Interventional Stroke Therapies in the Elderly: Are We Helping?

Discussion

Several important findings are revealed by this study. Patients 75 years or older are being treated less frequently with endovascular interventions compared with younger patients. Lower rates of intervention were not due to later hospital arrival but may reflect lower preadmission functional status. This supposition is supported by a lower mBI in older patients compared with younger patients undergoing an intervention. In addition, treatment guidelines, patient and care provider preference, as well as difficult-to-quantify social factors may explain the different intervention rates. Advanced directives indicating no aggressive therapies or a higher rate of widowed patients lacking a health advocate may also have played a role. In contrast to previous reports of decreased rates and aggressiveness of stroke interventions and diagnostic testing in women,²⁵ we found no sex differences in endovascular treatment rates in this study.

Higher rates of SICH in patients 75 years or older appeared to contribute to increased mortality in this cohort, given the high 89% mortality rate associated with SICH. The increased SICH rate in patients 75 years or older may be related to a higher rate of cardioembolic stroke from atrial fibrillation and to the increased use of warfarin.²⁶ Although we found no significant difference in INR levels between age groups, the mechanism of warfarin-related bleeding may occur via pathways not reflected by INR levels.²⁷ Lower LDL levels have been shown to increase the risk of ICH²⁸ and may contribute to SICH in older patients with stroke undergoing catheter-based interventions. The increased prevalence of hypertension among older patients is likely to contribute to SICH. Higher stroke severity, as measured by an increased NIHSS score, is a well-recognized risk factor for SICH following both IV²⁹ and endovascular procedures.⁸ Although the NIHSS score was significantly higher in the complete older cohort compared with the younger group (Table 1), the NIHSS score was not significantly higher in the older intervention group compared with the younger group (Table 2), possibly due to a ceiling effect.

Because the number of patients receiving IV tPA before the endovascular procedure was similar for both age groups, it is unlikely that larger tPA doses contributed to higher SICH in the older cohort. Time from stroke onset to treatment was similar in the older age group; therefore, delay in providing treatment did not contribute to the increased rate of SICH or mortality. We initially hypothesized that intervention times in older subjects would be prolonged due to increased vessel tortuosity and atherosclerotic burden³⁰; however, the procedure durations were surprisingly shorter for older patients, making it less likely that the increased SICH rates were secondary to higher rates of iatrogenic vessel injury. Lower recanalization rates could also potentially prolong ischemic duration and increase infarct size, leading to higher ICH rates,¹⁹ but the 75-year-or-older cohort had equivalent, if not slightly better, recanalization rates than the younger group. Previous studies have also reported similar recanalization rates in the old compared with the young groups.³¹ Age-related changes such as increased incidence of amyloid angiopathy,^13,32 blood-brain barrier dysfunction,¹⁵ reduced tPA clearance,¹⁴ and impaired clotting mechanisms,¹⁶ which have been previously described, could have predisposed the older patients to ICH.

Because the SICH rate in the younger cohort was similar to that seen in other studies,³³ it is unlikely that the significant increase in SICH rate in the aged is secondary to an unexpected low rate of SICH in the young cohort. The predisposition of the aging brain to bleeding may be more evident in the extended therapeutic window for IA therapies than it is for the more stringent timeframe used for IV therapy. In a recent study by Brinjikji et al,³⁴ no increase in SICH was seen in older patients undergoing interventions, and a lower mortality (29.7%) than that found in our study (46%) was seen, very likely due to their lower chosen age cutoff of 65 years. We chose age 75 on the basis of the HIAT score, shown to be predictive of outcome.⁸ SICH rates remained significantly elevated even when dichotomizing with an age cutoff of 80 years.

Increased medical comorbidities and lower prestroke functional status may also contribute to the high mortality in older interventional patients. Patients 75 years or older may be less tolerant of the general anesthesia induced during IA procedures,^35,36 which is routine for any device interventions at our center. The 2-fold increase in mortality in the older patients was independent of the technique of interventional treatment (IA/device/combination and so forth). Aggressive treatments for AIS such as hemicraniectomy, which are not performed in older patients, may be influencing survival as well. A similarly high mortality rate following interventions in elderly patients with AIS was demonstrated by other studies.^7,31,37

Favorable recanalization rates following IA procedures may explain the comparable improvement in NIHSS scores between admission and discharge in both age groups (Table 3). Although older patients had a similar rate of improvement in NIHSS score at discharge after intervention, the functional benefit appears to end there for older patients with AIS (Table 4). In younger patients, the proportion of favorable mBI continues to improve (to 52% at 12 months), whereas recovery stopped after 3 months in our older cohort. This finding has implications for rehabilitation approaches following stroke in older adults. Studies have shown decreased neuroplasticity in the aging brain, which may limit the extent of recovery,³⁸ though it is also possible that older adults are not receiving the full extent of rehabilitative services to reach their potential. Our findings are consistent with prior studies that have found worse functional outcomes in older adults.^31,39,40

Our study has several limitations and these data must be interpreted with these in mind. This was a single-center retrospective analysis. However, it is one of the largest cohorts that has been examined to date and has the longest follow-up (12 months) compared with currently published data. The decision to administer treatment was not randomized, and a bias exists toward selecting older patients with better premorbid functional status. However, the prestroke mBI was significantly lower in the older patients, suggesting that there were meaningful baseline deficits in the older cohort. Perfusion scans were not performed to guide patient selection. Recent studies have indicated that the extent of perfusion deficits may indicate risk of hemorrhagic transformation.⁴¹ The high mortality rate in the older age group makes analysis of long-term functional outcomes susceptible to selection bias. We did not distinguish between anterior and posterior circulation strokes or the different types of recanalization methods (due to the small numbers). IA tPA and mechanical clot disruption were grouped together for both young and old groups, so it was a less likely source of bias. In addition, during the 4-year study period, new catheter devices emerged¹² adding variability to the interventions, which may have altered observed outcomes. Previous studies have failed to show a significant difference in the complication rate based on the type of procedure.¹⁸ Information on the degree of recanalization was not defined by TIMI guidelines.⁴² Rather “successful” revascularization was determined by the interventional neuroradiologist and was equivalent to a TIMI flow of II or above.

Decisions regarding endovascular treatment for the older patients with AIS are often made on an individual basis and can be influenced by many factors, including baseline functional status, time of onset, stroke severity, patient and family preferences, imaging criteria, and ethical considerations. Our findings of higher SICH and mortality in patients 75 years or older make future studies examining the selection criteria for interventional therapies essential. The optimal form of anesthesia and sedation, especially in the older age group, is an important area of investigation. High rates of recanalization and improved neurologic function during the course of hospitalization suggest that some older patients are appropriate candidates for endovascular stroke treatments, offering an alternative to those who do not qualify for respond to IV thrombolysis. The high mortality in the elderly undergoing endovascular procedures likely stems from comorbid factors, medical complications, and the increased rate of SICH. Strategies to improve long-term recovery to maintain the rate of recovery during the hospitalization also need to be explored. Prospective randomized trials are needed to determine criteria for selecting elderly patients with stroke most likely to benefit from acute endovascular stroke therapies, including the use of perfusion imaging.