Clinical Outcomes of Endovascular Thrombectomy in Tissue Plasminogen Activator versus Non-Tissue Plasminogen Activator Patients at Primary Stroke Care Centers

INTRODUCTION

Improved clinical outcomes for patients with acute emergent large vessel thromboembolic cerebrovascular accidents (CVA) at high-volume centers have been demonstrated. Prolonged transfer times to such institution are associated with less favorable outcomes. Direct access to smaller thrombectomy-capable low-volume centers is in most cases the only immediate viable revascularization option. The development of primary stroke centers and intravenous tissue plasminogen activator (IV tPA) administration protocols have established clear metrics for treatment with improved clinical outcomes’ event at these smaller centers.[1] The efficacy of endovascular reperfusion in emergent large vessel occlusion has been verified by five landmark studies. Rapid complete revascularization with minimizing risk is a prerequisite for favorable clinical outcomes.[23] IV tPA administration before endovascular intervention at thrombectomy-capable low-volume centers and how this affects procedural aspects and patient outcomes have not been investigated. This study was performed to determine if patients who qualify for endovascular intervention benefit from prior IV tPA administration at low-volume thrombectomy-proficient centers.

METHODS

This was an Institutional Review Board-approved study with waived individual consent. Retrospective chart review of all consecutive CVA patients treated with endovascular therapy at two select rural primary stroke centers between 2011 and 2015 was performed. Inclusion criteria were all anterior circulation large vessel occlusions within an 8 h time window from symptom onset with subsequent endovascular intervention.[4] Patients’ data regarding age, sex, and medical history, as well as thrombus location by catheter-based cerebral angiography and postprocedural reperfusion status were reviewed. Computed tomography (CT) head to procedure commencement time was determined from the time of CT acquisition recorded to the time documented in the chart as the time of procedure commencement. Total procedural times were obtained from the chart as noted by the time the procedure commenced to the time the procedure was considered complete, inclusive of anesthesia time and groin arteriotomy closure device placement. Revascularization was performed with a mechanical stent retriever, aspiration or a combination of local aspiration, and mechanical thrombectomy. Successful recanalization was defined as modified thrombolysis in cerebral infarction (TICI) score of 2b or 3. The initial NIHSS and the 90-day functional outcome were assessed using the modified Rankin scale (MRS) at a follow-up neurology visit. The primary outcome measure of the study was a comparison of MRS at 90 days in patients with IV tPA administration before thrombectomy versus those who did not qualify for IV tPA administration. A Modified Rankin Score of ≤2 at 90 days was considered a good functional outcome. All data points above were stratified into IV tPA versus no-IV tPA for comparison.

RESULTS

DISCUSSION

Patients undergoing endovascular thrombectomy for large vessel occlusion at select low-volume rural centers in our study showed benefit from this treatment regardless of IV tPA administration. The benefit of prethrombectomy IV tPA in improving clinical outcomes has been controversial.[56] A prospective study identified a dramatic improved functional outcome of 51.5% with prethrombectomy IV tPA administration versus 18.2% for endovascular intervention alone.[7] A meta-analysis of five studies comparable to our study period identified 37.2% good functional outcomes with thrombectomy alone and 49.2% with combined therapy.[8] Functional outcome in the thrombectomy alone group in our study was 43.4% and 39.1% with combined therapy, which was not statistically significant. In comparison to studies at a similar time period,[239] reperfusion rates and clinical outcomes of our data are comparable to most comprehensive stroke centers with large volumes as well as the landmark studies proving the efficacy of endovascular treatment.

IV tPA theoretically facilitates thrombus dissolution and may address more distal or procedural new territory small vessel thromboembolism. This may translate to increased recanalization rates and decreased procedural times. In our study, the overall time from CT scan to procedure start in each group was not statistically significant. Administration of IV tPA requires clinical decision-making and drug preparation that delays noncontrast head CT to procedure commencement time. In our study, an average delay of 15.6 min was identified with IV tPA administration that was not statistically significant. At low-volume centers, prolonged symptom onset time to endovascular reperfusion has been identified, without published data identifying the root causes.[10] Potential reasons for workflow inefficiency include delays in considering endovascular therapy, staffing with nondedicated endovascular neurointerventional call teams, the use and availability of general anesthesia, operator experience, and lack of dedicated neurocritical care. Given that the workflow times may be longer at low-volume centers, the addition of IV tPA bridging to mitigate this potential delay did not appear to be advantageous in our study. Our data identified increased symptomatic and nonsymptomatic intracranial hemorrhages in the combined therapy group, which was not statistically significant. The only intracranial hemorrhage-related mortality postthrombectomy was in the thrombectomy with IV tPA group. This is comparable to data from a published study of 1275 patients.[8]

Comprehensive high-volume center data have shown a superiority in measured efficiency for times to recanalization and outcomes when compared to low-volume centers.[10] Access to comprehensive centers may not always be a feasible option. Seventy percent of high-volume centers are more likely to be urban teaching hospitals.[11] For multiple centers’ concentrated large urban environments, it is a plausible premise to direct patient care to the highest volume center. In nonurban rural areas, often further than an hour travel time from a comprehensive center, a thrombectomy-capable primary care center is a more viable alternative. Theoretically, only 56% of the US population have access to endovascular-capable hospital by road in 1 h.[12] For every 1 h delay in reperfusion, the odds of good clinical outcome decreases by 38%.[13] A prolonged symptom onset to reperfusion time has been shown to be an independent limiting factor for favorable outcomes.[14] Transfer delay is a major factor limiting the use of intra-arterial treatment in acute ischemic stroke and significantly limits favorable outcomes.[915] One in four patients becomes ineligible for endovascular thrombectomy during transfer with a trend toward poorer outcomes once transferred.[16] The mortality rate is significantly lower in directly admitted patients as compared to transferred patients.[17] Primary care centers capable of thrombectomy, with established and sustained treatment time proficiency protocols, will reduce the number of patients requiring transfer and reduce symptom onset to reperfusion times with resultant improved functional outcomes.

A larger proportion of ischemic stroke patients will be treated at low-volume centers. The incidence of large vessel occlusion has been determined to be 24 per 100,000 person-years and, the most recently estimated annual thrombectomy rate in 2015 of three procedures per 100,000 people indicates that there will be a significant increase in the volume of endovascular procedures.[18] The mean number of thrombectomy cases per institution was 19.3 cases per year in an outcome report database. Nearly 89% of institutions reporting to this database were university hospitals.[17] This falls well short of the 38 thrombectomy cases recommended for thrombectomy-capable centers and far short of the 50 cases suggested as a designate high-volume center.[1019] Almost a decade ago, only 0.4%–2.6% of hospitals met the procedural volume recommended by various professional bodies for endovascular thrombectomy.[11] In spite of less favorable outcomes with carotid stenting, a lower proportion of cases are currently treated at high-volume centers.[20] In the state of New Jersey as an example, 60% of stroke admissions were at a primary stroke center as compared to 40% at a comprehensive center.[21] As with carotid stenting, an increase in procedures for large vessel occlusions in thrombectomy-capable low-volume centers is probable with the anticipated increase in procedural volume.

The study is limited by the nonrandomized retrospective nature and the small number of patients in each cohort. The results of select rural centers that have clinical neuroscience services may not reflect outcomes at all rural-based hospitals. The findings of this study may be reflective of other rural institutions that have available resources including appropriate equipment as well as skilled technical and physician staff that will and can promote aspects of care for better functional outcomes. These centers should rather be considered as thrombectomy-proficient centers.

CONCLUSION

Optimizing care at thrombectomy-proficient low-volume institutions with high-volume center partnership and collaboration is a more tangible goal than promoting transfers out of primary stroke centers as the only viable option for favorable outcomes. Empowering these rural-based thrombectomy-proficient centers with preparedness tools, fostering a vigilant mindset, and frequent staff and physician training to focus on efforts directed at achieving faster recanalization times may allow for continued improvement in patient outcomes that will remain consistent with national data.[22] Further studies are needed to identify the patient population that would benefit from endovascular intervention without tPA administration when compared to the currently favored model of combined therapy.