MR Rescue NEJM 2013

Background
Whether brain imaging can identify patients who are most likely to benefit from
therapies for acute ischemic stroke and whether endovascular thrombectomy improves
clinical outcomes in such patients remains unclear.
Methods
In this study, we randomly assigned patients within 8 hours after the onset of largevessel,
anterior-circulation strokes to undergo mechanical embolectomy (Merci
Retriever or Penumbra System) or receive standard care. All patients underwent
pretreatment computed tomography or magnetic resonance imaging of the brain.
Randomization was stratified according to whether the patient had a favorable
penumbral pattern (substantial salvageable tissue and small infarct core) or a nonpenumbral
pattern (large core or small or absent penumbra). We assessed outcomes
using the 90-day modified Rankin scale, ranging from 0 (no symptoms) to 6 (dead).
Results
Among 118 eligible patients, the mean age was 65.5 years, the mean time to enrollment
was 5.5 hours, and 58% had a favorable penumbral pattern. Revascularization
in the embolectomy group was achieved in 67% of the patients. Ninety-day mortality
was 21%, and the rate of symptomatic intracranial hemorrhage was 4%; neither rate
differed across groups. Among all patients, mean scores on the modified Rankin
scale did not differ between embolectomy and standard care (3.9 vs. 3.9, P = 0.99).
Embolectomy was not superior to standard care in patients with either a favorable
penumbral pattern (mean score, 3.9 vs. 3.4; P = 0.23) or a nonpenumbral pattern
(mean score, 4.0 vs. 4.4; P = 0.32). In the primary analysis of scores on the 90-day
modified Rankin scale, there was no interaction between the pretreatment imaging
pattern and treatment assignment (P = 0.14).
Conclusions
A favorable penumbral pattern on neuroimaging did not identify patients who would
differentially benefit from endovascular therapy for acute ischemic stroke, nor was
embolectomy shown to be superior to standard care. (Funded by the National Institute
of Neurological Disorders

 

Blogger comment:  key point here is mean time to vascularization has to be less than 8 hours.  MR rescue should be done within six or preferably four hours.

IMS 3 article

Endovascular Therapy after Intravenous
t-PA versus t-PA Alone for Stroke
Joseph P. Broderick, M.D., Yuko Y. Palesch, Ph.D., Andrew M. Demchuk, M.D., et al NEJM 2013

 

BACKGROUND
Endovascular therapy is increasingly used after the administration of intravenous tissue
plasminogen activator (t-PA) for patients with moderate-to-severe acute ischemic
stroke, but whether a combined approach is more effective than intravenous t-PA
alone is uncertain.
METHODS
We randomly assigned eligible patients who had received intravenous t-PA within
3 hours after symptom onset to receive additional endovascular therapy or intravenous
t-PA alone, in a 2:1 ratio. The primary outcome measure was a modified
Rankin scale score of 2 or less (indicating functional independence) at 90 days
(scores range from 0 to 6, with higher scores indicating greater disability).
RESULTS
The study was stopped early because of futility after 656 participants had undergone
randomization (434 patients to endovascular therapy and 222 to intravenous t-PA
alone). The proportion of participants with a modified Rankin score of 2 or less at
90 days did not differ significantly according to treatment (40.8% with endovascular
therapy and 38.7% with intravenous t-PA; absolute adjusted difference, 1.5 percentage
points; 95% confidence interval [CI], −6.1 to 9.1, with adjustment for the National
Institutes of Health Stroke Scale [NIHSS] score [8–19, indicating moderately severe
stroke, or ≥20, indicating severe stroke]), nor were there significant differences for
the predefined subgroups of patients with an NIHSS score of 20 or higher (6.8
percentage points; 95% CI, −4.4 to 18.1) and those with a score of 19 or lower (−1.0
percentage point; 95% CI, −10.8 to 8.8). Findings in the endovascular-therapy and
intravenous t-PA groups were similar for mortality at 90 days (19.1% and 21.6%, respectively;
P = 0.52) and the proportion of patients with symptomatic intracerebral hemorrhage
within 30 hours after initiation of t-PA (6.2% and 5.9%, respectively; P = 0.83).
CONCLUSIONS
The trial showed similar safety outcomes and no significant difference in functional
independence with endovascular therapy after intravenous t-PA, as compared with
intravenous t-PA alone. (Funded by the National Institutes of Health and others;
ClinicalTrials.gov number, NCT00359424.)

 

Blogger comment

 

There's a lot of issues with the studies:

IMS III:

1) IMS III only included patients that arrived in <3 hours and could get IV tPA.

2) Patients that are not candidates for IV tPA (recent surgery, coumadin, etc) undergo endovascular mechanical thrombectomy.

3) 5197 patients were screened for IMS III, but only 656 patients randomized, which typically means the confined scope of a PRCT does not generalize to the real world.

4) For most of IMS III, noncontrast CT was the only imaging (CTA was only added later) which means there were likely a significant number of patients withOUT an occlusion that were randomized in the study (in the Ciccone study, 10% of patients did not have an occlusion!).

5) IMS III included a hodge-podge of endovascular treatments including EKOS, which no one uses, and IA tPA, which is rarely used now that we have mechanical thrombectomy devices.

6) The study was halted because of futility, thus the number of patients studied was not enough for the study to be adequately powered to demonstrate a difference.

7) IMS III was a comparison of IV tPA versus IV tPA plus endovascular therapy. What the study shows is maybe IV tPA is our best treatment. However, the way we practice, and most high-volume stroke centers are the same, is we give IV tPA to eligible candidates and only perform endovascular therapy in patients that are not eligible for IV tPA, or who receive IV tPA and the IV tPA does not work.

8)  Current devices in past year are much more effective and current protocols stress earlier door to needle.

Synthesis trial

SYNTHESIS N Engl J Med 2013

Background
In patients with ischemic stroke, endovascular treatment results in a higher rate of
recanalization of the affected cerebral artery than systemic intravenous thrombolytic
therapy. However, comparison of the clinical efficacy of the two approaches is
needed.
Methods
We randomly assigned 362 patients with acute ischemic stroke, within 4.5 hours
after onset, to endovascular therapy (intraarterial thrombolysis with recombinant
tissue plasminogen activator [t-PA], mechanical clot disruption or retrieval, or a
combination of these approaches) or intravenous t-PA. Treatments were to be given
as soon as possible after randomization. The primary outcome was survival free of
disability (defined as a modified Rankin score of 0 or 1 on a scale of 0 to 6, with
0 indicating no symptoms, 1 no clinically significant disability despite symptoms,
and 6 death) at 3 months.
Results
A total of 181 patients were assigned to receive endovascular therapy, and 181 intravenous
t-PA. The median time from stroke onset to the start of treatment was
3.75 hours for endovascular therapy and 2.75 hours for intravenous t-PA (P<0.001).
At 3 months, 55 patients in the endovascular-therapy group (30.4%) and 63 in the
intravenous t-PA group (34.8%) were alive without disability (odds ratio adjusted for
age, sex, stroke severity, and atrial fibrillation status at baseline, 0.71; 95% confidence
interval, 0.44 to 1.14; P = 0.16). Fatal or nonfatal symptomatic intracranial
hemorrhage within 7 days occurred in 6% of the patients in each group, and there
were no significant differences between groups in the rates of other serious adverse
events or the case fatality rate.
Conclusions
The results of this trial in patients with acute ischemic stroke indicate that endovascular
therapy is not superior to standard treatment with intravenous t-PA. (Funded
by the Italian Medicines Agency, ClinicalTrials.gov number, NCT00640367.)

 

Blogger comment-- endovascular v tpa does not represent real world since current protocol is patients get iv if eligible and both if iv does not work,and endovascular alone if not eligible for iv. Also hodgepodge of old interventional methods were used.

SYNTHESIS (Italian Study):

1) This study only randomized patients that arrived in < 4.5 hours and were eligible candidates for IV tPA. For same reasons as above, this is a very narrow scope of patients.

2) This study was a comparison of IV tPA versus IA tPA (additional devices could be used). IA tPA is rarely used as an endovascular therapy now that we have mechanical devices.

3) No CTA was allowed in this study. Only noncontrast head CT. 10% of patients randomized to IA therapy had no occlusion on angiogram, and these patients because the protocol dictated, were given IA tPA anyways even if they had no occlusion!

4) In his presentation, Ciccone showed that the time-to-treatment was significantly different: >60 minutes longer in the IA treatment arm of the study.

5) It is not clear how many patients were screened to arrive at the final enrollment of 362.