Two Years Follow-Up Outcome of Synergy™ Coronary Stent: Comparison between Case Control Study-Oriented Definition/Criterion and Real-World Results

Research Article

Austin J Clin Cardiolog 2023; 9(1): 1102.

Two Years Follow-Up Outcome of Synergy™ Coronary Stent: Comparison between Case Control Study-Oriented Definition/Criterion and Real-World Results

Sugie T, Kotani J, Kashima YD, Tadano Y*, Watanabe T, Hachinohe D, Kaneko U, Kobayashi K, Kanno D and Fujita T

Asia Medical Group, Sapporo Cardiovascular Clinic, Japan

*Corresponding author: Yutaka Tadono Sapporo Cardiovascular Clinic, North 49th Av., East 16th St., 8-1, Higashi ward, Sapporo, Hokkaido, Japan

Received: November 24, 2022; Accepted: December 28, 2022; Published: January 03, 2023

Abstract

Objectives: To clarify the 2 years outcome of Bioabsorbable Polymer Everolimus-Eluting Stent (BP-EES) using several criteria/definitions. Previous reports have showed worse outcomes in Real-World (RW) setting than case-Controlled Clinical trials (CC).

Methods and Materials: We studied consecutive patients who received BP-EES implantation from October 2017 through January 2018. We adopted the parameters used in previous BP-EES associated CC (SYNERGY, EVOLVE), compared the CC inclusion criteria (on-label) with others (offlabel) at 2 years follow-up.

Results: There were 678 BP-EESs inserted in 437 patients (283 male, mean age 72.3±11.2 years). Data from 4 patients lacked, and therefore the follow-up rate was 99.1%. There were 381 patients (87.2%) satisfying the CC criteria. Male gender, ejection fraction <40%, smoker, multiple stenting, total stent length, target vessel failure and all death was higher in the off-label group (P<0.05). Regarding revascularization- related parameters (all target lesion/non-target lesion revascularization), there was no difference between the 2 groups (TLR 6.1% vs 3.6%, non-TL TVR 5.6% vs 10.9%; CC vs off-label, p=ns, respectively). On the other hand, comparison of TLR using the CC definition (ischemia-oriented TLR) and real-world definition (any TLR) showed approximately 2-3 times higher frequency in the real-world basis (1.6% vs 5.8% per patient basis and 2.1%vs 5.8% per stent basis).

Conclusions: Different definitions for repeat angioplasty among the reports may be a key cause of the discrepancy in revascularization frequency in dug-eluting stent studies, and it is the different inclusion criteria among studies that are associated with patient vulnerability.

Introduction

Bioabsorbable polymer technology aims to reduce potential polymer-related adverse events and recent studies (both randomized and observational) of bioabsorbable polymer Drug- Eluting Stent (DES) have shown supporting outcomes [1-3]. The SYNERGY stent (Boston Scientific Corporation, Marlborough, MA) is a thin-strut (74–81 μm) Platinum Chromium (PtCr) metalalloy stent that elutes everolimus from thin bioabsorbable poly (DL- lactide-co-glycolide) polymer applied to the abluminal surface. The polymer is absorbed shortly after the drug elution is complete at 3 months, providing optimal healing and freedom from long-term polymer exposure within the vessels [4,5].

In the landmark study EVOLVE, SYNERGY demonstrated comparable outcomes to durable polymer PROMUS Element Plus, with low rates of stent thrombosis and adverse events through 5 years of follow-up [6]. However, the clinical data from real-world cases differ from trial-based studies because these pivotal studies have exclusion criteria, and only examine the data which met their strict definitions [2-7].

The aim of this study was to assess the 2-year clinical outcomes with high follow-up rate of bioabsorbable polymer everolimus-eluting stent (BP-EES) using several criteria/definitions.

Methods

Study Design and Definitions

This study was based on a single-center, retrospective, all-comer patients’ registry of Sapporo Cardiovascular Clinic (SCVC), designed to reflect the “real-world” practice. We studied all patients who received PCI using BP-EES from October 2017 through January 2018. In reflecting the real-world data, we analyzed overall results similar to previous case-control studies, and added the comparison of label indication; that is, case-control study inclusion criteria (on-label) versus others (off-label) to enhance the differences between the real-world and case control studies.

Procedure

As per routine, both pre- and post-dilatations were mandated, and intracoronary imaging device-assisted angioplasty was performed. Debulking devices, such as at hero ablation, were used by the operator’s decision. Staged procedures with allocated stents were permitted within 3 months after the initial percutaneous intervention with coronary stenting. Dual Anti- Platelet Therapy (DAPT) of aspirin (81mg throughout their lifespan) and clopidogrel (75mg feed for at least 1 year from index procedure) was recommended, its duration ultimately being left to the discretion of the attending physicians. Generally, DAPT was prescribed for a lifetime. Laboratory tests included systematic assessment of post-intervention cardiac markers mandatory for all patients, and subsequent serial measurements in case of suspected ischemia. PCI-associated MI was adopted from universal definition of myocardial infarction. (type 4a MI) [8].

Baseline characteristics, history of cardiovascular disease, coronary risk factors, medications, and procedural data were obtained and recorded by the physicians and research associates of the Cardiovascular-Institute of Therapeutic Evaluation and Creation (CiTEC). Follow-up data were obtained through a chart review and lacking information was collected via telephone interview or from referring physicians. Although angiographic follow-up assessment was not mandatory, coronary Computed Tomography (CT) angiography follow-up evaluations were basically recommended at 6, 12 and 24 months after PCI in SCVC.

Definitions and Outcomes

Basic outcomes followed the pivotal BP-EES trial (EVOLVEII) and consensus document of the standardized definition for clinical research [5,6,8]. Briefly, rate of Target Lesion Failure (TLF) was defined as a composite of any ischemia-driven revascularization of the target lesion, Myocardial Infarction (MI) related to the target vessel or any cardiac death from discharge to 24 months follow-up. Individual components were further presented as follows: repeat treatment to the inside of the implanted stent or within 5 mm proximal/distal to the stent was defined as Target Lesion Revascularization (TLR), but when done elsewhere within the target vessel it was recorded as nontarget lesion revascularization (non-TL TVR). At least receiving revascularization anywhere during follow-up period is defined as any revascularization. To reflect real-world data, we listed not only ischemia-driven revascularization (i.e., case-control study definition) but also other all events separately (clinically driven revascularization). In this study, ischemia-driven revascularization only indicated fractional flow reserve positive (≤0.8) or presenting ischemic sign during diagnosis, e.g., chest pain, electrocardiogram abnormalities). Deaths were classified as cardiac, non-cardiac and unidentified. Uncertain-cause death including sudden death was included into cardiac death incomposite analysis. MI was defined on the basis of ECG changes and rise in creatine kinase enzyme concentration above three times the upper normal limit. Stent thrombosis was also classified based on Standardization of clinical trials defined by the Academic Research Consortium (ARC) [7]. Both cerebral infarction and hemorrhagic strokes were noted. Off-label indication included the lesion and strategy subsets that were eliminated from pivotal BP-EES studies [4-6]: briefly,>4 lesions within a vessel, triple-vessel disease, ST-segment-elevation myocardial infarction, stenting for Left Main Trunk (LMT) or saphenous vein graft lesions, chronic total occlusion, in-stent restenosis, and bifurcations requiring ≤2 stents. Multiple stenting was defined as requiring ≥2 stents in the target vessel within a procedure.

Statistical Analysis and Ethics

All analyses were performed using R version 4.0.2. [9] Continuous variables are presented as mean ± standard deviation. Continuous variables were compared using the Student’s t-test. Categorical variables were compared using the chi-square test or Fisher’s exact test. The threshold for significance was p<0.05. The study was approved by the institutional review board, and written informed consent was obtained from all patients. SCVC belongs to the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) and participates in J-PCI registry, and therefore the study/procedure basically followed their definitions/ recommendations [10].

Results

Patient Flow and Background

The patient flow of this study is shown in (Figure 1). From October 2017 through January 2018, 437 patients (282 males, 64.5%) were enrolled and analyzed. Baseline patient demographics were as follows: diabetic mellitus 28.4% (124/437), hypertension 78.5% (343/437), dyslipidemia 83.5% (365/437), smoker 20.4% (89/437) and hemodialysis 4.1% (18/437). The history of myocardial infarction and aorto-coronary bypass surgery were 22.7% (99/437) and 5.0% (22/437), respectively.