Original Contribution

One-Year Clinical Outcomes of Patients Presenting With ST-Segment Elevation Myocardial Infarction Caused by Bifurcation Culprit Lesions Treated With the Stentys Self-Apposing Coronary Stent: Results From the APPOSITION III Study

Maik J. Grundeken, MD, PhD1;  Huangling Lu, MD1;  Nicola Vos, MD2;  Alexander IJsselmuiden, MD, PhD3;  Robert-Jan van Geuns, MD, PhD4;  Rainer Wessely, MD, PhD5;  Thomas Dengler, MD6;  Alessio La Manna, MD7;  Johanne Silvain, MD, PhD8;  Gilles Montalescot, MD, PhD8;  Ren√© Spaargaren, MD8;  Jan G.P. Tijssen, PhD1;  Robbert J. de Winter, MD, PhD1;  Joanna J. Wykrzykowska, MD, PhD1;  Giovanni Amoroso, MD, PhD2;  Karel T. Koch, MD, PhD1

Maik J. Grundeken, MD, PhD1;  Huangling Lu, MD1;  Nicola Vos, MD2;  Alexander IJsselmuiden, MD, PhD3;  Robert-Jan van Geuns, MD, PhD4;  Rainer Wessely, MD, PhD5;  Thomas Dengler, MD6;  Alessio La Manna, MD7;  Johanne Silvain, MD, PhD8;  Gilles Montalescot, MD, PhD8;  Ren√© Spaargaren, MD8;  Jan G.P. Tijssen, PhD1;  Robbert J. de Winter, MD, PhD1;  Joanna J. Wykrzykowska, MD, PhD1;  Giovanni Amoroso, MD, PhD2;  Karel T. Koch, MD, PhD1

Abstract: Objective. To investigate outcomes in patients with ST-segment elevation myocardial infarction (STEMI) after treatment with the Stentys self-apposing stent (Stentys SAS; Stentys S.A.) for bifurcation culprit lesions. Background. The nitinol, self-expanding Stentys was initially developed as a dedicated bifurcation stent. The stent facilitates a provisional strategy by accommodating its diameter to both the proximal and distal reference diameters and offering an opportunity to “disconnect” the interconnectors, opening the stent toward the side branch. Methods. The APPOSITION (a post-market registry to assess the Stentys self-expanding coronary stent in acute myocardial infarction) III study was a prospective, multicenter, international, observational study including STEMI patients undergoing primary percutaneous coronary intervention (PCI) with the Stentys SAS. Clinical endpoints were evaluated and stratified by bifurcation vs non-bifurcation culprit lesions. Results. From 965 patients included, a total of 123 (13%) were documented as having a bifurcation lesion. Target-vessel revascularization (TVR) rates were higher in the bifurcation subgroup (16.4% vs 10.0%; P=.04). Although not statistically significant, other endpoints were numerically higher in the bifurcation subgroup: major adverse cardiac events (MACE; 12.7% vs 8.8%), myocardial infarction (MI; 3.4% vs 1.8%), and definite/probable stent thrombosis (ST; 5.8% vs 3.1%). However, when postdilation was performed, clinical endpoints were similar between bifurcation and non-bifurcation lesions: MACE (8.7% vs 8.4%), MI (1.2% vs 0.7%), and definite/probable ST (3.7% vs 2.4%). Conclusions. The use of the Stentys SAS was safe and feasible for the treatment of bifurcation lesions in the setting of primary PCI for STEMI treatment with acceptable 1-year cardiovascular event rates, which improved when postdilation was performed.

J INVASIVE CARDIOL 2017;29(8):253-258.

Key words: bifurcation, Stentys, STEMI, postdilation, self-expanding stent, self-apposing stent


Percutaneous coronary intervention (PCI) of coronary bifurcation lesions is considered to be technically challenging.1 The Stentys self-apposing stent (SAS; Stentys S.A.) is a self-expanding nitinol stent that was initially developed as a dedicated bifurcation stent.2-4 The stent facilitates the provisional strategy, which is the preferred strategy based on multiple randomized trials,5-7 by accommodating both the distal and proximal reference diameters and providing the opportunity to “disconnect” the interconnecting links between the crowns, opening the stent by flaring the stent into the side branch.3 Stentys implantation for the treatment of bifurcation lesions has been investigated  in the OPEN I and OPEN II registry studies, including a total of 270 patients.2,3,8 

Soon after its introduction as a dedicated bifurcation stent, Stentys was also clinically investigated in patients presenting with ST-segment elevation myocardial infarction (STEMI).9-11 The potential benefit for STEMI patients is that the stent adapts itself to the vessel wall12 and expands further during the days following primary PCI, when vessel-wall relaxation occurs after the vasoconstriction of the acute phase. Previous randomized trials have shown superior apposition of the Stentys SAS compared with balloon-expandable stents immediately post procedure, at 3 days post procedure, and at 4-month follow-up.11,13 

The APPOSITION III (A Post-market registry to Assess the Stentys Self-Expanding Coronary Stent in Acute Myocardial Infarction) was a multicenter, observational study including nearly 1000 STEMI patients to evaluate the safety and performance of the use of Stentys SAS in the setting of primary PCI.10 One-year clinical follow-up in this study showed acceptable results.10 The current study investigates clinical outcomes in STEMI patients included in the APPOSITION III study who were treated for a bifurcation culprit lesion.

Methods 

The APPOSITION III study has been discussed in detail elsewhere.10,14 In short, it was a prospective, multicenter (51 centers), international (14 countries), observational study. Patients with STEMI undergoing primary PCI caused by a de novo culprit lesion were eligible for inclusion. 

Stentys deployment is performed by withdrawing a retractable sheath using a thumb slider on the handle. The stent is positioned using two markers on the delivery system, indicating the proximal and distal ends of the stent. There is a third marker on the distal end of the outer sheath so that its retraction can be visualized under fluoroscopy (Figure 1). The more recently developed Stentys Xposition S delivery system was not used in this study.14 Two Stentys SAS types were available: a bare-metal stent (BMS) version and a paclitaxel drug-eluting stent (DES) version. The use of the BMS or DES version was according to operator’s preference in the setting of routine clinical care performing primary PCI. Postdilation was initially left to operator’s discretion, but became strongly recommended after an interim analysis showed a higher event rate in patients in whom postdilation was not performed.10 Disconnection of the interconnecting links, in case the SAS was placed over a side branch (Figure 2), was left to the operator’s preference. A case example is shown in Figure 3. Stentys SAS was CE marked and available for routine clinical use in participating centers. Written informed consent was obtained from each patient before inclusion in the registry and the study protocol was approved by the local ethics committees.

The primary endpoint was defined as 1-year major adverse cardiac event (MACE; defined as the composite of cardiac death, recurrent target-vessel [TV] myocardial infarction [MI], and clinically driven target-lesion revascularization [TLR]). Secondary endpoints included all-cause death, cardiac death, TV-MI, any MI, clinically driven TLR, any target-vessel revascularization (TVR), definite stent thrombosis (ST), probable ST, and the combined endpoint of definite/probable ST. All events were independently adjudicated by a clinical event committee. Every culprit lesion was documented by the study sites as being a bifurcation (ie, involving a side branch >2.25 mm) or not by a “thick box” in the electronic case report form (eCRF). Statistical analyses were performed using the SPSS software package v. 20.0 (IBM). 

Results 

From the 965 patients included in the APPOSITION III registry, a total of 123 (13%) were documented by the study sites as bifurcation culprit lesions. There were no differences between the bifurcation subgroup and the non-bifurcation subgroup in demographic characteristics and clinical history, except that more patients had diabetes in the bifurcation subgroup (Table 1). 

There were some differences in angiographic characteristics (all visual estimates). The culprit lesion was more often located in the left anterior descending (LAD) coronary artery and patients had Thrombolysis in Myocardial Infarction (TIMI) grade 2/3 flow more often in the bifurcation subgroup (Table 2). 

Procedural characteristics were quite different between the subgroups (Table 2). Thrombus aspiration was performed less often, while predilation was performed more often, in the bifurcation subgroup. From the 123 patients treated for a bifurcation culprit, 81 (66%) were treated by placing the Stentys SAS over a >2.25 mm side branch (provisional single-stent strategy). In 65% of these 81 patients, the side branch was treated by side branch dilation/stent strut disconnection. 

There was a statistically significant difference in TVR rates between both groups (16.4% vs 10.0%; P=.04). There were no statistically significant differences for the other clinical endpoints, although MACE (12.7% vs 8.8%), clinically indicated TLR (10.3% vs 7.0%), MI (3.4% vs 1.8%), and definite/probable ST (5.8% vs 3.1%) rates were numerically higher in the bifurcation group (Table 3). 

When only considering those patients in whom the recommended postdilation was performed, we found similar rates between bifurcation and non-bifurcation lesions for most endpoints: MACE (8.7% vs 8.4%), TV-MI (1.2% vs 0.7%), clinically indicated TLR (5.1% vs 6.7%), and definite/probable ST (3.7% vs 2.4%), except for all-cause death (6.0% in bifurcations vs 2.2% in non-bifurcations; P=.04). 

Discussion 

These data suggest that primary PCI of a bifurcation culprit lesion using the Stentys SAS is feasible. If postdilation is performed, 1-year clinical outcomes were good and comparable to non-bifurcation lesions, especially when taken into account that the majority of bifurcations (66%) were treated with the BMS version of the device and that this analysis was performed in a STEMI population. 

Interestingly, the benefit of postdilation found in the APPOSITION III overall study population seems to be more pronounced in the bifurcation subgroup than in the non-bifurcation subgroup. In the non-bifurcation subgroup, clinical outcomes of the postdilation group appear to be very similar to the total group (ie, with and without postdilation). These findings suggest that postdilation is especially important in bifurcation lesions. 

One-year MACE rates in our bifurcation subgroup analysis (12.7%) were comparable to those found in the OPEN-II bifurcation study (13.0%), in which only stable patients were included and all were treated with the paclitaxel-eluting SAS.8 

Study limitations. The main limitation of the current study was that angiographies were not systematically collected; therefore, we could not verify whether the culprit lesion was indeed a bifurcation lesion or not. In addition, if the lesion was a bifurcation, we could not verify the exact treatment measures. As a result, we cannot determine why Stentys did not cross a side branch >2.25 mm in 42 patients of the bifurcation subgroup. It’s possible that the stent was positioned in one of the three bifurcation segments (ie, proximal main branch, distal main branch, or side branch), not crossing a side branch ostium, although this remains speculative. Randomized data are needed comparing contemporary DES with the newest (sirolimus-eluting) DES version of Stentys implanted with the new Xposition S delivery system for the treatment of bifurcation lesions.

Conclusion 

The use of the Stentys SAS was safe and feasible for the treatment of bifurcation lesions, even in the setting of primary PCI for STEMI, with acceptable cardiovascular event rates at 1 year. Clinical outcomes in bifurcation lesions improved considerably when postdilation was performed and became comparable with non-bifurcation culprit lesions. 

References

1.    Leesar MA, Hakeem A, Azarnoush K, et al. Coronary bifurcation lesions: present status and future perspectives. Int J Cardiol. 2015;187:48-57.

2.    Verheye S, Ramcharitar S, Grube E, et al. Six-month clinical and angiographic results of the Stentys(R) self-apposing stent in bifurcation lesions. EuroIntervention. 2011;7:580-587.

3.    Verheye S, Grube E, Ramcharitar S, et al. First-in-man (FIM) study of the Stentys bifurcation stent – 30 days results. EuroIntervention. 2009;4:566-571.

4.    Pyxaras SA, Schmitz T, Naber CK. The Stentys self-apposing(R) stent. EuroIntervention. 2015;11:V147-V148.

5.    Colombo A, Bramucci E, Sacca S, et al. Randomized study of the crush technique versus provisional side-branch stenting in true coronary bifurcations: the CACTUS (Coronary Bifurcations: Application of the Crushing Technique Using Sirolimus-Eluting Stents) study. Circulation. 2009;119:71-78.

6.    Steigen TK, Maeng M, Wiseth R, et al. Randomized study on simple versus complex stenting of coronary artery bifurcation lesions: the Nordic bifurcation study. Circulation. 2006;114:1955-1961.

7.    Hildick-Smith D, de Belder AJ, Cooter N, et al. Randomized trial of simple versus complex drug-eluting stenting for bifurcation lesions: the British bifurcation coronary study: old, new, and evolving strategies. Circulation. 2010;121:1235-1243.

8.    Naber CK, Pyxaras SA, Nef H, et al. Final results of a self-apposing paclitaxel-eluting stent for the percutaneous treatment of de novo lesions in native bifurcated coronary arteries study. EuroIntervention. 2016;12:356-358

9.    Amoroso G, van Geuns RJ, Spaulding C, et al. Assessment of the safety and performance of the Stentys self-expanding coronary stent in acute myocardial infarction: results from the APPOSITION I study. EuroIntervention. 2011;7:428-436.

10.    Koch KT, Grundeken MJ, Vos NS, et al. One-year clinical outcomes of the Stentys self-apposing(R) coronary stent in patients presenting with ST-segment elevation myocardial infarction: results from the APPOSITION III registry. EuroIntervention. 2015;11:264-271.

11.    van Geuns RJ, Tamburino C, Fajadet J, et al. Self-expanding versus balloon-expandable stents in acute myocardial infarction: results from the APPOSITION II study: self-expanding stents in ST-segment elevation myocardial infarction. JACC Cardiovasc Interv. 2012;5:1209-1219.

12.    Moretti C, Omede P, Presutti DG, et al. Shaping an ectatic coronary artery: Stentys implantation. Int J Cardiol. 2014;171:459-461.

13.    van Geuns RJ, Yetgin T, La Manna A, et al. Stentys self-apposing sirolimus-eluting stent in ST-segment elevation myocardial infarction: results from the randomised APPOSITION IV trial. EuroIntervention. 2016;11:e1267-e1274.

14.    Lu H, Grundeken MJ, Vos NS, et al. Clinical outcomes with the Stentys self-apposing coronary stent in patients presenting with ST-segment elevation myocardial infarction 2-year insights from the APPOSTION III (A Post-Market registry to assess the Stentys self-exPanding COronary Stent In AcuTe MyocardIal InfarctiON) registry. EuroIntervention. 2017 Feb 14 (Epub ahead of print).


From the 1Academic Medical Center – University of Amsterdam, Amsterdam, the Netherlands; 2Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands; 3Albert Schweitzer Ziekenhuis, Dordrecht, the Netherlands; 4Erasmus Medical Center, Rotterdam, the Netherlands; 5Cologne Cardiovascular and Chest Center, Cologne, Germany; 6Klinikum Bad Friedrichshall, SLK-Kliniken, Heilbronn GmbH, Germany; 7Ospedale Ferrarotto, Catania, Italy; 8Université Paris, ACTION Study Group, INSERM-UMRS, 9Institut de Cardiologie, Pitié-Salpêtrière University Hospital (AP-HP), Paris, France; and 10Stentys S.A., Paris, France.

Funding: The APPOSITION III study and associated data analysis were funded by Stentys S.A. (Paris, France).

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Drs Grundeken, Lu, Koch, Tijssen, Montalescot, Silvain, Amoroso, and Koch report research grants to their institutions from Stentys. Drs van Geuns and Wessely are members of the scientific advisory board of Stentys. Drs Amoroso, van Geuns, and Wessely report speaker fees from Stentys. Dr van IJsselmuiden reports consultant fees from Stentys. Dr Spaargaren is an employee of Stentys. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript submitted February 16, 2017 and final version accepted February 21, 2017.

Address for correspondence: Dr Karel Koch, Department of Cardiology, Academic Medical Center, Cardiac Catheterization Laboratory, Room B2-125, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. Email: k.t.koch@amc.uva.nl 

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