We would like to thank Dr Hirsch and colleagues from Massachusetts
General Hospital for their insightful comment on our paper.1 The authors
advocate a more cautious conclusion regarding the efficacy of endovascular
stroke intervention in the elderly since a control group of younger
patients is lacking in our study. Although comparison to a younger group
of patients is interesting, such data can hardly be used for drawing
definitive conclusions regarding the efficacy of endovascular therapy. A
clinical comparison between young and older patients is unfortunately not
possible due to tremendous differences between the two study populations,
such as pre-existing medical comorbidities and dementia. Randomized
controlled studies comparing patient outcomes with intra-arterial therapy
versus intravenous thrombolysis or best medical management will be needed
to provide definitive information on the best therapeutic approach in this
patient population.
In patients with NIHSS of 8 or above who have failed or were not
eligible for intravenous thrombolysis, such as in our study population,
medical therapy is unfortunately limited to supportive management. Most of
these patients are destined to end of life care or are neurologically
devastated from their stroke. In an era of FDA-approved intra-arterial
thrombolysis, there is an ethical dilemma in randomizing patients that
meet criteria to such life-saving interventions to medical therapies,
regardless of their age group. It is therefore extremely challenging to
obtain level-one evidence data in the elderly or any other age population
comparing medical and endovascular stroke therapies.
Timely recanalization in acute ischemic stroke improves patient
outcomes.2-4 Arterial recanalization can be achieved by intravenous or
intraarterial means. Evidence suggests that treatment benefit with
intravenous tissue plasminogen activator (IV-tPA) extends to patients
older than 80 years.5 It is therefore plausible that intra-arterial
thrombolysis could confer a similar benefit in elderly patients. In our
study, almost a third of elderly patients achieved favorable outcomes with
intraarterial thrombolysis, and similar rates were also reported by other
investigators.6-7 In our opinion, such rates can be regarded as
satisfactory considering the compromised collateral circulation, the
reduced neuronal reserve, as well as the high frequency of pre-stroke
comorbid conditions in this age group. However, we agree with Dr Hirsch
and colleagues that this would require further confirmation by prospective
controlled data.
In a recently published study by Chandra and colleagues8 from
Massachusetts General Hospital, 49 elderly and 130 nonelderly patients
treated between 2005 and 2010 were rigorously compared with respect to
angiographic reperfusion, rate of parenchymal hematoma, and 90-day
clinical outcome. The authors report comparable rates of reperfusion and
hemorrhage between the two groups but favorable outcomes in only 2% of
elderly patients and conclude that recanalization in this group "may be
futile". In our view, these results warrant a more cautious conclusion
than the one advocated in their report not only because comparison to a
control group treated with medical therapy is lacking but also for the
following reasons. 1) Nearly 33% of elderly patients in their study were
disabled at baseline (mRS score 2 or greater), which makes the prospect of
a favorable outcome nearly impossible in as many as one-third of their
cohort. 2) Medical care was withdrawn in 55% of elderly patients, which
obviously complicates any assessment of outcome. 3) CT perfusion data was
not used to select patients for acute stroke intervention, which could
possibly suggest that some patients with little or no salvageable brain
tissue may have undergone endovascular treatment. In fact, CT perfusion
can optimize patient selection for endovascular recanalization based on an
individual's physiological parameters rather than an arbitrary time frame
and may be of greater value in this specific population by helping
identify "the subset of elderly patients who may benefit" from treatment.9
-11
Finally, we agree with Dr Hirsch and colleagues that endovascular
stroke intervention in elderly patients is safe. Although the question of
its efficacy requires more investigation, we believe that elderly patients
should not be excluded from consideration for treatment especially if
perfusion studies indicate adequate penumbra. The significance of proper
patient selection for endovascular recanalization cannot be overstressed.
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. Jul 11 2012.
2.Meyers PM, Schumacher HC, Connolly ES, Jr., Heyer EJ, Gray WA,
Higashida RT. Current status of endovascular stroke treatment.
Circulation. Jun 7 2011;123(22):2591-2601.
3.Tissue plasminogen activator for acute ischemic stroke. The
National Institute of Neurological Disorders and Stroke rt-PA Stroke Study
Group. N Engl J Med. Dec 14 1995;333(24):1581-1587.
4.Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3
to 4.5 hours after acute ischemic stroke. N Engl J Med. Sep 25
2008;359(13):1317-1329.
5.Mishra NK, Diener HC, Lyden PD, Bluhmki E, Lees KR. Influence of
age on outcome from thrombolysis in acute stroke: a controlled comparison
in patients from the Virtual International Stroke Trials Archive (VISTA).
Stroke. Dec 2010;41(12):2840-2848.
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. Aug 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. Jan 2007;28(1):159-163.
8.Chandra RV, Leslie-Mazwi TM, Oh DC, et al. Elderly Patients Are at
Higher Risk for Poor Outcomes After Intra-Arterial Therapy. Stroke. Jun 28
2012.
9.Abou-Chebl A. Endovascular treatment of acute ischemic stroke may
be safely performed with no time window limit in appropriately selected
patients. Stroke. Sep 2010;41(9):1996-2000.
10.Jovin TG, Liebeskind DS, Gupta R, et al. Imaging-based
endovascular therapy for acute ischemic stroke due to proximal
intracranial anterior circulation occlusion treated beyond 8 hours from
time last seen well: retrospective multicenter analysis of 237 consecutive
patients. Stroke. Aug 2011;42(8):2206-2211.
11.Natarajan SK, Snyder KV, Siddiqui AH, Ionita CC, Hopkins LN, Levy
EI. Safety and effectiveness of endovascular therapy after 8 hours of
acute ischemic stroke onset and wake-up strokes. Stroke. Oct
2009;40(10):3269-3274.
Conflict of Interest:
None declared
We would like to thank Dr Hirsch and colleagues from Massachusetts General Hospital for their insightful comment on our paper.1 The authors advocate a more cautious conclusion regarding the efficacy of endovascular stroke intervention in the elderly since a control group of younger patients is lacking in our study. Although comparison to a younger group of patients is interesting, such data can hardly be used for drawing definitive conclusions regarding the efficacy of endovascular therapy. A clinical comparison between young and older patients is unfortunately not possible due to tremendous differences between the two study populations, such as pre-existing medical comorbidities and dementia. Randomized controlled studies comparing patient outcomes with intra-arterial therapy versus intravenous thrombolysis or best medical management will be needed to provide definitive information on the best therapeutic approach in this patient population.
In patients with NIHSS of 8 or above who have failed or were not eligible for intravenous thrombolysis, such as in our study population, medical therapy is unfortunately limited to supportive management. Most of these patients are destined to end of life care or are neurologically devastated from their stroke. In an era of FDA-approved intra-arterial thrombolysis, there is an ethical dilemma in randomizing patients that meet criteria to such life-saving interventions to medical therapies, regardless of their age group. It is therefore extremely challenging to obtain level-one evidence data in the elderly or any other age population comparing medical and endovascular stroke therapies.
Timely recanalization in acute ischemic stroke improves patient outcomes.2-4 Arterial recanalization can be achieved by intravenous or intraarterial means. Evidence suggests that treatment benefit with intravenous tissue plasminogen activator (IV-tPA) extends to patients older than 80 years.5 It is therefore plausible that intra-arterial thrombolysis could confer a similar benefit in elderly patients. In our study, almost a third of elderly patients achieved favorable outcomes with intraarterial thrombolysis, and similar rates were also reported by other investigators.6-7 In our opinion, such rates can be regarded as satisfactory considering the compromised collateral circulation, the reduced neuronal reserve, as well as the high frequency of pre-stroke comorbid conditions in this age group. However, we agree with Dr Hirsch and colleagues that this would require further confirmation by prospective controlled data.
In a recently published study by Chandra and colleagues8 from Massachusetts General Hospital, 49 elderly and 130 nonelderly patients treated between 2005 and 2010 were rigorously compared with respect to angiographic reperfusion, rate of parenchymal hematoma, and 90-day clinical outcome. The authors report comparable rates of reperfusion and hemorrhage between the two groups but favorable outcomes in only 2% of elderly patients and conclude that recanalization in this group "may be futile". In our view, these results warrant a more cautious conclusion than the one advocated in their report not only because comparison to a control group treated with medical therapy is lacking but also for the following reasons. 1) Nearly 33% of elderly patients in their study were disabled at baseline (mRS score 2 or greater), which makes the prospect of a favorable outcome nearly impossible in as many as one-third of their cohort. 2) Medical care was withdrawn in 55% of elderly patients, which obviously complicates any assessment of outcome. 3) CT perfusion data was not used to select patients for acute stroke intervention, which could possibly suggest that some patients with little or no salvageable brain tissue may have undergone endovascular treatment. In fact, CT perfusion can optimize patient selection for endovascular recanalization based on an individual's physiological parameters rather than an arbitrary time frame and may be of greater value in this specific population by helping identify "the subset of elderly patients who may benefit" from treatment.9 -11
Finally, we agree with Dr Hirsch and colleagues that endovascular stroke intervention in elderly patients is safe. Although the question of its efficacy requires more investigation, we believe that elderly patients should not be excluded from consideration for treatment especially if perfusion studies indicate adequate penumbra. The significance of proper patient selection for endovascular recanalization cannot be overstressed.
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. Jul 11 2012.
2.Meyers PM, Schumacher HC, Connolly ES, Jr., Heyer EJ, Gray WA, Higashida RT. Current status of endovascular stroke treatment. Circulation. Jun 7 2011;123(22):2591-2601.
3.Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. Dec 14 1995;333(24):1581-1587.
4.Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. Sep 25 2008;359(13):1317-1329.
5.Mishra NK, Diener HC, Lyden PD, Bluhmki E, Lees KR. Influence of age on outcome from thrombolysis in acute stroke: a controlled comparison in patients from the Virtual International Stroke Trials Archive (VISTA). Stroke. Dec 2010;41(12):2840-2848.
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. Aug 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. Jan 2007;28(1):159-163.
8.Chandra RV, Leslie-Mazwi TM, Oh DC, et al. Elderly Patients Are at Higher Risk for Poor Outcomes After Intra-Arterial Therapy. Stroke. Jun 28 2012.
9.Abou-Chebl A. Endovascular treatment of acute ischemic stroke may be safely performed with no time window limit in appropriately selected patients. Stroke. Sep 2010;41(9):1996-2000.
10.Jovin TG, Liebeskind DS, Gupta R, et al. Imaging-based endovascular therapy for acute ischemic stroke due to proximal intracranial anterior circulation occlusion treated beyond 8 hours from time last seen well: retrospective multicenter analysis of 237 consecutive patients. Stroke. Aug 2011;42(8):2206-2211.
11.Natarajan SK, Snyder KV, Siddiqui AH, Ionita CC, Hopkins LN, Levy EI. Safety and effectiveness of endovascular therapy after 8 hours of acute ischemic stroke onset and wake-up strokes. Stroke. Oct 2009;40(10):3269-3274.
Conflict of Interest:
None declared