Single-center outcomes of Onyx Frontier™ and Resolute Onyx™ drug-eluting balloon-mounted stents for rescue stenting for acute large vessel occlusion

Abstract

Background

In cases where mechanical thrombectomy (MT) fails, rescue stenting may be necessary to achieve reperfusion; however, the lack of standardized techniques or devices poses a challenge. This series aims to present our early experience with the Onyx Frontier™ and Resolute Onyx™ balloon-mounted drug-eluting stents for rescue stenting.

Methods

A retrospective chart review was performed of all patients who underwent rescue stenting, in the setting of failed MT, using Onyx Frontier™ or Resolute Onyx™ stents at a single institution. Technical details, procedural complications, and patient outcomes were recorded for each case.

Results

Twenty-two Onyx Frontier™ and Resolute Onyx™ stents were deployed in 18 patients undergoing rescue stenting. Stent locations included the middle cerebral artery (36.4%), internal carotid artery (18.2%), vertebral artery (22.7%), and basilar artery (22.7%). The average National Institutes of Health Stroke Scale score before MT was 13.8 (range 0–31). The median initial modified Rankin Scale (mRS) score was zero, while the median mRS score at follow-up was three. Successful reperfusion, as assessed by TICI scores, was achieved in 43.8% of patients for TICI 3, 43.8% for TICI 2C, and 12.5% for TICI 2B. Post-revascularization, 16.7% of patients experienced hemorrhage, of which one patient (5.6%) had symptomatic hemorrhage.

Conclusions

Onyx Frontier™ and Resolute Onyx™ stents are well suited for rescue stenting in cases of failed MT. These balloon-mounted drug-eluting stents exhibit excellent navigability, rendering them appropriate for rescue revascularization procedures. Our findings demonstrate that these stents confer a high degree of technical success.

Introduction

The increasing global incidence and prevalence of ischemic stroke, driven by the aging population, have elevated stroke to the second leading cause of death and disability.^1,2 Mechanical thrombectomy (MT) has emerged as the standard of care for acute ischemic stroke resulting from large vessel occlusion in eligible patients.^3–8 However, MT has a failure rate of 20–30%,^5,9 generally attributed to significant vessel tortuosity, failure to obtain vascular access, and various underlying pathophysiologic conditions such as arterial dissection, iatrogenic endothelial injury, and in-situ thrombo-occlusion of intracranial atherosclerotic disease (ICAD).^10–13 Consequently, alternative interventions, including balloon angioplasty, intra-arterial thrombolysis, and rescue stenting have been considered in cases of failed MT.^14–16 Among these options, rescue stenting may be necessary to achieve reperfusion,^17,18 yet no standardized technique or device currently exists.

Systematic reviews investigating the efficacy of rescue stenting in cases of failed MT have consistently demonstrated favorable recanalization rates (approximately 80–90%) in both anterior and posterior circulation, and consequently superior functional outcomes compared to non-stenting treatments.^{11,13,19–24} These early reports have provided a strong impetus to utilize rescue stenting at our institution. This study aims to present the initial experience of a single institution regarding the utilization of Onyx Frontier™ and Resolute Onyx™ zotarolimus-eluting stents (Medtronic, Santa Rosa, CA) for rescue stenting following failed MT. These stents are FDA approved for coronary use; therefore, their use for rescue stenting is off-label. The Onyx Frontier™ stent is newer than the Resolute Onyx™ stent, and while both stents use the same stent platform, the Onyx Frontier™ has a few improvements. These include catheter flexibility without compromising on radial strength, a dual-layer balloon, and a lower crossing profile. The existing literature lacks specific reports on the use of Onyx stents in patients undergoing MT. To address this gap, we discuss initial outcomes and feasibility of employing these stents in the context of rescue stenting procedures.

Methods

A comprehensive retrospective chart review was performed of all patients who underwent rescue stenting, in the setting of failed MT for occlusive lesions and residual ICAD after clot removal, using Onyx Frontier™ or Resolute Onyx™ stents, at a single institution. Stenting was not done for dissections or sub-occlusive thrombi. Technical details, procedural complications, and patient outcomes were recorded for each case. The study protocol received institutional review board approval. The need for patient consent was waived given the retrospective nature of the review. A total of 18 patients underwent rescue stenting with Onyx Frontier™ or Resolute Onyx™ stents. Patient-specific data, including age, sex, vessel occluded, National Institutes of Health Stroke Scale (NIHSS) before treatment, initial modified Rankin Scale (mRS) score, mRS at follow-up (median 12 months), and post-procedure neurological complications, were collected. Procedural and radiological data included the number of stents deployed, stent length and diameter, stent location, technical and procedural complications, use of intra-arterial tissue plasminogen activator (tPA), medications used after procedure, proximal vessel diameter, number of passes prior to rescue stenting, type of attempted MT, and CT perfusion core and penumbra volumes.

Statistical analyses, including summations, means, median, mode, ratios, and ranges, were performed using Microsoft Excel (Microsoft Corporation, Redmond, WA).

Stenting technique

The most common guide sheath used was the BMX 96 (Penumbra, Alameda, CA). When rescue stenting was performed, the intermediate or aspiration catheter was exchanged for a 5F SOFIA EX (Microvention, Aliso Viejo, CA) intermediate catheter; although, in select cases, the aspiration catheter remained unchanged. Prior to stent deployment, a 20-s DYNA cone-beam CT was performed to evaluate the presence of intracranial hemorrhage (ICH). To facilitate navigation of the stent, the intermediate catheter was advanced beyond the origin of the ophthalmic artery, as negotiating this curve without the support of an intermediate catheter can be challenging. The stent diameter was usually selected to be approximately 0.25 mm smaller than the proximal vessel diameter to minimize the risk of oversizing. Stenting was accomplished by initially passing the stenotic lesion with a microcatheter and subsequently introducing an exchange-length Synchro support microwire (Stryker, Fremont, CA) to remove the microcatheter and load the stent system. Either an intravenous infusion of cangrelor at 2 mcg/kg/min or an intra-arterial bolus of 10 mg of eptifibatide was administered as the initial antiplatelet therapy 5 to 10 minutes prior to stent deployment. Rapid exchange stents were used in all cases. The balloon-mounted stent was navigated to the lesion and inflated to the appropriate diameter at six to ten atm (sub-nominal). The system was then removed after visual confirmation that the stent had been completely deployed. Following the procedure, a micro DYNA CTA was performed to ensure adequate stent expansion and vessel patency. Post-procedure, rectal aspirin (300 mg) was administered in the angiography suite (Figure 1).

Figure 1.

Sample case: Left proximal MCA occlusion (proximal vessel diameter of 2.3 mm) seen on anterior–posterior (a, b) and lateral (c) runs. A 2 × 12 mm Onyx Frontier™ stent was deployed across the area of occlusion (d). Subsequent runs following stent deployment demonstrated recanalization of left MCA (e–g). (h) Three-dimensional reconstruction of stent construct within left MCA. Of note, this patient had a prior left MCA aneurysm that was embolized with pipeline devices. MCA: middle cerebral artery.

Results

Over the study period, 18 patients were treated with 22 Onyx Frontier™ or Resolute Onyx™ stents for rescue stenting in the setting of failed MT (Table 1). Five patients were female (27.8%). The average age was 62.8 years (range 31 to 88 years). 13/18 (72.2%) of cases used Resolute Onyx™ stents whereas 5/18 (27.8%) of cases used Onyx Frontier™ stents.

Table 1.

Results and procedural characteristics of 18 patients who underwent rescue stenting with Onyx stents following failed mechanical thrombectomy.

Onyx stent type	Stent location	Number of stents	Stent size (s) (mm)	TICI	Use of tPA	Post-procedure hemorrhage
Resolute	MCA	2	8 × 2; 8 × 2.5	2C	No	No
Resolute	VA	1	12 × 3.5	2C	Yes	No
Resolute	ICA	1	12 × 2.25	3	Yes	No
Resolute	VA	1	15 × 2.5	NR	No	No
Frontier	MCA	1	8 × 2	2C	Yes	No
Frontier	ICA	1	15 × 3	3	No	No
Resolute	VA; BA	2	12 × 3; 15 × 3	3	Yes	No
Resolute	ICA; MCA	2	12 × 2.5; 8 × 2.75	2B	No	No
Resolute	ICA	1	12 × 4	3	Yes	No
Resolute	BA	1	12 × 2.5	3	No	No
Resolute	MCA	1	8 × 2	2C	No	Basal ganglia IPH
Resolute	BA	1	22 × 3	2B	No	Temporo-occipital ICH
Resolute	BA	1	12 × 2.5	3	No	No
Frontier	BA	1	8 × 2.75	2C	No	No
Resolute	MCA	1	12 × 3.5	N/A	No	Pancisternal SAH
Frontier	MCA	1	12 × 2	2C	No	No
Frontier	VA	2	15 × 3; 12 × 3	2C	Yes	No
Resolute	MCA	1	8 × 2	3	No	No

tPA: tissue plasminogen activator; MCA: middle cerebral artery; VA: vertebral artery; BA: basilar artery; ICA: internal carotid artery; ICH: intracranial hemorrhage; SAH: subarachnoid hemorrhage; N/A: not applicable; NR: not recorded.

The average core stroke volume was 6.6 cc while the average penumbra volume was 137.9 cc on CT perfusion. Prior to attempting MT, 33.3% of patients received tPA. The median number of passes prior to attempting rescue stenting was two (range 1–6). Stentriever and aspiration were attempted in the majority (77.8%) of patients, stentriever alone was attempted in one patient (5.6%), and aspiration alone was attempted in 16.7% of patients. Stent locations were distributed as follows: 36.4% in the middle cerebral artery (MCA), 18.2% in the internal carotid artery (ICA), 22.7% in the vertebral artery (VA), and 22.7% in the basilar artery (BA). The median number of stents deployed was one. The average NIHSS score before MT was 13.8 (range 0–31). The median initial mRS score was zero (range 0–2), while the median mRS score at follow-up was three (range 0–4). TICI 3 was achieved in 43.8% of patients, TICI 2C in 43.8% of patients, and TICI 2B in 12.5% of patients. The average proximal vessel diameter was 2.9 mm (1.8–4.2 mm), and the most used stent length was 12 mm, with stent diameters of 2 mm or 3 mm being the most frequently chosen.

Among all patients, only one (5.6%) had symptomatic hemorrhage (i.e. pancisternal SAH)—based on the Heidelberg bleeding classification—due to vessel rupture, which required hemicraniectomy. This was the only technical/procedural complication observed, which occurred due to stent oversizing. Among the two patients (11.1%) with asymptomatic hemorrhage (both small IPH), all received aspirin (81 mg or 325 mg) followed by a cangrelor drip, which was later transitioned to clopidogrel or ticagrelor.

No pre- or post-stenting angioplasty was necessary for any device, and there were no difficulties in positioning or delivering the device. Of the 18 patients, only six (33.3%) received moderate-to-long interval follow-up imaging (CTA, MRA, and/or angiography), which was done at 1–9 months following stent placement. Of those six patients who received imaging, five had patent stents (83.3%) and only one showed stenosis (moderate). One patient received a short-interval MRA 2 weeks after stent placement showing occlusion, which is the only occlusion case in this series.

Discussion

Acute ischemic stroke is one of the leading causes of worldwide morbidity and mortality, and MT has emerged as the standard of care for appropriately selected patients.^1,6 Although MT is successful in over 70% of cases, a subset of patients requires adjunctive treatments, including rescue stenting, to achieve adequate reperfusion.^5,17 Extensive research has demonstrated that rescue stenting is linked to favorable long-term functional outcomes and has an acceptable safety profile.^22,23 Nevertheless, the specific type of stent employed in rescue stenting remains an understudied variable in the existing literature.

The current literature pertaining to stent utilization in rescue stenting is highly heterogenous, with different groups reporting use of various devices, such as the original Solitaire™, ENTERPRISE™, and Wingspan®, none of which are necessarily deployed according to their on-label indications. ²⁵ Many authors have described that stent selection was performed at the discretion of the treating interventionalist, with no explicit mention of the specific device employed. A limited number of reports exist detailing the use of non-neurovascular stenting systems for rescue stenting following failed MT. Case reports have documented the implementation of coronary stents in rescue stenting following stent thrombosis ²⁶ and vessel dissection. ²⁷ Additionally, a case series has described the use of coronary stents to expand access to rescue stenting in low- and middle-income countries ²⁸ with favorable technical performance and revascularization outcomes. It is worth mentioning that two patients in this series underwent rescue stenting using the Resolute Onyx™ stent, with neither experiencing symptomatic ICH.

Periprocedural considerations hold significance in the overall management of rescue stenting. For instance, a multicenter prospective registry found that follow-up patency of the rescue stent was a crucial factor for favorable outcomes. ²⁴ Notably, the use of glycoprotein IIb/IIIa inhibitors, such as eptifibatide, following rescue stenting was significantly associated with improved outcomes. ²⁴ Furthermore, a systematic review and meta-analysis indicated that the administration of antiplatelet agents following rescue stenting does not heighten the risk of ICH. ¹¹

The Onyx Frontier™ and Resolute Onyx™ stents are zotarolimus-eluting stents that have exhibited both safety and efficacy in percutaneous coronary intervention.^29,30 Multiple high-impact studies, including those by Hassan et al. and Mohammaden et al., have also demonstrated the technical success, safety, and short-term effectiveness of the Resolute Onyx™ stent for symptomatic ICAD and acute ischemic stroke.^31–34 While this is different in application compared to rescue stenting for failed MT, the principles of safety and feasibility remain closely related.

In this study, patients who were deemed suitable for MT displayed favorable pre-infarction functional status but presented with significant neurologic deficits; 33.3% of patients received thrombolysis prior to MT, comparable to the rates reported in the general rescue stenting literature. ²⁴ Stent placement was distributed relatively evenly between the anterior and posterior circulations, with 54.5% deployed in the MCA or ICA, and 45.5% in the VA or BA. Excellent reperfusion (TICI 3 or 2C) was achieved in 90% of all patients treated with Onyx stenting, while the remaining patients achieved TICI 2B reperfusion. These findings are consistent with the upper end of reported recanalization rates (ranging from 65% to 96%) in the general rescue stenting literature.^14,21

The median number of passes prior to rescue stenting was two, which seems low. Among the six cases where the number of passes was one, all of them had underlying ICAD stenosis and evidence that further passes would not prevent artery in question from shutting down again. Based on interventionalist discretion, it was thought that more passes would increase the risk of vessel injury and, in these selected cases, more passes were thought to be of minimal or no benefit. Therefore, the decision was made to rescue stent after just one pass.

ICH occurred in 3/18 (16.7%) of patients, but only one patient (5.6%) experienced symptomatic ICH (i.e. pancisternal SAH) attributed to a technical complication. Among the asymptomatic hemorrhages, one was a right basal ganglia ICH in a case where the right M1 was stented, and the other was a right temporo-occipital ICH in a case where the BA was stented. Therefore, both hemorrhages could be attributed to reperfusion and/or distal hemorrhagic transformation from thrombolysis and antiplatelets. With the relatively small sample size in this cohort, the symptomatic ICH rate of 5.6% is within the reported range of 4–11% observed in previous rescue stenting trials.^25,35

No post-stenting deaths were reported, reflecting an improvement compared to the reported mortality rate ranging from 10% to 23% in the literature.^14,25,36 Functional outcomes in this cohort were acceptable, with a median mRS of 3. This may have been influenced by the limited sample size in this cohort, as other studies have reported approximately 50% of patients have an mRS of 2 or less following rescue stenting.^14,36 These preliminary findings suggest that rescue stenting using the Onyx Frontier™ and Resolute Onyx™ stents represents a highly effective technique for achieving reperfusion following unsuccessful MT in acute ischemic stroke. Safety parameters and outcomes appear to fall within the reported range in prior trials of other devices. Further investigations involving larger patient populations are necessary to provide more robust assessments of safety and long-term outcomes associated with rescue stenting using Onyx stents. In addition, larger sample sizes would enable important subgroup analyses to be conducted.

There are several limitations to this study including small sample size and retrospective nature; however, the former is understandable since Onyx stents are FDA approved for coronary use and have only recently been used off-label in cerebral angiography. Small studies like this one are important to demonstrate the versatility of devices, such as the Onyx stents, to develop a basis for further study. Another limitation to the study is the lack of follow-up imaging to determine stent patency. Only six patients received any form of moderate-to-long interval follow-up imaging. Of those that did, however, over 80% demonstrated stent patency.

Onyx Frontier™ and Resolute Onyx™ stents are additional tools in interventionalists’ armamentariums in the event of failed MT. Despite studies demonstrating the safety and efficacy of rescue stenting, ultimately, the safety and efficacy of these stents will be determined by the interventionalist's knowledge, technical expertise, and experience. The introduction of these stents for rescue stenting could potentially improve revascularization rates in the setting of failed MT for acute large vessel occlusion.

Conclusion

In cases of failed MT, Onyx Frontier™ and Resolute Onyx™ stents exhibit a high level of technical success and, hence, can serve as effective options for rescue stenting.