Efficacy of IAT in elderly requires further study

Joshua A. Hirsch, ,

Other Contributors:

August 27, 2012

We salute Dr. Ghobrial and colleagues for their important contribution regarding the endovascular management of elderly ischemic stroke patients.1 Although this topic is relatively new to the literature, it is of critical importance to the field of intra-arterial therapy (IAT) given the increasing use of catheter-based stroke therapies2 and the expanding population of elderly Americans, who are at the highest risk for ischemic stroke.

The authors conducted an extensive, retrospective single-center study using chart review that identified elderly patients (aged ?75years) that underwent IAT between 2006-2012. The minimum NIHSS score used in this analysis was 8, and patients were selected using NCCT between 2006-2009, and from 2009 onwards, additional CTA and CTP studies were performed. The recanalization rate (TIMI 2-3) was 65% with symptomatic intracranial hemorrhage occurring in 6%. All-cause mortality was 22% with two deaths from intra-operative vessel rupture. The average discharge mRS score was 3.9 and overall 33% of elderly patients achieved favorable outcome (mRS 0- 3). The authors have concluded that "multimodal endovascular management of acute ischemic stroke in patients over 75 years old is safe and effective".

In our view, these results warrant a more cautious conclusion than the one advocated in in the manuscript. The natural question is "safe and effective" compared to what? Is it as safe and effective as treatment in a younger cohort? To answer this question, a comparison with a concurrent population of younger patients treated with IAT at the same center would be necessary, although this was not performed. Is it as safe and effective as IV tPA or best medical management? Such control groups were not studied. The reader is left to compare these results with those of other centers. However, as the authors state in their discussion, comparing treatment outcomes between centers is complicated by varying patient selection criteria and treatment algorithms. Similarly, the definitions of outcomes vary significantly between the studies and ultimately prevent between-center comparisons.

In the growing body of literature on IAT and post-stroke outcomes in the elderly, there are no randomized controlled data evaluating IAT efficacy versus IV tPA or best medical management. Most papers, including a recent retrospective study from our group, report treatment results between elderly and non-elderly cohorts treated concurrently in the same center.3-7 These papers suggest that there are similar rates of revascularization and significant reperfusion hemorrhage between the two age groups. This last point supports that IAT is safe in older patients. However, mortality is also significantly increased in the elderly cohort.

Most interestingly, achieving functional independence (mRS 0-2) at 90 -days post-stroke by the elderly ranges greatly from 0 to ~45%. In our paper, we suggest that this may be related in part to differences in baseline health and disability status among the older patients. This is supported by the prior reports of co-morbidities influencing IAT outcomes in the Merci and Multi-Merci trials.8 Furthermore, a separate analysis from our institution demonstrated that pre-stroke dementia is an independent predictor of poor outcomes in the elderly.9 On the other hand, high variability in the post-stroke outcomes in the elderly allows for a possibility that a certain subset of elderly patients may benefit from this treatment; however, more data are needed to clarify this question.

Until prospective, systematically collected data are available, though, what approach should we advocate for in the elderly patients who are otherwise eligible for acute stroke intervention? We previously reported on a institutional protocol developed and implemented by our multidisciplinary Acute Stroke Service (Stroke Neurology and NeuroInterventional services) that aims to stratify acute stroke patients into groups that are most likely, uncertain or unlikely to benefit from IAT based on established predictors of outcome after catheter-based therapy.10 Future modifications to this algorithm including the emerging data on age and dementia will be incorporated and studied prospectively and in a systematic way in order assess on the effects of novel determinants of post-stroke outcomes in IAT patients.

Because outcomes data are conflicting and because some elderly patients may regain independence after IAT, such patients should not be excluded from consideration for treatment. Furthermore, our existing patient-selection algorithm may change after greater clinical experience with stentrievers, as the greater degree and speed of reperfusion afforded by this technology may particularly benefit the elderly population, who may have reduced neuronal reserve compared to younger patients. However this is a theoretical consideration at this time, pending accumulation of further experience and data.

Overall, based on the accumulated evidence, it is reasonable to conclude that IAT is safe in the elderly. However, any conclusion regarding its effectiveness remains premature and will require further study.

References

1. Ghobrial GM, Chalouhi N, Rivers L, et al. Multimodal endovascular management of acute ischemic stroke in patients over 75 years old is safe and effective. J Neurointerv Surg. 2012.

2. Hirsch JA, Yoo AJ, Nogueira RG, et al. Case volumes of intra- arterial and intravenous treatment of ischemic stroke in the USA. J Neurointerv Surg. 2009;1(1):27-31.

3. Chandra RV, Leslie-Mazwi TM, Oh DC, et al. Elderly Patients Are at Higher Risk for Poor Outcomes After Intra-Arterial Therapy. Stroke. 2012.

4. Mono M-L, Romagna L, Jung S, et al. Intra-Arterial Thrombolysis for Acute Ischemic Stroke in Octogenarians. Cerebrovasc Dis. 2012;33(2):116-122.

5. Qureshi AI, Suri MFK, Georgiadis AL, Vazquez G, Janjua NA. Intra- Arterial Recanalization Techniques for Patients 80 Years or Older with Acute Ischemic Stroke: Pooled Analysis from 4 Prospective Studies. AJNR Am J Neuroradiol. 2009;30(6):1184-1189.

6. Loh Y, Kim D, Shi ZS, et al. Higher Rates of Mortality but Not Morbidity Follow Intracranial Mechanical Thrombectomy in the Elderly. AJNR Am J Neuroradiol. 2010;31(7):1181-1185.

7. Kim D, Ford GA, Kidwell CS, et al. Intra-arterial thrombolysis for acute stroke in patients 80 and older: a comparison of results in patients younger than 80 years. AJNR Am J Neuroradiol. 2007;28(1):159-163.

8. Flint AC, Duckwiler GR, Budzik RF, Liebeskind DS, Smith WS, for the MERCI and Multi MERCI Writing Committee. Mechanical Thrombectomy of Intracranial Internal Carotid Occlusion: Pooled Results of the MERCI and Multi MERCI Part I Trials. Stroke. 2007;38(4):1274-1280.

9. Busl KM, Nogueira RG, Yoo AJ, Hirsch JA, Schwamm LH, Rost NS. Prestroke Dementia is Associated with Poor Outcomes after Reperfusion Therapy among Elderly Stroke Patients. J Stroke Cerebrovasc Dis. 2011.

10. Rost NS, Smith EE, Nogueira RG, et al. Implementation of a patient selection protocol for intra-arterial therapy increases treatment rates in patients with acute ischemic stroke. J Neurointerv Surg. 2012.

Conflict of Interest:

None declared

Conflict of Interest

None declared