. Mechanisms of Very Late Drug-Eluting Stent
Thrombosis Assessed by Optical Coherence Tomography. Circulation.
2016;133(7):650-660.
31. Serruys PW, Farooq V, Kalesan B, et al. Improved safety and reduction in stent
thrombosis associated with biodegradable polymer-based biolimus-eluting stents
versus durable polymer-based sirolimus-eluting stents in patients with coronary

This article is protected by copyright. All rights reserved.

 artery disease: final 5-year report of the LEADERS (Limus Eluted From A Durable
Versus ERodable Stent Coating) randomized, noninferiority trial. JACC Cardiovasc
Interv. 2013;6(8):777-789.
32. Raungaard B, Christiansen EH, Botker HE, et al. Comparison of Durable-Polymer
Accepted Article
Zotarolimus-Eluting and Biodegradable-Polymer Biolimus-Eluting Coronary Stents in
Patients With Coronary Artery Disease: 3-Year Clinical Outcomes in the Randomized
SORT OUT VI Trial. JACC Cardiovasc Interv. 2017.
33. Fox CS, Matsushita K, Woodward M, et al. Associations of kidney disease measures
with mortality and end-stage renal disease in individuals with and without diabetes: a
meta-analysis. Lancet. 2012;380(9854):1662-1673.
34. Tonelli M, Muntner P, Lloyd A, et al. Risk of coronary events in people with chronic
kidney disease compared with those with diabetes: a population-level cohort study.
Lancet. 2012;380(9844):807-814.

Table 1. Patient and procedural characteristics in propensity score matched population

Variable DP-DES (N=497) BP-DES (N=497) p value

Age (years) 60.9 ± 11.0 60.9 ± 11.1 0.999

Gender (Male) 408 (82.1%) 412 (82.9%) 0.739

Body mass index (kg/m2) 25.9 ± 3.3 25.9 ± 3.2 0.992

Ethnic

Chinese 310 (62.4%) 322 (64.8%) 0.429

Malay 88 (17.7%) 81 (16.3%) 0.765

Indian 58 (11.7%) 55 (11.1%) 0.555

Others 41 (8.2%) 39 (7.8%) 0.816

Current smoker 157 (31.6%) 157 (31.6%) 1.000

Diabetes 201 (40.4%) 194 (39.0%) 0.650

Dyslipidemia 345 (69.4%) 347 (69.8%) 0.890

Left ventricular ejection fracture (<40%) 70 (18.6%) 88 (17.7%) 0.145

Hypertension 338 (68.0%) 337 (67.8%) 0.946

Systolic blood pressure (mmHg) 135 ± 27 134 ± 26 0.599

Premature coronary artery disease 17 (3.4%) 12 (2.4%) 0.347

Peripheral vascular disease 10 (2.0%) 8 (1.6%) 0.645

Chronic renal failure 31 (6.2%) 29 (5.8%) 0.790

Stroke or transient ischemic attack 33 (6.6%) 32 (6.4%) 0.898

Previous acute myocardial infarction 193 (38.8%) 188 (37.8%) 0.745

Previous PCI 109 (21.9%) 106 (21.3%) 0.817

Previous CABG 25 (5.0%) 25 (5.0%) 1.000

Cardiogenic shock 29 (5.8%) 30 (6.0%) 0.893

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 Index PCI

Acute myocardial infarction 285 (57.3%) 288 (57.9%) 0.847

NSTEMI 225 (45.3%) 231 (46.5%) 0.703

Accepted Article
STEMI 60 (12.1%) 57 (11.5%) 0.768

Multivessel 118 (23.7%) 114 (22.9%) 0.765

ACC/AHA lesion class (B2/C) 382 (76.9%) 384 (77.3%) 0.880

Stent width (mm) 2.8 ± 0.4 2.8 ± 0.5 0.961

Stent length (mm) 26.4 ± 9.4 26.6 ± 8.7 0.795

Number of stents per patient 1.7 ± 0.9 1.6 ± 0.9 0.635

Imaging-guided stenting 64 (12.9%) 57 (11.5%) 0.498

ACC/AHA: American College of Cardiology/American Heart Association; BP-DES: biodegradable polymer drug
eluting stent; CABG: coronary artery bypass graft surgery; DP-DES: second-generation durable polymer drug
eluting stent; NSTEMI: non-ST elevation myocardial infarction; PCI: percutaneous coronary intervention; STEMI:
ST elevation myocardial infarction

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 Table 2. Clinical outcomes in propensity score matched population
Clinical outcomes DP-DES (N=497) BP-DES (N=497) p value
Accepted Article
First 30 days

Target lesion failure 32 (6.4%) 21 (4.2%) 0.120

All-cause mortality 33 (6.6%) 28 (5.6%) 0.509

Cardiac death 31 (6.2%) 21 (4.2%) 0.154

Myocardial infarction 2 (0.4%) 2 (0.4%) 1.000

Target vessel-related myocardial infarction 1 (0.2%) 2 (0.4%) 0.563

Target vessel failure 32 (6.4%) 21 (4.2%) 0.120

Target vessel revascularization 1 (0.2%) 0 0.317

Target lesion revascularization 1 (0.2%) 0 0.317

Major adverse cardiac events 34 (6.8%) 28 (5.6%) 0.431

Stent thrombosis 2 (0.4%) 2 (0.4%) 1.000

Definite 1 (0.2%) 0 0.317

Probable 1 (0.2%) 2 (0.4%) 0.563

One year

Target lesion failure 45 (9.1%) 43 (8.7%) 0.823

All-cause mortality 53 (10.7%) 49 (9.9%) 0.676

Cardiac death 37 (7.4%) 32 (6.4%) 0.533

Myocardial infarction 15 (3.0%) 18 (3.6%) 0.595

Target vessel-related myocardial infarction 8 (1.6%) 10 (2.0%) 0.634

Target vessel failure 47 (9.5%) 44 (8.9%) 0.741

Target vessel revascularization 8 (1.6%) 12 (2.4%) 0.366

Target lesion revascularization 5 (1.0%) 8 (1.6%) 0.402

In-stent restenosis 5 (1.0%) 9 (1.8%) 0.282

Major adverse cardiac events 68 (13.7%) 66 (13.3%) 0.853

Stent thrombosis 4 (0.8%) 4 (0.8%) 1.000

Definite 2 (0.4%) 2 (0.4%) 1.000

Probable 2 (0.4%) 2 (0.4%) 1.000

BP-DES: biodegradable polymer drug eluting stent; DP-DES: second-generation durable polymer drug eluting
stent

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 Table 3. Hazard ratios for clinical outcomes in propensity score matched population at one
year
Accepted Article
Hazard ratio 95% confident
Clinical outcomes p value
(BP-DES versus DP-DES) interval

TLF 0.94 0.61 to 1.43 0.763

All-cause mortality 0.88 0.60 to 1.31 0.539

Cardiac death 0.83 0.51 to 1.33 0.435

Myocardial infarction 1.18 0.59 to 2.35 0.640

Target vessel-related myocardial infarction 1.13 0.44 to 2.93 0.799

Target vessel failure 0.92 0.61 to 1.39 0.689

Target vessel revascularization 1.52 0.61 to 3.78 0.367

Target lesion revascularization 1.86 0.58 to 6.00 0.296

Major adverse cardiac events 0.95 0.67 to 1.33 0.761

In-stent restenosis 2.27 0.73 to 7.07 0.157

Stent thrombosis 0.71 0.16 to 3.16 0.652

Definite 0.86 0.09 to 7.90 0.892

Probable 0.85 0.09 to 7.88 0.885

BP-DES: biodegradable polymer drug eluting stent; DP-DES: second-generation durable polymer drug eluting
stent

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 Figure Legends
Accepted Article
Figure 1. Kaplan-Meier survival curve describing the cumulative incidence of target
lesion failure and stent thrombosis over one year

The cumulative incidence of target lesion failure and stent thrombosis for
biodegradable polymer drug-eluting stents (BP-DES) and second-generation durable
polymer drug-eluting stents (DP-DES) was not statistically significant at one year
after the index percutaneous coronary intervention (PCI).

Figure 2. Subgroup analysis for target lesion failure at one year

The risk for target lesion failure was not significantly different between biodegradable
polymer drug-eluting stents (BP-DES) and second-generation durable polymer drug-
eluting stents (DP-DES) in the pre-specified subgroups.
ACC/AHA: American College of Cardiology/American Heart Association; AMI: acute myocardial
infarction; CI: confidence interval; PCI: percutaneous coronary intervention

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Accepted Article

Figure 1. Kaplan-Meier survival curve describing the cumulative incidence of target lesion
failure and stent thrombosis over one year

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Accepted Article

Figure 2. Subgroup analysis for target lesion failure at one year

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