Clinical Research Artical
 

Treatment of Patients with Coronary Artery Disease with Biodegradable
Polymer Based Paclitaxel-Eluting Infinnium® Coronary Stent System:
Results of 1-Year Clinical Follow-up
A Single Center Experience

Aytekin Vedat1 , Gormez Selcuk2, Erdim Refik2, Erdogmuş Onur2, Civan Murat1,
Catakoglu Alp Burak2, Gulbaran Murat1, Demiroglu Cemsid1

1 Florence Nightingale Hospital, Department of Cardiology, Istanbul, Turkey
2 Istanbul Bilim University, Department of Cardiology - Florence Nightingale Hospital, Istanbul, Turkey

ABSTRACT

Objectives: Evaluating the efficacy of the Infinnium® paclitaxel-eluting coronary stent system with the biodegradable polymer in the treatment of symptomatic coronary artery disease.
Methods and Results: Total 153 patients were treated with native coronary artery lesion treated with Infinnium® paclitaxel-eluting coronary stent system. This study was a single centre, non-randomized, retrospective study. At baseline diabetes, hypertension and smoker patients were present in 53 (35%), 112 (73%) and 80 (52%) respectively. The number of patients with unstable angina and acute MI on admission was 48 (31%) and 7 (5%) respectively. Patients with left ventricular ejection fraction less than 40 % were 18 of the study population. Clinical information was collected 1, 3, 6 and 12 months after procedure. Major adverse cardiac event was defined as death, non-fatal myocardial infarction and target vessel revascularization. Cumulative MACE rates were 5 (3.3%) in first month, 6 (3.9 %) in 3 months, 9 (5.9 %) in 6 months and 15 (9.8%) in 1-year. At the end of 1-year follow-up period, TVR was 7.8% (12 Patients), which included 8 (5.2%) PCI and 4 (2.6%) CABG Patients. 1-year survival without MACE was 90.2 %
Conclusion: This study demonstrates that the Infinnium® paclitaxel-eluting coronary stent system with the biodegradable polymer in the treatment of symptomatic coronary artery disease is a concurrent with current standard of treatment.

Keywords: drug-eluting stents, percutaneous coronary intervention, coronary artery disease

Introduction


The development of drug-eluting stents (DES) for the treatment of coronary lesions is one of the major progress in the field of interventional cardiology due to it is considerable efficacy in reducing in-stent restenosis compared to bare-metal stents (BMS). Several pharmaceutical agents, particularly sirolimus and paclitaxel, have demonstrated marked anti-proliferative and anti-inflammatory effects in numerous clinical trials1-5. However, many studies involving DES with permanent polymer coating reported more late stent thrombosis compare to BMS which persist definetly.6-9. Permanent polymer-coating which presents indefinitely on the stent surface after drug elution has been proposed to trigger long-term adverse cardiac events due to local inflammatory reaction10-12. Therefore, better alternative coatings such as biodegradable polymers have been developed to figure out the issue. It is believed that to prevent chronic irritation on arterial wall and this might improve

endothelialization and reduce possibility of late stent thrombosis. However, the ability of new generation of biodegradable polymer coating DES is not fully documented till now. With this goal, in current study we assessed 1-year clinical follow-up results of real-life coronary artery patients treated with biodegradable polymer based paclitaxel-eluting Infinnium® coronary stents (Sahajanand Medical Technologies Pvt. Ltd, India).


METHODS: In our center, a total of 194 coronary artery Patients were implanted with Infinnium® stents between July, 2006 and August, 2008. We evaluated 153 Patients who completed 1-year follow-up period, retrospectively. 113 of Patients (73.9%) were male and mean age was 57.9 ± 10.1. Clinical characteristics of Patients are summarized in Table 1. Written informed consent had been taken from all Patients before the interventions. Percutaneous coronary intervention (PCI) procedures were performed by standard percutaneous techniques using the femora

 

Correspondence: Dr. Vedat Aytekin MD, FESC Professor of Cardiology Istanbul Bilim University Florence Nightingale Hospital Abide-i Hurriyet Cd No:290/1 34403 Sisli, Istanbul-Turkey
E-mail:
[email protected], Phone :  +90 212 224 49 50 ( Ext: 4099), Mobile Phone :   +90 532 236 84 87, Fax :  +90 212 296 52 22

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Treatment of CAD with Biodegradable Polymer
 

approach and standard stent applications as described previously. A total of 203 Infinnium® stents were implanted for 192 lesions and mean number of stents per case was 1.33 ± 0.6. All Patients’ 12-lead electrocardiography records were collected before and after the procedure. Blood samples for Creatine Kinase-MB (CKMB) enzymes were also routinely drawn before the PCI and at 6 and 24 hours after intervention. Digital coronary angiograms were analyzed offline by an expert operator blinded to the procedure using Philips QCA-DCI software. Minimal lumen diameter (MLD), reference vessel diameter (RVD) and percent diameter stenosis at baseline and post-procedure were measured, respectively. Dual-antiplatelet therapy was given at least for 12-months following the procedure.
All Patients were clinically followed-up by hospital visits at 30-day, three-month, six-month and 1-year. Major adverse cardiac event (MACE) was defined as death, non-fatal myocardial infarction (MI) (ST-elevated or non ST-elevated) and target vessel revascularization (TVR). TVR was defined as all ischemia-driven PCI and/or coronary by-pass graft surgery (CABG). ST-elevation MI was defined as presence of new pathological Q waves in the electrocardiogram (ECG) associated with an elevation of CKMB enzyme elevation ≥ 3 x the upper limit of the normal value. A non-ST elevation MI was defined as CKMB enzyme elevation ≥ 3 x the upper limit of the normal value without new pathological Q waves in the ECG. All deaths were considered as cardiac unless otherwise recorded. Stent thrombosis was classified as definite, probable, or possible in accordance with criteria developed in 2006 by the Academic Research Consortium. Early stent thrombosis included all events occurring within 30 days of PCI, late stent thrombosis included those occurring between 31 to 360 days after PCI13. Procedural success was defined as successful stent deployment and residual stenosis < 30% with TIMI III flow measured by quantitative coronary angiography software, unless MACE occurred during in-hospital period. Lesion complexity was analyzed according to the modified American College of Cardiology/American Heart Association grading classification14.

Statistical Analysis:

Statistical analysis was performed using SPSS statistical software package (version 15.0 for Windows, SPSS Inc. Chicago, Illinois). Categorical variables were expressed as frequencies and continuous variables as mean ± 1 standard deviation. Survival free of MACE was estimated using the Kaplan-Meier method.

RESULTS:

The Patients in our study population were in high-risk group that reflects real-world experience. Approximately one-third of the Patients had diabetes. The rate of unstable angina and acute MI on admission was 31.4 % and 4.6 % respectively. Patients with

 

n = 153

Age, years , (mean ±SD)

57.9 ± 10.1

Male gender, n (%)

113 (73.9)

Family history of CAD

60 (39.2)

Hypertension

112 (73.2)

Hyperlipidemia

127 (83)

Diabetes mellitus

53 (34.6)

Smoking

80 (52.3)

Previous MI

56 (36.6)

Previous PCI

30 (19.6)

Previous CABG

15 (9.8)

LVEF < 40%

18 (11.8)

Acute MI

7 (4.6)

Unstable angina

48 (31.4)

CABG: Coronary artery bypass graft; CAD: Coronary artery disease; MI: Myocardial infarction; PCI: Percutaneous coronary intervention; LVEF: Left ventricular ejection fraction.
left ventricular ejection fraction less than 40 % were 11.8 % of the study population. 9.8 % of Patients had undergone CABG and 36.6 % had an history of previous MI. Almost three-fourth of lesions treated with PCI were complex lesions (B2/C).  The rate of bifurcation lesion was 6.3 %. Total occlusion and in-stent restenosis rates were 8.3 % and 6.3 %, respectively. More than 50 % of lesions were localized in left anterior descending coronary artery and the frequency of saphenous vein graft lesions was 5.1 %. Procedural success rate was 98 %. The usage of distal protection device (AngioGuard ™, Cordis Corp., Miami, Florida and Filterwire EX ™ , Boston Scientific Corp


Table 2.
Procedural characteristics

 

n = 153

Number of stents per patient, (n)

1.33 ± 0.6

Stent diameter (mm)

3.04 ± 0.3

Stent length (mm)

25.7 ± 7.9

Lesion length (mm)

23.2 ± 6.8

Reference vessel diameter (mm)

2.92 ± 0.3

Pre-intervention diameter stenosis (%)

83.3 ± 11.6

Post-intervention diameter stenosis (%)

6.2 ± 2.0

Pre-intervention MLD (mm)

0.50 ± 0.37

Post-intervention MLD (mm)

2.85 ± 0.33

Maximum balloon inflation, atm

14.92 ± 3.02

Procedural success, n (%)

150 (98)

Overlapping stent, n (%)

27 (14.1)

Usage of distal protection devices, n (%)

4 (2.6)

Usage of GP inhibitors, n (%)

8 (5.2)

 

GP: Glycoprotein , MLD: Minimal luminal diameter,
Plus-minus values are means ±SD

 

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Natick, Massachusetts) and glycoprotein IIb/IIIa inhibitors (AGGRASTAT®, Merck Sharp & Dohme Co, New Jersey, USA) were 2.6 % and 5.2 %. Lesion and procedural characteristics of Patient are summarized in Table 2 and Table 3.

Non-ST elevation MI occurred in 3 Patients (2 %) and ST-elevation MI in 1 (0.7) Patient during in-hospital stay.
 

Table 3. Lesion characteristics

Location of lesion,  (%)

 

                  Left anterior descending artery

52.6

                  Left circumflex artery

15.2

                  Right coronary artery

25.5

                  Saphenous vein graft

5.1

                  Intermediate coronary artery

1.1

                  Left internal mammarial artery

0.5

Lesion classification * , n (%)

n:192

                 A

12 (6.2)

                 B1

34 (17.7)

                 B2

42 (21.9)

                 C

104 (54.2)

Ostial lesion, n (%)

4 (2.1)

Bifurcation lesion, n (%)

12 (6.3)

Total occlusion, n (%)

16 (8.3)

In-stent restenosis, n (%)

12 (6.3)

Thrombus, n (%)

21 (10.1)

* Lesion complexity was analyzed according to American College of Cardiology/
American Heart Association grading classification.

 

. Cumulative MACE rates were 3.3% in first month, 3.9 % in 3 months, 5.9 % in 6 months and 9.8% in 1-year. At the end of 1-year follow-up period, TVR was 7.8% (12 Patients), which included 8 (5.2%) PCI and 4 (2.6%) CABG patients. Early (acute) stent thrombosis occurred in one patient. Neither death nor late stent thrombosis occurred during follow-up period (Table 4). 1-year survival without MACE was 90.2 % (Figure 1).

DISCUSSION:
 

Table 4. In-hospital, 6-month and 1-year clinical outcomes (n=153)

 

In-hospital
n, (%)

1-month
n, (%)

3-month
n, (%)

6-month
n, (%)

1-year
n, (%)

NSTEMI

3 (2.0)

3 (2.0)

3 (2.0)

3 (2.0)

3 (2.0)

STEMI

1(0.7)

1(0.7)

1(0.7)

1(0.7)

1(0.7)

TVR

1 (0.7)

2 (1.3)

3(2.0)

5 (3.3)

12(7.8)

          PCI

1(0.7)

2 (1.3)

2 (1.3)

4 (2.6)

8 (5.2)

          CABG

0

0

1 (0.7)

1 (0.7)

4 (2.6)

Death

0

0

0

0

0

Cumulative MACE

4 (2.6)

5 (3.3)

6 (3.9)

9 (5.9)

15 (9.8)

Early stent thrombosis

1 (0.7)

1 (0.7)

1 (0.7)

1 (0.7)

1 (0.7)

Late stent thrombosis

0

0

0

0

0

CABG: Coronary artery bypass graft,  MACE: Major adverse cardiac events, NSTEMI: Non-ST elevation myocardial infarction; PCI: Percutaneous coronary intervention; STEMI: ST elevation myocardial infarction; TVR: Target vessel revascularization.

 

 

 
 

Permenant or biodegradable polymer-based coatings can be used as a platform for local drug delivery in DES. First generation stents, which is used especially with off-label indication, suspected to cause late stent thrombosis because of their permanent polymer coating. In our study we preferred biodegradable polymer-based Infinnium® stent, which is made up of Millennium Matrix® stainless steel stent as a platform and biodegradable polymer coating releasing paclitaxel as an anti-proliferative agent. Paclitaxel (Taxol; Bristol-Myers Squibb), a natural compound extracted from the Pacific yew tree Taxus Brevifolia, has been shown to act via microtubule stabilization, arrest of cell mitosis, retardation of cell migration and immuno-modulation15-17. Paclitaxel concentration on the surface is 1.4μg/mm2. The polymer coating differs from the other permanent polymer based paclitaxel-eluting stents as being biocompatible and biodegradable (poly L-lactide, 50/50 poly DL-lactide-co-glycolide, 75/25 poly L lactide-co-caprolactone and polyvinyl pyrrolidone). 50% of the drug is delivered in the first 9 days and 90% in 38 days following the implantation whereas the entire drug is depleted in 48 days18. However, permanent polymer coated stents complete their paclitaxel release within 30 days of implantation, although a substantial portion (>90%) of the paclitaxel remains within the polymer indefinitely which may cause adverse cardiac outcomes.

Infinnium® stent was issued in several prospective studies. SIMPLE I study which enrolled 282 real-life patients was showed 87.6% event-free survival rate after 36 months of follow-up. Also in the SIMPLE II study included 103 patients with a single, de novo, focal lesion, the rate of MACE was reported as 9.7% for 9 months18. SIMPLE III trial included 123 patients with multi-vessel coronary artery disease. Major cardiac event rate was found 9.7% at 12 months. SIMPLE trials showed that biodegradable polymer coated paclitaxel-eluting Infinnium® stent provided comparable results with Taxus TM trials at the end of 1-year follow-up19-22.

 

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. In our study we found that the rate of MACE was 9.8% at 1-year follow-up which is comparable with the results of SIMPLE I and Taxus IV trials including real-world high-risk population. In a recent multi-center, prospective trial which enrolled 116 Patients with single de novo coronary lesion and conducted with biodegradable polymer-coated, paclitaxel eluting Luc-Chopin stents, the total incidence of MACE was found 7.8% at 12 months23. Our results is also comparable with this study which conducted with relatively low risk Patients. We detected only one case of acute stent thrombosis which was diagnosed as acute coronary syndrome on admission, therefore it did not seem to be related with stent coatings. The safety profile of the Infinnium® stent was excellent as no subacute or late stent thrombosis was recorded in 1-year follow-up.

In summary, findings of our study suggest that biodegradable polymer-coated, paclitaxel eluting Infinnium® coronary stent seems to be safe and effective in the treatments of real-world Patients at 1-year. Further randomized, head-to-head studies with larger Patients are needed between permanent and biodegradable paclitaxel-eluting stents.

STUDY LIMITATION:
Our study was limited by its nature of being single center retrospective non randomized study, although patients were followed up for longer period. We have presented follow-up data up to one year in the study.

CONCLUSION:
Results of our study showed that novel biodegradable polymeric technology for paclitaxel-eluting stent was associated with very low event rates and there was no evidence of late thrombosis till one-year follow-up in real-world patients with coronary artery disease.

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