Five-year clinical follow-up of the STENTYS self-apposing stent in complex coronary anatomy: a single-centre experience with report of specific angiographic indications

All consecutive patients treated with the STENTYS stent since the introduction of the device in our centre from April 2010 until January 2016 were evaluated for this registry. Patients were excluded if they presented with ST-segment elevation myocardial infarction (STEMI) or were enrolled in a randomised trial. All other clinical indications for percutaneous coronary intervention were allowed. Percutaneous coronary intervention involving the STENTYS device was in the setting of routine clinical care. The choice for a drug-eluting stent or bare-metal stent (BMS) was at the discretion of the operator. Pre-implantation sizing was done by visual estimation. All patients provided written informed consent for this registry. All patients were pre-loaded with aspirin and a P2Y12 inhibitor, if not already on chronic therapy. Patients received 5,000 IU of unfractionated heparin at the start of the procedure. The use of peri-procedural glycoprotein IIb/IIIa receptor inhibitors was left at the discretion of the operator.

The STENTYS stent is a new generation self-expanding device, made of a nitinol platform, a biocompatible nickel and titanium alloy. The stent is 6 French-compatible and is delivered using a rapid-exchange delivery system over a conventional 0.014″ guidewire. It is available in 3 lengths (17 mm, 22 mm and 27 mm), and in three diameter sizes: small (2.5–3.0 mm), medium (3.0–3.5 mm), and large (3.5–4.5 mm). The strut thickness is 102 microns (small size) or 133 microns (medium and large sizes). The large STENTYS can expand over 6.0 mm suitable for absolute vessel diameters of >4.5 mm. The stent is available as bare-metal stent and drug-eluting stent (paclitaxel or sirolimus). Since apposition is possible in large and variable vessel diameters of, for example, proximal and distal main branches, the stent can be used safely and effectively in bifurcation lesions [7‐9] and in saphenous vein grafts [10]. Moreover, the nitinol platform can enlarge further after implantation. Therefore, the STENTYS device is extensively evaluated in patients with acute myocardial infarction in the APPOSITION trials [5, 11‐13], which revealed lower rates of strut mal-apposition as compared with balloon-expandable stents and favourable clinical results. During the present study, the novel balloon-based delivery system Xposition was not yet available for commercial use.

An experienced interventional cardiologist (KTK) retrospectively reviewed the procedural report and procedural angiograms of all lesions treated with STENTYS to obtain lesion characteristics and to access the angiographic indication for this device if it was not stated in the report. The following angiographic indications were specified; aneurysm; ectasias; tapering; absolute reference vessel diameter 4.0–5.0 mm, bifurcation lesions and lesions located in saphenous vein grafts. Aneurysm was defined as localised or segmental dilatation which exceeds the diameter of normal adjacent segments by 1.5 times [14]. Ectasia was defined as irregular diffuse dilatation (>1.5 times the normal diameter) that involves more than one third of the length of the coronary artery [15, 16]. Tapering was defined as a significant diameter change of ≥1 mm from the proximal to the distal vessel segment. Offline quantitative coronary angiography (QCA) analyses were performed using dedicated software (QAngioXA version 7.3; Medis, Leiden, the Netherlands). Standardised QCA methodology was used including a bifurcation algorithm for bifurcation lesions. Pre- and post-procedural reference vessel diameter, minimal luminal diameter and percentage diameter stenosis (%DS) were obtained. Pre-implantation D‑max is obtained to assess maximal luminal diameters at baseline. Acute gain was defined as the difference between pre-procedural and post-procedural minimal luminal diameter. Longitudinal geographic mismatch on QCA was defined as the entire length of the lesion (as defined by QCA) not completely covered by the stent. Angiographic success was defined as final residual stenosis of less than 20% by offline QCA and thrombolysis in myocardial infarction (TIMI) 3 flow on the final angiogram without geographic mismatch.

Patients were contacted individually to obtain follow-up data. Hospital records and coronary angiograms were reviewed to complete information. Reported clinical outcomes included cardiac death, target vessel myocardial infarction (TV-MI), non-TV-MI, clinically indicated target lesion revascularisation, target vessel revascularisation (TVR), non-TVR, and definite/probable stent thrombosis according to the Academic Research Consortium definitions [17]. Target vessel failure was defined as the composite of cardiac death, TV-MI or TVR. Procedural success was defined as angiographic success without in-hospital target vessel failure.

Continuous variables were presented as mean ± standard deviation, categorical variables as frequencies. We performed comparisons of variables using the two-sided Student-t test, chi-square or Fisher’s exact test, as appropriate. Event rates were assessed by Kaplan-Meier estimates and compared with the log-rank test. Follow-up was censored at 5 years or at the last known date of follow-up, whichever came first. We used the SPSS software package (version 24, IBM, Chicago, IL, USA).

Between April 2010 and January 2016, 120 patients were included in our registry including 19 STENTYS bare-metal stents, and 101 STENTYS drug-eluting stents. We report the outcome separately. Baseline clinical characteristics are summarised in Table 1 of the online supplementary material. Mean age was 65 ± 12 years in the group with a drug-eluting stents vs. 67 ± 13 in the group with a bare-metal stent. In the group with a drug-eluting stent, 46% of patients had stable angina, 16% unstable angina and 39% non-ST-segment elevation myocardial infarction (NSTEMI). In the group with a bare-metal stent, 53% of patients had stable angina, 26% unstable angina and 21% NSTEMI.

Lesion and procedural characteristics are shown in Table 2 of the online supplementary material. A total of 124 lesions were treated (study lesions). Of this total, 104 lesions were treated with the STENTYS drug-eluting stent and 20 with the STENTYS bare-metal stent. D‑max was 4.51 ± 0.99 mm in the group with a drug-eluting stent and 4.63 ± 1.05 mm in the group with a bare-metal stent (p = 0.64). A considerable number of patients had a pre-implantation D‑max of ≥4.0 to ≤5.0 mm (38% vs. 37% respectively, p = 0.95). In both groups, there was even a pre-implantation D‑max of ≥5.0 mm in approximately one third of cases (28% vs. 37% respectively, p = 0.42). Geographic mismatch occurred in 2% in the group with a drug-eluting stent vs. 5% in the group with a bare-metal stent (p = 0.46). Angiographic success was 69% in the group with a drug-eluting stent vs. 68% in the group with a bare-metal stent (p = 0.94), similar to the procedural success due to no in-hospital target vessel failure.

Angiographic indications for operators to choose the STENTYS stent, were aneurysm (30%), ectasia (19%), tapering (27%), bifurcation lesions (8%), saphenous vein graft lesions (16%) and absolute target vessel diameters (22%) (Tab. 1). More than 1 angiographic indication could apply, for example, tapering and absolute target vessel diameter (Fig. 2). QCA results are summarised in Tab. 2. Reference vessel diameter, %DS and the minimal luminal diameter of all angiographic indications are shown separately illustrating the angiographic differences between the groups. In tapering, the reference vessel diameter of the proximal edge is remarkably larger than the reference vessel diameter in the distal edge of the treated segment. Angiographic outcomes for the bifurcation lesions are shown in Table 3 of the online supplementary material.

Clinical follow-up was obtained for all patients with a median follow-up of 51 months (IQR 42–60). One patient was lost to follow-up due to emigration to Suriname 2 years after baseline percutaneous coronary intervention and is censored from the date of emigration. Target vessel failure was observed in 25 patients (24.1%), 19 (22.8%) in the group with a drug-eluting stent vs. 6 (33%) in the group with a bare-metal stent (Tab. 3). Landmark analysis at 2‑year up to 5‑year follow-up revealed an incremental target vessel failure rate of 13.3% in the group with a drug-eluting stent and 15.2% in the group with a bare-metal stent (p = 0.73) (Fig. 3). In the total cohort, definite stent thrombosis occurred in 4 cases (3.8%). Stent thrombosis characteristics are shown in Table 4 of the online supplementary material. Individual clinical endpoints are shown in Tab. 3 and Fig. 4. Clinical outcomes per angiographic indication are shown in Table 5 of the online supplementary material. Comparison between the bare-metal stent group and the drug-eluting stent group should be interpreted with caution due to the non-randomised design and the small sample size.

Several theoretic advantages of the nitinol self-apposing platform were previously evaluated in selected cohorts. Naber et al. observed a definite stent thrombosis rate of 1% at 6‑month and 0% at 12-month follow-up in bifurcation lesions [7]. A large STEMI registry with STENTYS bare-metal stent and paclitaxel-eluting stent (PES) revealed definite stent thrombosis rates of 3.3% at 2‑year follow-up [13]. Less data is available for the stent performance in all-comer populations. An evaluation of a small real-world cohort reveals that interventionalists chose the STENTYS device in a comparable selection of angiographic situations, including bifurcation lesions, acute coronary syndrome and ectatic coronaries, with a stent thrombosis rate of 2.5% at 21 ± 13 months [18]. Another real-world single-centre experience with both STENTYS bare-metal stent and paclitaxel-eluting stent from Italy reported a stent thrombosis rate of 1.8% at 23.6 ± 12.6 months [19]. A larger multicentre cohort reported stent thrombosis rates of 2.6% at 2.5 years in all-comer patients, based on usage of STENTYS bare-metal stent, paclitaxel-eluting stent and sirolimus-eluting stent [20]. In the present study, we observed a geographic mismatch in 2% in the group with a drug-eluting stent and 5% in the group with a bare-metal stent (p = 0.46), and overall stent thrombosis rate of 3.8% at 5‑year follow-up. Considering the complexity of our cohort including both STENTYS bare-metal stent and paclitaxel-eluting stent, these indicators for device performance are acceptable. The low angiographic success rates of 69% in the group with a drug-eluting stent and 68% in the group with a bare-metal stent is partly explained by the fact the we incorporated a geographic mismatch and measured the residual stenosis on off-line QCA. These success rates should be interpreted with caution since QCA analyses might overestimate residual stenosis in aneurysmatic and ectatic lesions.

It is well-known that complex target lesion anatomy is associated with an increased risk of adverse outcome [21, 22]. Using the SYNTAX score, an angiographic scoring system quantifying the complexity of coronary artery disease, it is possible to identify high-risk patients based on angiographic characteristics [23, 24]. Unprotected left main, multi-vessel disease, longer lesions, bifurcation or trifurcation lesions and large thrombus load are incorporated and considered more complex. A recent pooled analysis evaluating new-generation balloon-expandable drug-eluting stents, including stents eluting everolimus and zotarolimus, and biodegradable polymer stents eluting biolimus and sirolimus, demonstrated a definite stent thrombosis rate of 1.0% at 2‑year follow-up in patients with a higher coronary complexity (SYNTAX score > 11) [25]. The RESOLUTE all-comers trial comparing the Resolute zotarolimus-eluting stent with the Xience V everolimus-eluting stent revealed definite stent thrombosis rates of 1.2% vs. 0.4% (p = 0.14) respectively in a pre-specified subgroup of complex patients at 1‑year follow-up [26]. The same trial reported definite stent thrombosis rates of 1.6% vs. 0.8% (p = 0.08) respectively at 5‑year follow-up in an all-comers population [27]. Our observations of much higher stent thrombosis rates could partially be explained by the atypical complexities including aneurysms, ectasia and large tapering. Moreover, the patients were treated with the STENTYS bare-metal stent or paclitaxel-eluting stent delivered with the conventional delivery system. The Xposition delivery system with the sirolimus-eluting STENTYS device, where precise stent delivery is made possible by a delivery balloon which is retracted after stent delivery, might improve clinical outcome in complex coronary anatomy [28].

This study is limited by its observational design. It is a small, single-centre cohort study of complex lesions. A matched control group with such atypical anatomical high-risk lesions treated with balloon-expandable stents was not available. The STENTYS use, including the choice for STENTYS drug-eluting stent or bare-metal stent was at the discretion of the operator. The angiograms were reviewed by a single expert only. No routine angiographic follow-up was performed in these patients. Finally, clinical outcomes were not adjudicated by an independent clinical endpoint committee.