Thrombolysis Before Thrombectomy for Acute Ischemic Stroke

 93-year-old female with past medical history of hypertension, hyperlipidemia, Mohs surgery 2 weeks ago who was noted to have dyspnea on exertion starting 4/16 after the surgery.  Patient was found to have an EKG showing heart rate of 50 junctional rhythm nonspecific ST and T wave abnormalities, BNP 3800.  Patient was scheduled for pacemaker that was continuously delayed because she required high flow oxygen and a CT scan showing groundglass opacities in the upper lungs likely infectious versus inflammatory.  Patient was treated with diuretics including Lasix and acetazolamide.  Was about to be optimized for pacemaker/24 however stroke code was called for right-sided weakness with NIHSS stroke scale of 24.  Imaging showed left cervical internal carotid artery occlusion as well as circle of Willis collateralization a 2 mm left horizontal middle cerebral artery bifurcation embolus.  Patient was given TNK at 2306.  Patient to be transferred to Mount Sinai for further potential procedures.

93 yo F w HTN, HLP, and symptomatic bradycardia pending PPM with acute onset right hemiplegia and right facial droop. LKN 19:30. Stroke team activated 21:29. NIHSS 24. CTH, CTA head/neck (completed 22:15) notable for L cervical ICA occlusion (possible dissection), with circle of Willis collateralization and acute embolic 2mm occlusion of L MCA. TNK given 23:06. Patient transfered to MSH for possible thrombectomy. Hemodynamically stable and protecting airway throughout RRT. 

Should we skip thrombolysis and go straight for thrombectomy?

Is going straight for thrombectomy noninferior to both thrombolysis and thrombectomy?

2 good studies: 

1- SKIP randomized clinical trial by Suzuki et al in Japan (negative trial for noninferiority)

2- DEVT RCT Wengjie Zi et al in China (positive trial for noninferiority)

Intravenous thrombolysis before endovascular thrombectomy for acute ischemic stroke by China

Interesting Point: In acute myocardial infarction we have skipped straight to the mechanical approach (Catheterization).  However in strokes we still consider thrombolysis/fibrinolytics (Alteplase / TNK) before catheterization (thrombectomy / Endovascular repair).

Key Assumptions: Fibrinolytics including alteplase worked best with small and medium clots that are distal, they do not work well for large proximal clots.

Thrombectomy is good for large proximal clots.

Clots are scary because they can shoot up and occlude smaller arteries.

Let's think about this intuitively first without data:

Why might alteplase may be bad?

- Clots may break upwards: For big clots that can cause increases in bleeding rates and caused clots to fragment upwards and may make patients worse.

- Delay in care: Getting consent from patients delays time to thrombectomy

Why might alteplase may be good?

- reduced clot burden: Alteplase may reduce the clot burden via fibrinolysis and open up the artery before the catheterization lab reducing brain ischemia 

- Alteplase may make the clot more responsive

Okay now let's get into the trials

SKIP RCT by Suzuki et. al

JAMA. 2021;325(3):244-253. doi:10.1001/jama.2020.23522

Question MT alone or MT + IV Thrombolysis?
Dosage 0.6mg / kg of alteplase (In US 0.9 mg/kg)
Characeteristics of population: 41 / 101 were ICA, 19 / 101 were M1 Proximal and 41 / 101 were M1 distal
Outcome: SKIP Trial showed noninferiority in terms of Rankin Scores 0 to 2 days at 90 days

MT alone (59.4%) return of function which is a 2.1% difference versus MT + IV (57.3%). 

Did not meet threshold for noninferiority

Therefore we still don't know if it is better to SKIP!?!? 🤷🤷🤷🤷

DEVT trial Wengjie Zi

JAMA. 2021;325(3):234-243. doi:10.1001/jama.2020.23523

Outcome: Functional independence at 90 days

Groups: EVT alone verse EVT + IV alteplase (0.9 mg/kg) 10% bolus + infusion

Result: Noninferiority was achieved!!!!

"outcome fro thrombectomy alone was noninferior to combined treatment pvalue 0.003"

Interesting differences between the two trials:

- DEVT higher dose of alteplase (0.9 mg/kg), higher time between alteplase and arterial puncture (40 minutes)

- SKIP TPA trial (0.6mg/kg), lower time between alteplase and arterial puncture (8 minutes)

DEVT trial if you give substantial dose of alteplase well ahead of time, will it make a big difference - answer NOT REALLY.

SKIP trial if you give safer lower dose prior to thrombectomy does it help improve outcomes? NOT REALLY

For the young generation, medical lingo cool kids use:

Should we drip and ship?

If you can get to clot, it is not unreasonable to skip thrombolytic therapy

Still at least three more trials looking at this question.

More to come