Stroke is one of the leading causes of long-term disability and 2nd most common cause of mortality in the world. Every year almost 800,000 Americans approximately suffered from stroke [1,2]. About 600,000 of those suffer from a first or new stroke. Age is one of the most common risk factors for stroke. For each successive 10 years after age 55, the stroke rate more than doubled in both men and women [3]. Nearly three quarters of all strokes occur in older than 65 years. Timely intervention is crucial as only approved treatment for acute ischemic stroke (AIS) alteplase (tPA) and mechanical thrombectomy (MT) are both times sensitive. Older adults may also be at increased risk of hemorrhagic complications from these treatments [4,5]. Patient older than 80 years were often excluded from clinical trials for both types of treatment [6,7]. People older than 80 years of age represent the fastest growing population in the US as well as other developed countries [8]. While intravenous tissue plasminogen activator (IV tPA) and endovascular thrombectomy (EVT) with advanced imaging showing salvageable tissue become Class-I level of evidence A recommendation for the standard management in patients with acute ischemic AIS, the debate continues about the use IV tPA and/or EVT in the frail elderly with AIS given concerns for age-related brain pathology and systemic functional fragility. Reported randomized trials with IV tPA and EVT did not independently study the efficacy of IV tPA and/or EVT in this particular population. A HERMES sub study [9] demonstrated that patients age greater than 85 years old with independent premorbid function more often achieve favorable functional outcomes and have lower rates of mortality when treated with EVT compared to conservative medical management. The outcome after EVT in elderly patient age above 80 years with AIS remains inconclusive and mixed, particularly the bridging therapy with thrombolytic agent and EVT in this patient population.

Timely administration of IV tPA is the standard treatment for eligible patients within the therapeutic time frame of 3-4.5 hours [10]. Within the 6 hours of symptom onset, additional EVT with a stent retriever can be performed in patients with LVO [11]. Recent prospective clinical trial results supported the use of MT within a 24-h time window for patients with evidence of significant penumbra, demonstrated with advanced imaging of computed tomography (CT) or magnetic resonance imaging (MR) perfusion scan [12,13]. But in patients over 80 years old accounted for about one-third of all stroke admissions, the risk and benefit of IV-tPA and EVT in this growing population remain unclear and inconclusive. Old patients (age>80 years) were often excluded from large clinical trials, due to a predetermined upper age limit. Some recent studies have shown that EVT carried a significantly high risk of mortality and morbidity in elderly stroke patients aged over 80 years despite a successful recanalization, whereas others found that octogenarian patients with AIS appeared to be beneficial more from EVT compared to received tPA alone [14]. Regardless similar improvements in post-EVT NIHSS of older and younger patients, high mortality rates and less frequent favorable functional outcome have been noted in elderly patients despite successful recanalization of the LVO [15]. Recently published SKIP study failed to demonstrate a non-inferiority of mechanical thrombectomy alone versus combined intravenous thrombolysis and mechanical thrombectomy treatment [16]. On the other hand, SWIFT and STAR trials did not show any added benefit of intravenous thrombolysis before mechanical thrombectomy in patients with AIS in the setting of LVO [17].

We identified patients from our daily practice who were consecutively admitted with the diagnosis of AIS to Spectrum Health Butterworth Hospital (a large tertiary comprehensive stroke center), from January 1, 2017 to December 31, 2019. The study proposal was approved by our institutional review board (IRB). Nighty eight AIS patients (age >80 years old) with LVO who received EVT with or without IV tPA was included in the study. Inclusion criteria included all elderly acute stroke patients (>80 years of age) with LVO received EVT with or without IV tPA as bridging therapy. Exclusion criteria included AIS patients ≤80 years of age. Patient data was reviewed using the electronic medical record that is used at Spectrum Health Butterworth. Data collection will included: age, sex, race, date of admission, vascular study: results of imaging available in the electronic medical record pertaining to stroke (head CT, CT angiogram, brain MRI, and repeated head CT at 24-hour post EVT), lab results pertaining to ischemic stroke including low density lipoprotein( LDL) and hemoglobin A1c, neurological exam results including NIHSS (initial score upon ED arrival, 24- hour post EVT, at hospital discharge, and at 3-month post EVT if available). Modified Rankin score (mRs) at baseline, at hospital discharge, and at 90-day follow up, if available, whether patient received IV tPA and use of prior anti-thrombotic.

Quantitative, normally distributed data are expressed as the mean+SD, while non-normally distributed quantitative data are expressed as the median (minimum, maximum). Nominal data are expressed as a percentage. Comparisons between groups for normally distributed quantitative variables were performed using the two tailed, unpaired t-test, while non-normally distributed quantitative data were analyzed using the Mann Whitney test. Nominal variables were evaluated using the chisquare test or the Fisher’s Exact test, as appropriate. Comparisons of NIHSS scores (initial verse discharge, mild/moderate verse severe) were performed using the McNemar test. Significance was assessed at p<0.05. All analyses were performed using Stata v.16.1 (StataCorp, College Station, TX).

We included total of 98 patients in the study. We subdivided these patients who underwent EVT into two groups on the basis of patients who received intravenous thrombolysis versus who did not. We had total of 34 patients who received bridging therapy of both EVT and intravenous thrombolysis and 64 patients in the other group who only underwent EVT. We did not see any statistical difference (Table 1) between the 2 groups in terms of their age and sex (p=0.957 and 0.08, respectively). We also did not see any statistically significant difference in their medical comorbidities (Table 1). When we look at the primary functional outcome on the basis of mRS, overall functional outcome when compared to DAWN trial controls as showing in Figure 1 there was no statistically significant difference between the 2 groups at 90 days mRS.

When we look at the secondary outcomes between the 2 groups, we did not find significant statistical difference in terms of functional recovery at 90-day post stroke in elderly population (octogenarian and nonagenarians) between the endovascular treatment alone versus dual therapy of intravenous thrombolysis and endovascular treatment (Figure 1). We also did not find significant statistical difference in terms of mortality and hemorrhagic complications (p= 0.818 and 0.823, respectively) (Table 1). Our results are consistent with some of the recent studies that showed EVT alone is non-inferior to dual therapy of intravenous thrombolysis and EVT.

We also compared patients who presented initially with mild to moderate NIHSS versus severe initial NIHSS between the 2 groups and improvement in NIHSS at discharge. As showed in (Figure 2A, 2B) patients who came in with severe initial NIHSS had significant improvement in NIHSS at discharge as compared to those patients with mild to moderate initial NIHSS. These findings are consistent in both subgroups of patients who received IV thrombolysis plus EVT versus EVT alone.

We studied benefits of endovascular therapy in elderly population (octogenarian and nonagenarians) with acute ischemic stroke due to large vessel occlusion (LVO). We also compare benefits of bridging patients with intravenous thrombolysis before endovascular treatment versus endovascular treatment alone. In addition, we looked into adverse effects mainly hemorrhagic complications between the two groups. Our study showed that EVT alone in elderly population is noninferior to dual therapy with intravenous thrombolysis plus EVT. No overall benefit was observed on primary functional outcome of mRS at 90 days, when compared to the control group from DAWN trial patients with age greater than 80. Complex multiple comorbidities in this elderly age group could impact on their overall outcome, at least in part. Some people deceased in the setting of their other comorbidities or due to a decision made for hospice. The major trials have very strict inclusion criteria of baseline mRS of 1-2 which is sometimes not possible in the realworld practice. Recent clinical trials, SWIFT and STAR showed similar findings of dual therapy of intravenous thrombolysis plus EVT did not provide any added benefit in acute stroke patients with LVO. However, the HERMES collaboration [9] demonstrated the positive effect of EVT on outcome was maintained in the subgroup of patients age ? 85 years; those who underwent EVT had better functional outcomes and lower mortality rate compared to those who received standard medical managing at 90 days after AIS. The functional benefit of receiving EVT along or bridging therapy with IV thrombolysis and EVT in elderly stroke patients remains mixed to date.

Surprisedly, the difference of mortality and hemorrhagic complications was not found between two groups (bridging therapy of tPA and EVT compared to EVT alone) in the present study. Additionally, our study did not find any statistically significant correlation between previous antithrombotic use (antiplatelet or anticoagulation) and hemorrhagic complications in patients underwent EVT. In sub-analysis, we compared patients who presented initially with mild to moderate NIHSS versus severe initial NIHSS between the 2 groups and improvement in NIHSS at discharge. As showed in (Figure 2A,2B) patients who came in with severe initial NIHSS had significant improvement on NIHSS at discharge as compared to those patients with mild to moderate initial NIHSS. These findings are consistent in both subgroups of patients who received IV thrombolysis plus EVT versus EVT alone. Unfortunately, this transient functional improvement did not sustained reflecting by no observed benefit at 90-day after AIS. Underlying mechanisms of this noted non-sustained benefit in elderly AIS patients with serve NIHSS are obscure. Complex medical comorbidities and system non-neurological complications might play a major role in this observed phenomenon.

This study has several limitations, primarily being a retrospective study with data collection from a single tertiary center. Significant ethnic bias might impact on the study result in the setting of Caucasian is the dominant race in our study population. In addition, a small sample size in this study may make it difficult to extrapolate the results to the overall population.

In conclusion, this study showed that in elderly population (octogenarian and nonagenarians), endovascular treatment alone is non-inferior to dual therapy of intravenous thrombolysis plus endovascular treatment in the setting of LVO in patients with acute ischemic stroke. Overall primary functional outcome mRS at 90 days are not very promising in this age group but there are other different factors that could impact on it. This study also demonstrated that appropriate patient selection should be considered and bridging therapy or EVT alone should not be withheld in this elderly group. Direct thrombectomy in very elderly stroke patients with LVO appears reasonable to avoid potential hemorrhagic transformation from bridging therapy. Large multicenter trials in this population are needed to compare thrombolytic plus DVT with endovascular therapy alone.

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