Biodegradable Polymer-Coated Sirolimus- Eluting Stent Implantation in AMI A Clinical and Angiographic Study General Hospital of Chinese People’s Armed Police Forces Huiliang Liu Shengli Yang

A Subgroup of CREATE (Multi-Center Registry of Excel Biodegradable Polymer Drug-Eluting Stents)

Investigators: Huiliang Liu, Shengli Yang: General Hospital of Chinese People’s Armed Police Forces, Beijing, China; Yaling Han: Shenyang Northern Hospital, Shenyang, China; Bo Xu, Runlin Gao: Cardiovascular Institute and Fuwai Hospital, Beijing, China; Lixia Yang: Kunming General Hospital of Chengdu Military Region, Kunming, China; Xiaoming Shang: Tangshan Gongren Hospital, Tangshan, China; Tieming Jiang: Affiliated Hospital of Chinese People's Armed Police Forces Medical College, Tianjin, China; Zhanquan Li: The People's Hospital of Liaoning Province, Shenyang, China; Hua Zhang: Shaanxi Provincial Corps Hospital of Chinese People's Armed Police Forces, Xi'an, China; Hui Li: Daqing Oilfields General Hospital, Daqing, China; Jian Qiu: Guangzhou Army General Hospital, Guangzhou, China; Yingfeng Liu: Zhujiang Hospital of Southern Medical University, Guangzhou, China;

Background Coronary heart disease is a leading cause of death around the world. The development of drug-eluting stents has dramatically lowered the risk of in-stent restenosis compared to bare metal stents. Clinicians in the “real word” have begun utilizing DES in the setting of AMI despite the fact that no practice guidelines exist to support their use.

Lingering concerns exist about the reported increased risk of early and late stent thrombosis after DES implantation. Routine stent implantation has been shown to have a better procedural success rate and clinical outcome than balloon angioplasty in patients presenting with acute myocardial infarction (AMI).

However, in-stent restenosis and vessel reocclusion remain significant clinical problems limiting the long-term success of percutaneous treatment. Sirolimus-eluting stents (SES) and biodegradable polymer-coated sirolimus-eluting stents (Excel, JW Medical System, Weihai, China) have recently been proven to reduce restenosis and reintervention compared with bare stents.

Safety and effectiveness of Excel in acute myocardial infarction remain unknown.

Objectives The present study sought to evaluate the safety and effectiveness of Excel in acute myocardial infarction with 6-month dual antiplatelet therapy in daily practice.

Methods and Results Since June 01, 2006, a policy of routine Excel stents implantation has been instituted in 59 centers from 4 countries, with no clinical or anatomic restrictions, as part of the CREATE (Multi-Center Registry of Excel Biodegradable Polymer Drug-Eluting Stents) registry. Recommended antiplatelet regimen included clopidogrel and aspirin for 6 months followed by chronic aspirin therapy. During 6 months of enrollment, 760 patients with acute myocardial infarction underwent percutaneous recanalization and Excel stents implantation; these patients comprise the study population.

Weight-adjusted heparin was administered to achieve an activated clotting time of >300 seconds, or 200 to 250 seconds when platelet glycoprotein IIb/IIIa inhibitor was used. The local ethics committee approved the study protocol, and informed consent was obtained from all patients. Information regarding repeat interventions was prospectively collected in the local database. Survival status was assessed by written or telephone inquiries. Questionnaires to assess clinical status were sent to all living patients.

The incidence of major adverse cardiac events (death, nonfatal myocardial infarction, reintervention) was evaluated. Six-month angiographic follow-up was scheduled per protocol. At baseline, 152 patients (20.0%) had diabetes mellitus, 27 (3.6%) had had a previous myocardial infarction. 649 (89.7%) presented B/C type disease, and 172(22.6%) presented multivessel disease. No. of target vessels were located in the left main(LM) in 5 cases (0.5%), the left anterior descending (LAD) in 507 (48.7%), the left circumflex (LCX) in 187 (17.9%), and the right coronary (RCA) 343 (32.9%).

Table 1. Baseline Clinical Characteristics of the 2 Groups MI Group （ n=760 ） Non-MI Group （ n=1317 ） All （ n=2077 ） χ 2 or t test P value Male sex (%)596 （ 78.4% ） 932 （ 70.8% ） 1528 （ 73.4% ） ＜ Age (years)59.1 ± ± ± ＜ Smoking426 （ 56.0% ） 615 （ 46.7% ） 1041(50.1%) ＜ HTN361 （ 47.5% ） 796 （ 60.4% ） 1157 （ 55.7% ） ＜ Dyslipidemia107 （ 14.1% ） 258 （ 19.6% ） 365(17.8%) Diabetes152 （ 20.0% ） 288 （ 21.9% ） 440 （ 21.2% ） history of OMI27(3.6%)207(15.8%)234 （ 11.3% ） ＜ Family history of CAD 50(6.6%)108(8.2%)158 （ 7.6% ） history of stroke113(14.9%)243(18.5%)356 （ 17.1% ） Diagnosis AMI with 24h386(18.6%)0 Recent MI374(18.0%)0 Unstable angina 01105(53.2%) Stable angina0131(6.3%) Silent ischemia 081(3.9%)

Overall, 1082 target lesions were identified. The target lesions were A type in 111 cases (10.3%), B1 in 201 (18.6%), B2 in 252 (23.3%), and C in 518 (47.9%). Complete follow-up was available for 99.3% of the patients at 180 days, 99.1% at 360 days, and 99.1% at 540 days. A total of 17 deaths occurred during the 180 days (2.3%), 25 deaths occurred during the 360 days, and 27 deaths occurred during the 540 days.

Table 2. Angiographic and Procedural Characteristics MI Group （ n=760 ） Non-MI Group （ n=1317 ） All （ n=2077 ） χ 2 or t test P value No. of target vessels LM5(0.5%)21(1.1%)26(0.9%) LAD507(48.7%)916(49.0%)1423(48.9%) LCX187(17.9%)377(20.2%)564(19.4%) RCA343(32.9%)556(29.7%)899(30.9%) MVD172(22.6%)386(29.3%)558(26.9%) ＜0.001 No. of target lesions ＜0.001 A111(10.3%)287(14.4%) 398 （ 12.9% ） B1201(18.6%)432(21.6%) 633 （ 20.6% ） B2252(23.3%)475(23.8%) 727 （ 23.6% ） C518(47.9%)804(40.2%) 1322(42.9% ） No. of stents per patient 1.70 ± ± ± ＜0.001 Stenosis before procedural （ % ） 91.5± ± ± ＜0.001 Average reference vessel diameter, mm 3.00± ± ± Minimal luminal diameter, mm 0.39± ± ± ＜0.001 Average lesion length, mm 22.36± ± ± Average stent diameter, mm 3.24± ± ＜0.001 Average stent length, mm 22.5± ± ± Residual stenosis0.80± ± ±

The average duration of clopidogrel treatment was 180 days. The cumulative rates of major adverse cardiac events were 2.0% at 180 days, 3.9% at 1 year, and 4.2% at 18 months. Overall rate of stent thrombosis was 0.66% at 18 months. The rates of acute, subacute, late, and very late stent thrombosis were 0%(0), 0.39%(3), 0.26%(2), and 0%(0), respectively. Angiographic follow-up, performed in 342 (33.4%) lesions from 272 patients (35.8%), revealed a mean in- stent late lumen loss of 0.20 ± 0.41 mm. Binary restenosis rates were 3.5% in-stent and 6.2% in- segment.

Table 3. Clinical Outcomes(1) EventsMI Group （ n=760 ） Non-MI Group （ n=1317 ） All （ n=2077 ） χ 2 or t test P value 6-month outcomes （ n=2068 ） Death17 （ 2.3% ） 7 （ 0.5% ） 24 （ 1.2% ） ＜ Cardiac12 （ 1.6% ） 6 （ 0.5% ） 18 （ 0.9% ） Noncardiac5 （ 0.7% ） 1 （ 0.2% ） 6 （ 0.3% ） Nonfatal MI2 （ 0.3% ） 5 （ 0.4% ） 7 （ 0.3% ） TLR3 （ 0.4% ） 5 （ 0.4% ） 8 （ 0.4% ） MACE15 （ 2.0% ） 13 （ 1.0% ） 28 （ 1.3% ） No. of missing549 Rate of following up 755/760 (99.3%) 1313/1317 (99.7%) 2068/2077 (99.6%)

Table 3. Clinical Outcomes(2) EventsMI Group （ n=760 ） Non-MI Group （ n=1317 ） All （ n=2077 ） χ 2 or t test P value 12-month outcomes （ n=2063 ） Death25 （ 3.3% ） 10 （ 0.8% ） 35 （ 1.7% ） ＜ Cardiac14 （ 1.9% ） 8 （ 0.6% ） 22 （ 1.1% ） Noncardiac11 （ 1.5% ） 2 （ 0.2% ） 13 （ 0.6% ） ＜ Nonfatal MI3 （ 0.4% ） 5 （ 0.4% ） 8 （ 0.4% ） TLR15 （ 2.0% ） 17 （ 1.3% ） 32 （ 1.6% ） MACE29 （ 3.9% ） 27 （ 2.1% ） 56 （ 2.7% ） No. of missing7714 Rate of following up 753/760 (99.1%) 1310/1317 (99.5%) 2063/2077 (99.3%)

Table 3. Clinical Outcomes(3) EventsMI Group （ n=760 ） Non-MI Group （ n=1317 ） All （ n=2077 ） χ 2 or t test P value 18-month outcomes （ n=2062 ） Death27 （ 3.6% ） 12 （ 0.9% ） 39 （ 1.9% ） ＜ Cardiac15 （ 1.1% ） 8 （ 0.6% ） 23 （ 1.1% ） Noncardiac11 （ 0.7% ） 5 （ 0.4% ） 16 （ 0.8% ） Nonfatal MI3 （ 0.5% ） 6 （ 0.5% ） 9 （ 0.4% ） TLR17 （ 2.3% ） 22 （ 1.7% ） 39 （ 1.9% ） MACE32 （ 4.2% ） 32 （ 1.7% ） 64 （ 3.1% ） No. of missing7815 Rate of following up 753/760 (99.1%) 1309/1317 (99.4%) 2062/2077 (99.3%)

Table 4. The thrombosis events by ARC definition at 18-months MI group （ n=760 ） Non-MI group （ n=1317 ） All （ n=2062 ） P Definition257 Probable235 Possible156 Total5 （ 0.66% ） 13 （ 0.99% ） 18 （ 0.87% ） 0.741

Discussion The present study is the first report on Excel biodegradable polymer-based sirolimus-eluting stent implantation for patients with AMI. The main finding is that, in these patients, Excel biodegradable polymer-based sirolimus-eluting stent implantation appears highly effective in preventing neointimal proliferation and restenosis, with results similar to those observed in a randomized trial for relatively simple lesions Primary percutaneous coronary intervention has been demonstrated to be more effective than thrombolytic therapy for the treatment of AMI.

In the Stent PAMI (Stent Primary Angioplasty for Myocardial Infarction) trial, 6-month restenosis and target vessel revascularization rates were 20.3% and 7.7%, respectively In the CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications) trial, the corresponding values were 22.2% and 8.9%, and reocclusion of the infarct-related artery 5.7% Lee RL, et al. recently demonstrated the clinical safety of drug-eluting stents in the Korea (Acute Myocardial Infarction Registry), although AMI at presentation was still associated with an increased risk of adverse events at followup.

The present study, with the low event rate and the low episodes of acute and subacute thrombosis, confirms the safety of Excel biodegradable polymer-based sirolimus-eluting stent utilization in patients with AMI. In this prospective, multi-center registry of Excel biodegradable polymer-based sirolimus-eluting stent implantation in AMI, all the limitations inherent to this particular study design apply, and the angiographic follow up patient numbers ware relatively small.

Conclusions Routine Excel biodegradable polymer-based sirolimus-eluting stent implantation during mechanical reperfusion of AMI is safe and effective and associated with low MACE at 6, 12, and 18 months. Larger studies are necessary to confirm these findings and to evaluate the impact of Excel biodegradable polymer-based sirolimus-eluting stent implantation on clinical events for patients with AMI.

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