1. Erik Oltmann, PGY-1 August 20, 2015
LSU Journal Club
“Stent-Retriever Thrombectomy after Intravenous t-PA vs t-PA Alone in Stroke” NEJM June 11, 2015; 372: ; DOI: /NEJMoa SWIFT PRIME Investigators, et al.
Erik Oltmann, PGY-1
August 20, 2015

2. Background 795,000 patients experience an Ischemic Stroke each year
t-PA only effective when given within 4.5 hours of onset
Effective in <30% of patients with a Large Occlusion of Major Vessels (13-50% in M1 of MCA and Intracranial ICA)
Stent-Retrieval devices Entrap the Thrombus between the stent and the vessel wall to restore Anterograde Blood Flow
Struts on the stent allows thrombotic material to be Retrieved by the Catheter
tPA at 4.5 hours:
- Age <80 | NO DM2 + stroke | NO Coumadin/warfarin | NIHSS <25

3. Research Question
Is the addition of Stent-Retriever Thrombectomy to IV t-PA for Acute Ischemic Stroke involving the Proximal Anterior Intracranial Circulation a Safe and Efficacious treatment?
establish the efficacy and safety of rapid neurovascular thrombectomy with the stent retriever in conjunction with intravenous t-PA versus intravenous t-PA alone in patients with acute ischemic stroke.

4. Study Design
December 2012 through November 2014, 196 patients enrolled in SWIFT PRIME Trial
Solitaire with the Intention for Thrombectomy as Primary Endovascular Treatment
International, Multicenter, Prospective, Randomized, Clinical Trial
39 centers in the US and Europe

5. Study Design: INCLUSION CRITERIA
Years of Age
Acute Ischemic Stroke with a NIHSS Score of (Mod-Sev deficit) and Baseline Modified Rankin Score <1
Imaging-confirmed occlusion of the Intracranial Internal Carotid Artery, the First Segment of Middle Cerebral Artery, or Both
Receiving or had received IV t-PA within 4.5 hrs, and able to undergo initiation of Endovascular Treatment within 6 hrs of Onset
Modified Rankin: 0-6
1 = no significant disability
2 = slight; able to perform ADLs
3 = mod; able to walk unassisted; some help
4 = mod-sev; unable to walk w/o assist; unable to independent perform ADLs
5 = sev; bedridden, incontinent
6 = death

6. Study Design: EXCLUSION CRITERIA
t-PA Contraindicated
Rapid Improvement of Neuro Symptoms
Contrast and Metal Allergies
Hereditary or Acquired Bleeding Diathesis
Creatinine >2.0 | GFR <30 | ESRD on Dialysis
Presentation suggestive of Aortic Dissection or SAH
Comorbidities that would confound Neuro and Functional Evaluation
Contraindications for t-PA: evidence of hemorrhage on CT; clinical suspicion of SAH; multi-lobar ischemia; hx of hemorrhage; BP >185/>110; PLT <100,000; Heparin w/i 48 or current Hep/Warf use; elevated PTT
Relative Contraindications: NIHSS>22 or<4 or rapidly improving; 14d post op or post trauma; recent GI/GU hemorrhage (21d); recent AMI (3 mos); pericarditis;
Glucose<50 OR >400; Age>80; hx of ischemic stroke AND diabetes
These questions help you to identify if the study is valid (internal validity) and whether the results are generalizable to the sort of patients you are likely to see. (external validity)

7. Study Design Patients balanced with respect to 4 factors:
Investigational Site
Baseline Severity: NIHSS score ≤17 vs. >17
Age: <70 yoa vs. ≥70 yoa
Occlusion Location: Middle Cerebral vs. Internal Carotid
Randomly assigned to one of two treatment groups:
Intervention Group (98): IV t-PA plus Stent Retriever
Control Group (98): IV t-PA alone
Patients Evaluated at 27 hrs  7-10 days  30 days  90 days
**10 patients in interventional group lost to follow up or did not receive thrombectomy

8. Demographic and Clinical Characteristics
Saver JL et al. N Engl J Med 2015;372:

9. Demographic and Clinical Characteristics
Saver JL et al. N Engl J Med 2015;372:

10. Results
INTERVENTION GROUP: median time from onset to groin puncture was 224 min
88% of patients regained Substantial Reperfusion
Reduced disability at 90 days over the Entire Range of scores on the Modified Rankin scale (P<0.001)
The rate of functional independence (mRS score 0 to 2) was higher in Intervention group than Control group
60% vs. 35%, P<0.001
NO Significant Differences between groups in 90-day Mortality (9% vs. 12%, P = 0.50) or Symptomatic Intracranial Hemorrhage (0% vs. 3%, P = 0.12)
Less Disabled: NNT = 2.6
Functionally Independent: NNT = 4 | RR = 1.7

11. Saver JL et al. N Engl J Med 2015;372:2285-2295.
Primary and Secondary Outcomes
Saver JL et al. N Engl J Med 2015;372:
Figure 2. Analysis of Functional Independence at 90 Days in Pre-specified Subgroups. 
Functional independence was defined as a score on the modified Rankin scale of 0, 1, or 2. P values were based on the Breslow–Day test for homogeneous odds ratios across subgroups. Squares indicate point estimates for treatment effects, and the size of the square is proportional to the precision of the estimate. Scores on the National Institutes of Health Stroke Scale (NIHSS) range from 0 to 42, with higher scores indicating more severe neurologic deficits. The threshold of 17 was the threshold used in stratifying randomization. The Alberta Stroke Program Early CT Score (ASPECTS) ranges from 0 to 10, with higher scores indicating a smaller infarct core; a score of 6 or 7 indicates moderate infarct core, and a score of 8 or higher small infarct core. For the time from stroke onset to randomization, the median value was prespecified as the cutoff point for analysis and was found to be 189 minutes. M1 denotes first segment of the middle cerebral artery, and M2 second segment of middle cerebral artery.

12. Saver JL et al. N Engl J Med 2015;372:2285-2295.
Primary and Secondary Outcomes
Saver JL et al. N Engl J Med 2015;372:
Figure 2. Analysis of Functional Independence at 90 Days in Pre-specified Subgroups. 
Functional independence was defined as a score on the modified Rankin scale of 0, 1, or 2. P values were based on the Breslow–Day test for homogeneous odds ratios across subgroups. Squares indicate point estimates for treatment effects, and the size of the square is proportional to the precision of the estimate. Scores on the National Institutes of Health Stroke Scale (NIHSS) range from 0 to 42, with higher scores indicating more severe neurologic deficits. The threshold of 17 was the threshold used in stratifying randomization. The Alberta Stroke Program Early CT Score (ASPECTS) ranges from 0 to 10, with higher scores indicating a smaller infarct core; a score of 6 or 7 indicates moderate infarct core, and a score of 8 or higher small infarct core. For the time from stroke onset to randomization, the median value was prespecified as the cutoff point for analysis and was found to be 189 minutes.

13. Saver JL et al. N Engl J Med 2015;372:2285-2295.
Functional Independence at 90 Days
Saver JL et al. N Engl J Med 2015;372:
Figure 2. Analysis of Functional Independence at 90 Days in Pre-specified Subgroups. 
Functional independence was defined as a score on the modified Rankin scale of 0, 1, or 2. P values were based on the Breslow–Day test for homogeneous odds ratios across subgroups. Squares indicate point estimates for treatment effects, and the size of the square is proportional to the precision of the estimate. Scores on the National Institutes of Health Stroke Scale (NIHSS) range from 0 to 42, with higher scores indicating more severe neurologic deficits. The threshold of 17 was the threshold used in stratifying randomization. The Alberta Stroke Program Early CT Score (ASPECTS) ranges from 0 to 10, with higher scores indicating a smaller infarct core; a score of 6 or 7 indicates moderate infarct core, and a score of 8 or higher small infarct core. For the time from stroke onset to randomization, the median value was prespecified as the cutoff point for analysis and was found to be 189 minutes. M1 denotes first segment of the middle cerebral artery, and M2 second segment of middle cerebral artery.

14. Saver JL et al. N Engl J Med 2015;372:2285-2295.
Functional Independence at 90 Days
Saver JL et al. N Engl J Med 2015;372:
ASPECTS Scores
Figure 2. Analysis of Functional Independence at 90 Days in Pre-specified Subgroups. 
Functional independence was defined as a score on the modified Rankin scale of 0, 1, or 2. P values were based on the Breslow–Day test for homogeneous odds ratios across subgroups. Squares indicate point estimates for treatment effects, and the size of the square is proportional to the precision of the estimate. Scores on the National Institutes of Health Stroke Scale (NIHSS) range from 0 to 42, with higher scores indicating more severe neurologic deficits. The threshold of 17 was the threshold used in stratifying randomization. The Alberta Stroke Program Early CT Score (ASPECTS) ranges from 0 to 10, with higher scores indicating a smaller infarct core; a score of 6 or 7 indicates moderate infarct core, and a score of 8 or higher small infarct core. For the time from stroke onset to randomization, the median value was prespecified as the cutoff point for analysis and was found to be 189 minutes. M1 denotes first segment of the middle cerebral artery, and M2 second segment of middle cerebral artery.

15. Saver JL et al. N Engl J Med 2015;372:2285-2295.
Functional Independence at 90 Days
Saver JL et al. N Engl J Med 2015;372:

16. Safety Outcomes

17. Safety Outcomes

18. Safety Outcomes

19. Conclusions Improved 90 day Functional independence
Modified Rankin Score <2
Better outcomes across ALL scores of Rankin
More successful reperfusion at 27hrs
83% vs 40%
No significant difference in rates of ALL intracranial hemorrhage
Numerically more SAH with Thrombectomy
These questions help you to identify if the study is valid (internal validity) and whether the results are generalizable to the sort of patients you are likely to see. (external validity)

20. Limitations Small, Homogenous patient population
Need to expand the demographics
Only studied in the M1 Segment of MCA and Intracranial ICA
Further studies in more Distal Vessels
Sites were Tertiary Care Centers with established Stroke-Intervention programs and skilled Interventionalists
Safety in Non-tertiary Centers?
No significant difference in relative benefit on pts sent on transfer from OSH

21. Authors
Jeffrey L. Saver, M.D., Mayank Goyal, M.D., Alain Bonafe, M.D., Hans-Christoph Diener, M.D., Ph.D., Elad I. Levy, M.D., Vitor M. Pereira, M.D., Gregory W. Albers, M.D., Christophe Cognard, M.D., David J. Cohen, M.D., Werner Hacke, M.D., Ph.D., Olav Jansen, M.D., Ph.D., Tudor G. Jovin, M.D., Heinrich P. Mattle, M.D., Raul G. Nogueira, M.D., Adnan H. Siddiqui, M.D., Ph.D., Dileep R. Yavagal, M.D., Blaise W. Baxter, M.D., Thomas G. Devlin, M.D., Ph.D., Demetrius K. Lopes, M.D., Vivek K. Reddy, M.D., Richard du Mesnil de Rochemont, M.D., Oliver C. Singer, M.D., and Reza Jahan, M.D., for the SWIFT PRIME Investigators*

22. References http://www.medscape.com/viewarticle/772506_3