We thank the authors for their letter entitled, "Caution during use
of DDAVP in IPSS," by Drs. Pecori Giraldi, Federici, and Cavagnini. The
authors suggest that because of the hypercoagulable state that
characterizes Cushing disease, DDAVP may not be safe since it has been
shown to increase the level of von Willebrand factor (vWF) and could
therefore lead to platelet adhesion and cause thromboembolism...
We thank the authors for their letter entitled, "Caution during use
of DDAVP in IPSS," by Drs. Pecori Giraldi, Federici, and Cavagnini. The
authors suggest that because of the hypercoagulable state that
characterizes Cushing disease, DDAVP may not be safe since it has been
shown to increase the level of von Willebrand factor (vWF) and could
therefore lead to platelet adhesion and cause thromboembolism. The authors
point to their own published work suggesting this effect (1). In this
paper, the authors show that not only vWF levels increase, but also t-PA,
likely to achieve a balance by activating fibrinolytic pathways.
Therefore, increased risk of thromboembolic events in Cushing disease
patients in the context of DDAVP administration is a theoretical
consideration.
Thromboembolism is a rare complication of BIPSS and when reported,
has been linked to lack of prophylaxis with IV heparin (2, 3). In our
practice, we routinely heparinize patients undergoing BIPSS, whether they
receive CRH or DDAVP to stimulate the pituitary (4). The case series
previously reported where DDAVP was used rather than CRH do not indicate
an increased risk of thromboembolic events (5-8). As the increased risk of
thromboembolism is only a theoretical consideration, we can only use this
available clinical data. Because the sensitivity of BIPSS is significantly
increased by the use of CRH or DDAVP, the benefits of using DDAVP appear
at this point to outweigh the theoretical risks. One possible positive
outcome of the CRH shortage is that more data will be accumulated to
determine whether there are unexpected negative effects of using DDAVP.
1. Pecori Giraldi F, Ambrogio AG, Fatti LM, Rubini V, Cozzi G,
Scacchi M et al. Von Willebrand factor and fibrinolytic parameters during
the desmopressin test in patients with Cushing's disease. Br.J.Pharmacol.
2011;71:132-6.
2. Blevins LS Jr, Clark RV, Owens DS. Thromboembolic complications
after inferior petrosal sinus sampling in patients with Cushing's
syndrome. Endocr Pract 1998; 4:365-367.
3. Obuobie K, Davies JS, Ogunko A, Scanlon MF. Venous thrombo-
embolism following inferior petrosal sinus sampling in Cushing's disease.
J Endocrinol Invest 2000; 23:542-544.
4. Deipolyi...Oklu et al. The role of bilateral inferior petrosal
sinus sampling in the diagnostic evaluation of Cushing syndrome. Diagn
Interv Radiol 2012; 18:132-138
5. Castinetti F, Morange I, Dufour H, et al. Desmopressin test during
petrosal sinus sampling: a valuable tool to discriminate pituitary or
ectopic ACTH-dependent Cushing's syndrome. Eur J Endocrinol 2007;157:271-
7.
6. Machado MC, de Sa SV, Domenice S, et al. The role of desmopressin
in bilateral and simultaneous inferior petrosal sinus sampling for
differential diagnosis of ACTH-dependent Cushing's syndrome. Clin
Endocrinol (Oxf) 2007;66:136-42.
7. Malerbi DA, Mendonca BB, Liberman B, et al. The desmopressin
stimulation test in the differential diagnosis of Cushing's syndrome. Clin
Endocrinol (Oxf) 1993;38:463-72.
8. Salgado LR, Mendon??a BB, Pereira MAA, et al. Use of Desmopressin
in Bilateral and Simultaneous Inferior Petrosal Sinus Sampling for
Differential Diagnosis of ACTH-Dependent Cushing's Syndrome. The
Endocrinologist 1997;7:135-40.
Dear Sir,
we have read with great interest the paper by Deipolyi and co-workers on
the use of desmopressin during inferior petrosal sinus sampling (IPSS) in
alternative to corticotropin-releasing hormone (CRH) for the diagnostic
work-up of Cushing's disease (1). As the Authors report, evidence
collected in small series suggests that desmopressin achieves an
equivalent diagnostic accuracy to CRH, thus appears a tempting...
Dear Sir,
we have read with great interest the paper by Deipolyi and co-workers on
the use of desmopressin during inferior petrosal sinus sampling (IPSS) in
alternative to corticotropin-releasing hormone (CRH) for the diagnostic
work-up of Cushing's disease (1). As the Authors report, evidence
collected in small series suggests that desmopressin achieves an
equivalent diagnostic accuracy to CRH, thus appears a tempting and less
expensive alternative. It is worth recalling, however, that desmopressin
is also a potent haemostatic agent and that patients with Cushing's
syndrome are at increased risk for thromboembolic events (2), some even
occuring during IPSS performed at expert centers (3). In this context, we
have recently observed that endothelial factors are released upon
administration of desmopressin to patients with Cushing's disease (4),
although the dose used for diagnostic purposes is roughly half the
haemostatic dosage. The magnitude of the increase in von Willebrand
factor, a promoter of platelet adhesion to the subendothelium in the early
phases of haemostasis, was comparable to the one observed in healthy
subjects and possibly counterbalanced by increased fibrinolytic factors
but to what extent these changes might affect general haemostatic
processes remains to be ascertained. As a consequence, as long as no
further evidence is available on the safety of this haemostatic agent
during endovascular damages, procedures which are per se at risk for
vascular events, extreme caution should be exercised when using
desmopressin instead of CRH during IPSS.
References
1. Deipolyi AR, Hirsch JA, Oklu R. Bilateral inferior petrosal sinus
sampling with desmopressin. J.Neurointervent.Surg.
2012;doi10.1136/neurointsurg-2012-010437.
2. Stuijver DJF, van Zaane B, Feelders RA, Debeij J, Cannegieter SC,
Hermus AR et al. Incidence of venous thromboembolism in patients with
Cushing's syndrome: a multicenter cohort study. J.Clin.Endocrinol.Metab.
2011;96:3525-32.
3. Doppman JL. There is no simple answer to a rare complicaton of inferior
petrosal sinus sampling. Am.J.Neuroradiology 1999;20:191-2.
4. Pecori Giraldi F, Ambrogio AG, Fatti LM, Rubini V, Cozzi G, Scacchi M
et al. Von Willebrand factor and fibrinolytic parameters during the
desmopressin test in patients with Cushing's disease. Br.J.Pharmacol.
2011;71:132-6.
The reply from Perez et al to my letter of March 2012 is misleading
and wrong in two important regards.1 First, they state that their report
of the use of the solitaire stent for thrombectomy was just a case report,
"nothing else". 2 This is not true. In fact, they explicitly use this
report, both in the abstract and conclusion to lay claim for developing
the stentreiever concept for thrombectomy: "This was the first...
The reply from Perez et al to my letter of March 2012 is misleading
and wrong in two important regards.1 First, they state that their report
of the use of the solitaire stent for thrombectomy was just a case report,
"nothing else". 2 This is not true. In fact, they explicitly use this
report, both in the abstract and conclusion to lay claim for developing
the stentreiever concept for thrombectomy: "This was the first .. use of
the Solitaire stent for this purpose and the ignition spark for the
development of a whole new generation of devices". In addition, this
report was titled a "Historical Vignette". This report was written to
take credit for the development of stentreivers for acute stroke. To
state, as they do in their response to my letter, that their paper makes
no claims is clearly disingenuous.
Second, they dismiss the idea that the prior publication by Kelly et
al -- reporting the use of an Enterprise stent (Codman Neurovascular,
Rayhnam, MA) as a temporary endovascular bypass to achieve successful
revascularization in a patient with an acute ischemic stroke and large
vessel occlusion -- had any influence on their work. This claim is
disingenuous as well. In their response, they state that " ... temporary
bypass might have been a local and ephemeral phenomenon; however it did
not cause to much commotion, at least in Europe." However, the technique
of stent-retrieval, or any kind of temporary stenting for acute stroke is,
in fact, part and parcel of "temporary endovascular bypass". The best
evidence of this is that the authors presented their own original
experience with the Solitaire at the 2010 International Stroke Conference
in an abstract entitled "Temporary Endovascular Bypass for the treatment
of ischemic stroke: Experience After 50 Patients". Clearly their work
with the Solitaire stent in acute stroke was influenced by this prior
report.
In summary, despite their claims, the concept of temporary stenting
for acute stroke treatment preceded the authors' 2008 case. In their
Historical Vignette and subsequent response to my prior letter, the
authors are attempting to rewrite history. They do deserve credit for
taking this concept and rapidly moving it forward in clinical practice,
however.
References:
1. Re: Perez et al 'Intracranial thrombectomy using the Solitaire stent: a
historical vignette'. Derdeyn CP. J Neurointerv Surg. 2012 Mar;4(2):153-4;
Author Response 154
2. Intracranial thrombectomy using the Solitaire stent: a historical
vignette. P?rez MA, Miloslavski E, Fischer S, B?zner H, Henkes H. J
Neurointerv Surg. 2011 Dec 14.
3. Kelly ME, Furlan AJ, Fiorella D. Recanalization of an acute middle
cerebral artery occlusion using a self-expanding, reconstrainable,
intracranial microstent as a temporary endovascular bypass. Stroke
2008;39:1770-3.
4. Liebig T, Lockau H, Stehle S, Dorn F, Prothmann S, Henkes HH. Temporary
Endovascular Bypass in Acute Stroke: Experience After 50 Patients. Stroke
2010 Vol 41,1:e259-260.
We would like to add our strong support to the recent editorial by
Fiorella, et al. Dr. Fiorella and his colleagues should be congratulated
for pointing out the giant elephant in the room. The government, insurers
and patients are increasingly demanding more quality, safety and value
from the healthcare dollar and, like it or not, we can no longer ignore
their pleas. Dr. Fiorella has eloquently shown us with widely ava...
We would like to add our strong support to the recent editorial by
Fiorella, et al. Dr. Fiorella and his colleagues should be congratulated
for pointing out the giant elephant in the room. The government, insurers
and patients are increasingly demanding more quality, safety and value
from the healthcare dollar and, like it or not, we can no longer ignore
their pleas. Dr. Fiorella has eloquently shown us with widely available
data that our profession now has more than enough manpower to handle the
labor demands extending into the foreseeable future. The current trend of
overproducing neurointerventional fellows has already led to decreased
quality and safety and is a profound misallocation of scarce medical
resources. These issues are further compounded by the current lack of a
standardized training curriculum and certifying examination.
One other factor that was not mentioned in the editorial is the
inevitable replacement of the fee for service payment model with bundled
payments or some similar type of payment distribution. It is not a
question of if this change will occur, but rather when it will occur.
Because the procedures we perform are very expensive, our specialty will
be under tremendous scrutiny by the accountable care organizations or
other entities that are tasked with managing and allocating the funds for
these bundled payments. Simply put, this paradigm shift in healthcare
financing will demand that neurointerventionalists intervene only in those
situations that are proven effective and provide value. In a world of
bundled payments, the focus will absolutely be on conservative medical
management rather than complex and expensive interventions. As painful as
it may seem to those of us who perform these procedures, it is inevitable.
We believe this will contribute to declining neurointerventional volumes
in the near future and is why we should halt all neurointerventional
fellowship training until there is adequate volume to maintain expertise
among current practitioners.
Unfortunately, we might be too late to stop this runaway train.
Given the number of fellows currently being trained and the relatively low
rate of retirement from our specialty at this time, we will experience a
glut of neurointerventionalists in the next few years. Because there is
no consistent scrutiny of quality in the neurointerventional fellowships,
there are "puppy mill" fellowships popping up all over the country. These
fellowships do not provide adequate procedure complexity, volume or
oversight to produce even a marginally competent neurointerventionalist.
Sadly, we have seen the recent intrusion of this type of subpar training
program into our medical community with as many as six fellows being
trained simultaneously in community, suburban, nonacademic hospital
facilities. Those of us who practice in the larger, academic, tertiary
referral hospitals are now seeing the unfortunate consequences imposed
upon the patients. The disasters range from procedures that clearly
should have never been attempted, even by experienced operators, to
procedures that are declined due to being "technically difficult" despite
really being rather straightforward and clinically warranted.
Obviously, we are just as passionate about this crisis as Dr.
Fiorella and his long list of distinguished coauthors. While it might be
too late to avert our current crisis, the impact could be dampened if all
future fellows that have not yet started their programs and those that are
considering our profession were to strongly consider these circumstances
and perhaps choose a different subspecialty.
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...
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.
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
isc...
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.
The response from the Stenting and Aggressive Medical Management for
the Prevention of Recurrent Ischemic Stroke (SAMMPRIS) trial principal
investigators (PIs) is greatly appreciated. Healthy debate helps us weed
out the details that are important in these studies and future trial
design. Although the PIs label some of the editorial comments as
"inaccuracies", one could disagree based on the information listed below....
The response from the Stenting and Aggressive Medical Management for
the Prevention of Recurrent Ischemic Stroke (SAMMPRIS) trial principal
investigators (PIs) is greatly appreciated. Healthy debate helps us weed
out the details that are important in these studies and future trial
design. Although the PIs label some of the editorial comments as
"inaccuracies", one could disagree based on the information listed below.
So let's look at the numbers and the facts.
First, they state the SAMMPRIS population was the right population to
test, based on the Warfarin versus Aspirin for Symptomatic Intracranial
Disease (WASID) trial data. However, they base this statement on the
criteria of the degree of stenosis, and some standard, but relatively
artificial epidemiological criteria, not focusing on some other important
clinical criteria. For example, the mean time of enrollment from
qualifying event to enrollment was 17 days in the WASID trial and 7 days
in the SAMMPRIS trial, so these are not exactly the same patient
populations. The patients who were stented in SAMMPRIS within 7 days of
their qualifying event did remarkably worse than the patients stented
after day 7, indicating that either these patients had unstable plaque or
some other factor that increased their risk for complications when treated
early. The Wingspan safety trial that led to FDA approval of the Wingspan
stent did NOT include patients who had stroke less than 7 days, so to
stent patients at less than 7 days from the event was another variable
introduced by the SAMMPRIS trial design that was not a part of the
original Food and Drug Administration (FDA) approval of the stent.
Second, they state that the Wingspan stent was not used off-label.
This is not exactly true. The Investigational Device Exemption (IDE) use
of the Wingspan stent in the SAMMPRIS trial was used for expanded
indications compared to the Humanitarian Device Exemption (HDE) FDA
approval. In fact, this was exactly one of the reasons that an IDE
approval was necessary for the trial. Interestingly, if one analyzes the
presenting symptoms, time to treatment, medical failure, and other
factors, only 8% of the patients enrolled in SAMMPRIS would have qualified
for the original Wingspan safety study upon which the FDA granted approval
(FDA Panel Review, March 2012, Baltimore, MD). Therefore, practices such
as treating patients before day 7 post-event, allowing TIA versus stroke
only as an entry criteria, and allowing patients who had not failed
medical therapy into the trial, were markedly expanded indications for the
stent in this trial. For this reason, one could argue that this trial was
not designed for stenting to succeed. Typically, every device trial is
initially designed for the on-label indication, and only later are there
considerations for expanded indications. This was not the paradigm used
in SAMMPRIS. In the subgroup of the 8% of patients in SAMMPRIS that
actually would have qualified for the original Wingspan safety trial,
there was no statistical difference in clinical outcomes between the
stenting and the medical therapy groups.
Third, the argument that even the subgroup of patients who previously
failed anti-platelet therapy did worse with stenting than medical therapy
is easily predictable, if you look how stented patient were managed in the
study. Many major centers test patients for anti-platelet therapy
resistance prior to stent placement, since there is a documented 15%
relative clopidogrel resistance in the population and 10% aspirin
resistance. Patients who are resistant to anti-platelet therapy are more
likely to have a thromboembolic event with a fresh stent placement, as a
nidus for platelet aggregation than someone with a chronic atherosclerotic
stenosis. The SAMMPRIS trial failed to account for possible anti-platelet
therapy resistance as many coronary stenting trials current address. In
fact, it was a protocol violation in SAMMPRIS even to measure the anti-
platelet therapy resistance.
Finally, the argument that interventionalist experience did not play
a role in the results is very short-sighted and is based on poorly
stratified data. It would be difficult to believe that anyone would argue
that less experienced stenters could have equivalent clinical results than
more experienced stenters. The average number of Wingspan stents placed
by interventionalists to qualify as a stenter in the study was 10 Wingspan
stents. This low number, as a distinction between low and high volume
stenters, would not be acceptable in any current stenting trial:
coronary, carotid, peripheral, etc. So technically, both "low volume" and
"high volume" groups analyzed by the PIs were low volume users.
The goals for the future should be to focus our attention on defining
which population will benefit most with revascularization, what is the
best timing for the procedure, and what medical therapy regimen is best
for patients with newly placed intracranial stents, which may not be the
same as the best therapy for those without stents. SAMMPRIS gives a
significant amount of information, but it is a starting point, not an end
to this therapy.
Conflict of Interest:
Dr. Alexander was an investigator in the SAMMPRIS clinical trial. He is a device proctor and consultant for Styker Neurovascular which manufactures the Wingspan stent.
As the Principal Investigators for the Stenting and Aggressive
Medical Management for the Prevention of Recurrent Ischemic Stroke
(SAMMPRIS) trial, we are compelled to address a few inaccuracies regarding
this study in the recent editorial by Dr. Alexander.
The first point is the patient population. The SAMMPRIS population
was the right patient population to test. We had very good data from the
Warfarin vers...
As the Principal Investigators for the Stenting and Aggressive
Medical Management for the Prevention of Recurrent Ischemic Stroke
(SAMMPRIS) trial, we are compelled to address a few inaccuracies regarding
this study in the recent editorial by Dr. Alexander.
The first point is the patient population. The SAMMPRIS population
was the right patient population to test. We had very good data from the
Warfarin versus Aspirin for Symptomatic Intracranial Disease (WASID) trial
that patients with recently symptomatic severe stenosis were at the
highest risk for recurrent stroke 1. This high risk population offered
the best chance for showing a benefit with revascularization. Much of
the criticism in the editorial has the benefit of hindsight. The
hemodynamic versus embolic mechanisms for stroke may be important in
defining groups that benefit from angioplasty in the future 2. This
distinction does not matter for extracranial carotid disease, as
revascularization works regardless of mechanism. It may matter for
intracranial atherosclerotic disease. Finally, in designing a trial,
there are always groups of patients that will not be included, such as the
high risk unstable patients described in the editorial. Our data does not
address treatment of these patients one way or the other and that should
not be a criticism of the trial.
Second, the Wingspan stent was not used off-label in the trial. It
is true that we used the stent under a Food and Drug Administration
Investigational Device Exemption that was not the same as the Humanitarian
Device Exemption (HDE) for the stent. This does not make the SAMMPRIS
results "dubious". SAMMPRIS conclusively showed that angioplasty and
stenting for the high risk WASID population was worse than aggressive
medical management. Moreover, a subgroup analysis in patients who had
failed antithrombotic therapy at the time of their qualifying event for
SAMMPRIS (i.e., those patients that met the HDE criteria) also showed that
angioplasty and stenting was worse than aggressive medical management in
these patients (Lutsep, et al., 2012 International Stroke Conference, Los
Angeles, CA).
Finally, there was never a policy that all 20 cases of angioplasty
and stenting submitted for credentialing had to be with the Wingspan
device, as stated by Dr. Alexander. We required documentation of 20
consecutive intracranial angioplasty and/or stenting cases and accepted
experience with similar devices 3. These cases and their outcomes were
carefully reviewed by a credentialing committee composed of experienced
neuro interventionists. The fact that interventionists with the least
experience with Wingspan had similar event rates as those with the highest
experience indicates that this system identified a very capable group of
neurointerventionists (Derdeyn, et al., 2012 International Stroke
Conference, Los Angeles, CA). In at least one of the carotid stenting
trials mentioned by Dr. Alexander, some interventionists were allowed to
participate without the requisite experience as long as they were
proctored during the procedure 4. Others were allowed in with as few as
five total carotid angioplasty and stenting cases (with any device). This
was not permitted in SAMMPRIS.
We agree wholeheartedly that we still have much to learn about this
disease and its treatment.
Sincerely,
References:
1. Kasner SE, Chimowitz MI, Lynn MJ, Howlett-Smith H, Stern BJ,
Hertzberg VS, Frankel MR, Levine SR, Chaturvedi S, Benesch CG, Sila CA,
Jovin TG, Romano JG, Cloft HJ. Predictors of ischemic stroke in the
territory of a symptomatic intracranial arterial stenosis. Circulation.
2006;113:555-563
2. Derdeyn CP. Mechanisms of ischemic stroke secondary to large artery
atherosclerotic disease. Neuroimaging Clin N Am. 2007;17:303-311, vii-viii
3. Chimowitz MI, Lynn MJ, Turan TN, Fiorella D, Lane BF, Janis S, Derdeyn
CP. Design of the stenting and aggressive medical management for
preventing recurrent stroke in intracranial stenosis trial. J Stroke
Cerebrovasc Dis. 2011;20:357-368
4. Mas JL, Chatellier G, Beyssen B, Branchereau A, Moulin T, Becquemin JP,
Larrue V, Lievre M, Leys D, Bonneville JF, Watelet J, Pruvo JP, Albucher
JF, Viguier A, Piquet P, Garnier P, Viader F, Touze E, Giroud M, Hosseini
H, Pillet JC, Favrole P, Neau JP, Ducrocq X. Endarterectomy versus
stenting in patients with symptomatic severe carotid stenosis. N Engl J
Med. 2006;355:1660-1671
I appreciate that case reports are extremely important in
establishing the potential viability of interventions. However, it is an
overstatement to conclude that a single case report demonstrates the
"safety" of the given approach.
What the case report does indicate is that the technique is feasible
and that it can be performed safely in this one case and agreeably merits
fur...
I appreciate that case reports are extremely important in
establishing the potential viability of interventions. However, it is an
overstatement to conclude that a single case report demonstrates the
"safety" of the given approach.
What the case report does indicate is that the technique is feasible
and that it can be performed safely in this one case and agreeably merits
further work to establish the overall safety.
I write to congratulate the authors on a fine basic review of spinal
cord vasculature and related imaging modalities, but also to point out
that as time goes by, the older literature may fall by the wayside,
largely forgotten. Ordinarily I try not to act like a dinosaur and point
such things out, but the authors do mention (on page 69) in reviewing the
vascular supply of the cervical spinal cord, that "according to
"Dji...
I write to congratulate the authors on a fine basic review of spinal
cord vasculature and related imaging modalities, but also to point out
that as time goes by, the older literature may fall by the wayside,
largely forgotten. Ordinarily I try not to act like a dinosaur and point
such things out, but the authors do mention (on page 69) in reviewing the
vascular supply of the cervical spinal cord, that "according to
"Djindjan", other small contributors may arise from the costocervical
trunk....". Not only is the name misspelled (I imagine this could have
been an error in editing at the journal), but Dr. Djindjian is quoted and
yet there is no cited reference to his pioneering work anywhere in the
manuscript. I assume that one of the authors is familiar with his work,
and wanted to credit him in this way and that is commendable.
We who work and have worked on patients with neurovascular disease of
the cord owe much to the work of Rene Djindjian, formerly professor and
chief of the Department of Neuroradiology at l'Hopital Lariboisiere in
Paris. He took the relatively new (at the time) technique of selective
angiography, and applied it to the spinal cord and spinal cord disease.
There are ample opportunities for citations: his countless peer reviewed
papers, as well as his (now sadly long out of print) classic text,
L'Angiographie De La Moelle Epiniere (Angiography of the Spinal Cord),
authored by Djindjian (as well as co-authors including Hurth and Houdart)
with a preface by Guy Lazorthes (formerly Chief of Neurosurgery, and Dean
of the University of Medicine and Pharmacy of Toulouse), translated into
English by Irvin I. Kricheff (New York), and published in 1970 (Masson
& Cie, Paris and University Park Press, Baltimore, 482pp).
I do not mean to say that we must be familiar with everything from
the past that informs our current practice, but it is important to not
forget those who were so critical in advancing the dynamic field that
benefits so many of our patients today. Again, I credit the authors for
remembering this. I write primarily for the sake of those who may read
this paper who may not know of Djindjian's work and may learn from it more
directly. Anyone currently working in the field of Neurointerventional
Surgery should make an effort to find a copy of this text, and learn from
a master.
Dear Sir,
We thank the authors for their letter entitled, "Caution during use of DDAVP in IPSS," by Drs. Pecori Giraldi, Federici, and Cavagnini. The authors suggest that because of the hypercoagulable state that characterizes Cushing disease, DDAVP may not be safe since it has been shown to increase the level of von Willebrand factor (vWF) and could therefore lead to platelet adhesion and cause thromboembolism...
Dear Sir, we have read with great interest the paper by Deipolyi and co-workers on the use of desmopressin during inferior petrosal sinus sampling (IPSS) in alternative to corticotropin-releasing hormone (CRH) for the diagnostic work-up of Cushing's disease (1). As the Authors report, evidence collected in small series suggests that desmopressin achieves an equivalent diagnostic accuracy to CRH, thus appears a tempting...
The reply from Perez et al to my letter of March 2012 is misleading and wrong in two important regards.1 First, they state that their report of the use of the solitaire stent for thrombectomy was just a case report, "nothing else". 2 This is not true. In fact, they explicitly use this report, both in the abstract and conclusion to lay claim for developing the stentreiever concept for thrombectomy: "This was the first...
We would like to add our strong support to the recent editorial by Fiorella, et al. Dr. Fiorella and his colleagues should be congratulated for pointing out the giant elephant in the room. The government, insurers and patients are increasingly demanding more quality, safety and value from the healthcare dollar and, like it or not, we can no longer ignore their pleas. Dr. Fiorella has eloquently shown us with widely ava...
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...
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 isc...
The response from the Stenting and Aggressive Medical Management for the Prevention of Recurrent Ischemic Stroke (SAMMPRIS) trial principal investigators (PIs) is greatly appreciated. Healthy debate helps us weed out the details that are important in these studies and future trial design. Although the PIs label some of the editorial comments as "inaccuracies", one could disagree based on the information listed below....
As the Principal Investigators for the Stenting and Aggressive Medical Management for the Prevention of Recurrent Ischemic Stroke (SAMMPRIS) trial, we are compelled to address a few inaccuracies regarding this study in the recent editorial by Dr. Alexander.
The first point is the patient population. The SAMMPRIS population was the right patient population to test. We had very good data from the Warfarin vers...
Dear Author & Editor
I appreciate that case reports are extremely important in establishing the potential viability of interventions. However, it is an overstatement to conclude that a single case report demonstrates the "safety" of the given approach.
What the case report does indicate is that the technique is feasible and that it can be performed safely in this one case and agreeably merits fur...
I write to congratulate the authors on a fine basic review of spinal cord vasculature and related imaging modalities, but also to point out that as time goes by, the older literature may fall by the wayside, largely forgotten. Ordinarily I try not to act like a dinosaur and point such things out, but the authors do mention (on page 69) in reviewing the vascular supply of the cervical spinal cord, that "according to "Dji...
Pages