Updated in Treatment of Acute Ischemic Stroke: Intravenous r-TPA or Endovascular Therapy

Updated in Treatment of Acute Ischemic Stroke: 
Intravenous r-tPA or Endovascular Therapy 
Nguyen Quang Anh, MD 
VIETNAM NATIONAL CONGRESS OF CARDIOLOGY 
15th Meeting, Ninh Binh 
Introduction 
• Ischemic: 80% of stroke 
• Third leading cause of dead in developed country 
• Cardiovascular disease, diabetes, 
• 2025: prediction of 1.2 millions patients/year 
• In Viet Nam, stroke is top cause of Death (account 
for 18% - 2008) 
“Time is brain”! 
Protocol in BM Hospital from 2012-15 
Administered to the Emergency Department (10 mins) 
First aid with clinical examination and test (35 mins) 
CT/MRI (non contrast, angio, multiphase/ perfusion) (15-25mins) 
Hemorrhage 
Rule out 
Ischemic with evidence of 
big arteries occlusion 
IR room (60 mins) 
Treatment 
• IV r-tPA (NINDS) 
 -> approved by FDA 1995 
• Time window: 
• 3h (NINDS)/ <1% ischemic stroke patients received treatment * 
• 4.5h (ECASS III) ** 
• Number need to treat (NNT): 
 1/5 (90’) -> 1/9 (180’) -> 1/14 (4.5h) 
• > 4.5h: more harmful than benefit 
• New: Demoteplase (DIAS III), Tenecteplase 
(*) Group, NINDS rt-PA Stroke Study, (1995). N Engl J Med. 333(24): p. 1581-7. 
(**) Hacke, Werner, et al., (2008). New England Journal of Medicine. 359(13): p. 1317-1329. 
– IV only should be done in first 4.5 hours (the shorter 
time, the better result) 
• NOT GOOD with proximal part of main arteries 
(10% ICA, 30% M1 in revascularization) * 
(*) Group, NINDS rt-PA Stroke Study, (1995). N Engl J Med. 333(24): p. 1581-7. 
Indication 
– Age ≥ 18 
– Clinical diagnosis of ischemic stroke causing 
neurological deficit 
– Time of onset symptoms ≤ 4.5 hours 
– Non-contrast CT scan showing no hemorrhage or 
well-establish new infarct 
Contraindication 
– Large infarction in CT Scanner 
– History of intracranial hemorrhage or brain aneurysm or 
vascular malformation or brain tumor 
– Suspicion of SAH 
– SBP ≥ 185mmHg or DBP ≤ 110mmHg 
– Seizure at onset 
– Recent surgery/trauma (less than 15 days) 
– Recent intracranial or spinal surgery, head trauma, or stroke 
(less than 3 months) 
– Active internal bleeding (less than 22 days) 
– Platelets ≤ 100.000 or INR > 1.5 
– ... 
Recommendation from AHA/ASA 
guidelines 2015 
– Patients eligible for intravenous r-tPA should receive 
r-tPA even if endovascular treatments are being 
consider (Class 1; Level of Evidence A) 
– In careful selected patients with anterior circulation 
occlusion who have contraindications to intravenous 
r-tPA, endovascular therapy with stent retrievers 
completed within 6 hours of stroke onset is reasonable 
(Class 2a, Level of Evidence C) 
Endovascular Therapy 
• «Bridging Therapy»: Intravenous r-tPA + Mechanical 
Thrombectomy – waiting for 45mins – 1 hour 
• Intra-arterial r-tPA: 
– Not effective compared to mechanical thrombectomy 
– Increase hemorrhage rate post-treatment 
• Mechanical Thrombectomy 
Penumbra 
2006 
Pump-Canister
Tubing
Sterile
Aspiration
Tubing
RHV to
Reperfusion
Catheter on/off switch
Revive 
Trevo 
Merci 
2004 
Devices 
Solitaire 
2010 
Advantages: 
– Faster revascularization 
– Good for big vessels 
– Extend time window to 6-8h 
– Less symptomatic intracranial 
hemorrhage 
– Who have contraindication 
with thrombolysis 
Disadvantages: 
• High cost (3-4000 USD) 
• Shatter & mirage small 
thrombus to small vessel 
• Damage to vessels wall 
 RESULTS IS GOOD 
BUT 
IMS III 
SYNTHESIS 
MR Rescue 
MR RESCUE 
• All 3 (and other recent) trials showed that 
endovascular therapy is NOT SUPERIOR 
when compared to IV rt-PA 
WHY? 
IV trials weakness 
• Inclusion of patients with slight clinical deficiency by 
very low NIHSS 
• Involved small arteries occlusion 
• Old devices 
• Late time window for Mechanical Thrombectomy 
IMS III Design 
IV rt-PA initiated within 3 hours 
NIHSS ≥ 10 (or 8-9 with ICA, M1, BA 
occlusion on CTA) 
Randomized within 40 min of IV rt-PA start 
Adjunctive endovascular Therapy 
Start by 5 hours, max duration of 2 hours, 
completed by 7 hours 
IV rt-PA alone 
IA rt-PA 
Via standard 
microcatheter 
IA rt-PA 
Via EKOS 
Ultrasound 
catheter 
MERCI 
Retriever 
Penumbra 
Aspiration 
Solitaire 
Stent Retriever 
Results 
• Technique 
– 37.8% (164/434) IA rt-PA 
– 34.3% (149/434) MT with old devices (Merci or 
Penumbra) 
– Only 1.2% (5/434) MT with new devices (stent 
retrievers) 
-> 5 Stent Retriever used in this study!!! 
Recently Evidences 
• IMS III, SYNTHESIS, MR RESCUE, EXTEND-IA 
• SWIFT PRIME, REVASCAT 
• MR CLEAN 
• ESCAPE 
MR CLEAN 
Design and results 
• Methods 
– IV >< IV + MT in the first 4.5 hours 
– Treatment up to 6 hours with anterior circulation occlusion 
• Results 
– 267 >< 233 (190/233-81.5% treated with stent retriever) 
– 445/500-89% treated with IV-tPA 
– mRS 0-2: 19.1% > Thrombectomy is better 
– Symptomatic hemorrhage: no significant difference 
ESCAPE 
Design and results 
• Methods 
– IV >< IV + MT in the first 4.5 hours 
– 238/316 received rt-PA with 118 control >< 120 intervention 
– Treatment up to 12 hours with anterior circulation occlusion 
– NO large infarct core (ASPECTs < 6), NO poor collateral (<50% 
filling pial artery of the MCA in the CT Multiphase) 
• Results 
– Stop early because of the efficacy 
– Times from CT non contrast to groin puncture: 60mins/ to first 
reperfusion: < 90 mins 
– mRS 0-2: 29.3% > Thrombectomy is better 
– Mortality: 19% >< 10.4% 
– Symptomatic hemorrhage: 2.7% >< 3.6% 
Conclusion from guidelines 2015 
– Based on 8 randomized clinical trials 2013-2015 
– “Certain endovascular procedures have been 
demonstrated to provide clinical benefit in selected 
patients with acute ischemic stroke” 
Protocol changes 
• 1) Treatment: 
– IV + MT in the first 4.5 hours 
– After 4.5 hours, mechanical thrombectomy only 
– No later than 6 hours 
• 2) Good patients selection: 
– NIHSS: from 6 (to 25) 
– Age ≥ 18 (to 80) 
– ASPECTS ≥ 6 
• 3) Big arterial Occlusion (M1, ICA)/ Good collateral 
Solitaire 
(Priority) 
+ 
Good combination 
IV r-tpA 
(For < 4.5hrs but don’t wait, do the 
Mechanical Thrombectomy 
 right after transfusion) 
Conclusion 
• Acute ischemic stroke is still the challenge, 
always keep up to date 
• Treatment: do not wait, try the combination IV-
tPA with Mechanical Thrombectomy in the first 
4.5 hours window if possible 
Case 
• Male patient, 53 years old 
• Normal history 
• Suddenly right hemiplegia 
• Administered to hospital within 2nd hours 
• NIHSS = 16 
MRI 
TICI = 3 
mRS = 1 
Before 
After 
THANK YOU FOR YOUR ATTENTION