Discussion

Acute ischemic stroke is the third leading cause of death in the USA and the most prevalent neurologic diagnosis. It is also the most common diagnosis in nursing home residents. With advancements in medicine and prolongation of life expectancy, stroke commonly affects the elderly. Unfortunately, there are minimal data to support acute endovascular intervention in this patient population. Additional studies are currently underway with the recent publication of the Thrombolysis in Elderly Stroke Patients in Italy (TESPI), a randomized, controlled trial evaluating intravenous tissue plasminogen activator versus standardized medical therapy in patients >80 years of age, which is currently underway.28

Existing medical comorbidities such as diabetes, hypertension, cardiac history and renal insufficiency increase perioperative patient risk. Furthermore, vascular anatomical limitations, such as diffuse atherosclerosis, vessel tortuosity and peripheral vascular disease, pose additional surgical risks in the elderly. Yet, rapid reperfusion of the cerebral penumbra remains the gold standard in acute stroke care. The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) supported the notion that ICA stenting is comparable with carotid endarterecomy in terms of perioperative morbidity and mortality after 30 day and 2.5 year follow-ups.28 Later analysis of the CREST data suggested a correlation between increasing age and risk of stroke.28 ,29

In our series, we investigated the safety and efficacy of multimodality endovascular intervention for acute ischemic stroke in septuagenarians and above. Due to the high surgical risk in this patient population, careful inclusion criteria were set. The angiographic revascularization rates were good, with a mean TIMI score of 2 post-recanalization, with 34 patients (67%) achieving TIMI scores of 2 or greater. Perioperative morbidity was 27.5%, due to 13 intracranial and one retroperitoneal hemorrhage. Only three (5.8%) of the 13 intracranial hemorrhages were symptomatic. This was less than half the reported rate of symptomatic intracranial hemorrhage in an analysis of the PROACT II (Prolyse in Acute Cerebral Thromboembolism II) study.30 In the aforementioned study, blood glucose >200 mg/dl was associated with a 36% increased risk of intracranial hemorrhage. The prevalence of diabetes type I or II was higher in our population (23.5%), but in our case, this did not increase the rate of hemorrhage. The addition of angioplasty and or stent placement did not appear to have an impact on the overall incidence of intracranial hemorrhage, despite the need for clopidogrel post-intervention. Thirty-four per cent of patients underwent stent placement. While off-label, stent placement has increasingly been performed in acute stroke, to maximize flow restoration, with favorable results.10–12 31–33 In the non-operative population, hemorrhagic conversion has been reported to range from 15% to as high as 43%.34 Our procedural death rate was 3.9%, which was due to vessel rupture, as evidenced by contrast extravasation intraoperatively. In previous series of elderly patients, time from ictus to endovascular intervention ranged from a mean of 4.3 to 6.25 h.21 ,35 Our study had an average time to intervention of 6.1 h. As a tertiary referral center, most patients at our center are evaluated at an outside institution and then transferred on clinical suspicion of stroke. The use of CTP criteria (which allowed the extension of the therapeutic window) to select patients for endovascular intervention also explains the long interval from stroke onset in our study.

Recently, Galimanis et al prospectively followed 623 patients who underwent endovascular recanalization for stroke. They concluded that ‘time to treat’ was the only significant factor leading to a better outcome.36 Of one of the largest series to date involving multimodal recanalization, they found a 5.5% incidence of symptomatic intracranial hemorrhage. Qureshi et al9 in his study of patients over 80 years old found a rate of 12% intracranial hemorrhage. We found 13 hemorrhages (25.4%) on postoperative routine imaging. Almost half of these patients had stent placement. A similarly high rate of hemorrhage was also reported by Loh et al8 (61%). Difficulty arises in comparing rates of hemorrhage after intervention for a number of reasons. In our series, the added risk of hemorrhage from stent placement is unknown. Most importantly, 45% of our elderly cohort received intravenous tissue plasminogen activator prior to treatment, compared with 13% in the series by Qureshi and 35% by Loh et al8 (intra-arterial and intravenous combined). Use of intra-arterial lytics to date has not used a standardized dose, which also does not allow for an even comparison across these three studies. Lastly, Loh et al utilized thrombectomy in all of their patients, without the use of stent. The observed morbidity and mortality in our study (21%) compares favorably with those of Qureshi et al (54%) and Loh et al8 (48%).

The goal of stent placement in the setting of acute ischemic stroke is recanalization of the occluded vessel. Recanalization has been shown by Rha et al37 to have a favorable clinical impact on meta-analysis. A retrospective review of 115 patients by Al-Ali et al showed that angioplasty had a lower 1 year risk of recurrent or new stroke than medical management with warfarin and aspirin. In their study, the risk of stroke was very similar when comparing bare metal stent to medical management (19% vs 18%, respectively).38 Stenting for flow restoration in stroke is feasible with high rates of recanalization.5 Stampfl et al showed successful recanalization with stenting in 89% in acute stroke.5 Brekenfield et al followed prospectively 40 consecutive patients with acute ischemic stroke; 43% of patients underwent Wingspan (Boston Scientific) stenting and 57% of patients underwent thrombectomy alone with the Solitaire FR revascularization device (ev3, Plymouth, Minnesota, USA). Median ages were comparable (66 and 68 years in the two groups, respectively). The stented group showed superior rates of recanalization, and earlier time to flow restoration is seen, which were statistically significant.39 Compared with thrombolysis alone, stent placement demonstrated higher rates of recanalization as well as comparable morbidity.40

The median age in this group was 81 years. One would expect a higher morbidity when the results of stroke studies are translated clinically. Stenting requires a minimum vessel compliance to achieve vessel recanalization safely. In human studies, Van Lammeren et al41 harvested 1385 carotid plaques following endarterectomies, finding a correlation between larger more calcified plaques among the elderly. They showed that plaque stability decreased with age. Consequently, the endovascular risk during mechanical thrombolysis in the elderly may be higher than in the general population. In our patient group, two patients died as a result of intraoperative rupture following balloon angioplasty of the distal cervical ICA. Despite the advanced age in our series, our combined morbidity and mortality of 27.5% in the practice of multimodal recanalization did not differ significantly from that reported in younger patients.9 Mathews et al42 reviewed 94 consecutive patients who underwent endovascular therapy after ischemic stroke and found a combined morbidity and mortality of 26.6%. Again, given the lack of standardization in new interventional techniques, comparing results across studies poses a challenge.

On discharge, 17 patients (33%) had an mRS score of equal or less than 3, compared with 29% and 16% found by Loh18 and Qureshi20 on discharge, respectively. While the mean age of the patient population was >80 years, 17 patients were between the ages of 75 and 80 years. As our series had equivalent to better outcomes than those previously reported, this potential bias should be noted. In fact, we felt that choosing an arbitrary cut-off of 75 as opposed to 80 years would provide a larger patient population for study. The number of patients older than 80 years (n=34) still comprises 67% of our patient population and therefore the results should be easily compared with existing studies.

General anesthesia during acute stroke intervention is standard practice at our institution at present. Recent literature raises the concern that general anesthesia may worsen neurologic outcomes, or even increase morbidity and mortality, compared with conscious sedation for endovascular recanalization.43 ,44 However, these observations were reported by retrospective studies and thus require confirmation by large prospective randomized studies. Our study has some limitation pertaining to its retrospective design and the absence of a control group (younger patients). We recognize that given the increased risks associated with endovascular treatment in this age group and the strict inclusion criteria for intervention, the patient population is rather small. Assessing outcome at discharge may also not reflect ultimate patient outcome. As mentioned previously, given the single institutional nature of this study, results are interpretable mainly to specific protocols utilized at this institution. Use of angioplasty and stenting must also be considered when interpreting results. Larger prospective randomized studies are required to investigate acute stroke interventions in this patient population, as little exists in the literature.