The correct answer is:

Skipping thrombolysis prior to thrombectomy is not beneficial in terms of functional outcome and the potential for harm cannot be excluded

Educational Objective:

Discuss recent study findings with regards to omitting thrombolysis in patients with large anterior strokes who will undergo expeditious thrombectomy.

Key Point:

When compared to the current standard of care (thrombolysis PLUS thrombectomy), the MR CLEAN study found that skipping thrombolysis prior to even an expeditiously available thrombectomy was neither superior (skipping thrombolysis did not improve functional outcome) nor non-inferior (skipping thrombolysis could not be proven to be harmless).

Explanation:

For patients with anterior circulation strokes who qualify for both thrombolysis and thrombectomy, the current standard of care is to proceed with both procedures in most cases.

This is a similar situation to the early times of percutaneous coronary intervention (PCI), where proceeding with both thrombolysis and PCI was the original standard of care, prior to enough data being available to recommend otherwise.

Subsequent studies in patients with acute myocardial infarction led to the insight that combining both procedures was not beneficial, which led to dual revascularization interventions NO LONGER being recommended in this group (with a few exceptions).

Given this evolution of care in patients with acute myocardial infarction, the question arose if dual revascularization therapy is similarly superfluous in patients with acute stroke.

Four recent studies specifically explored the feasibility of dropping thrombolysis if a patient with an acute anterior stroke qualified for and had access to emergent thrombectomy. Three of these studies were completed in Asian populations, who have somewhat different patterns/incidences of cerebral vascular stenoses than other populations. The fourth study was performed in a mixed population. These studies found:

Superiority of Thrombectomy Alone:

The MR CLEAN study (the only study to test for superiority) found that performing thrombectomy alone (experimental approach) did NOT result in superior outcomes on any outcome measure, as compared to performing thrombolysis followed by thrombectomy (standard of care) 

Non-Inferiority of Thrombectomy Alone:

The MR CLEAN study found that thrombectomy alone (experimental approach) was NOT non-inferior to performing both interventions (standard of care). This (brain-twisting) “not non-inferior” means that the possibility of harm could not be ruled out (presence of harm, on the other hand, was also not established). 

One of the three Asian studies also found that non-inferiority could not be established (possibility of harm could not be excluded), whereas the other two Asian studies found that non-inferiority was present (absence of harm was demonstrated).

Bottom Line:

An editorial discussion (see Ciccone) of all 4 studies concludes that, different from patients with acute myocardial infarction, patients with acute anterior cerebral circulation stroke should continue to receive thrombolysis PLUS thrombectomy when eligible for both interventions. 

Details of MR CLEAN Study:

• On average, patients in the standard of care group received alteplase within 98 minutes of stroke onset (with door-to-needle time of 31 minutes). 
• On average, groin puncture was achieved within 130 minutes of stroke onset (with door-to groin puncture time of 63 minutes) in the experimental group and 135 minutes in the standard of care group (with door-to groin puncture time of 64 minutes). 
• Average rates of functional recovery were slightly less favorable (average modified Rankin = 3) in the experimental group versus the standard of care group (average modified Rankin = 2). This difference exceeded the study’s odds ratio shift allowed for non-inferiority (meaning that within the power of this study, the absence of harm caused by the experimental approach could not be proven). 
• Rates of symptomatic hemorrhage differed to a statistically non-significant degree (5.3% in experimental group versus 5.9% in standard of care group). Rates of any bleeding were 35% in both groups.
• In the study group (no thrombolysis prior to thrombectomy), 7.3% of patients required rescue thrombolysis after thrombectomy. 
• The study did not break down the results according to time intervals (e.g., 60-minute answer is false).
• Patients requiring inter-hospital transport were excluded from the study.

References:

LeCouffe NF, Kappelhof M, Treurniet KM, et al. A Randomized Trial of Intravenous Alteplase before Endovascular Treatment for Stroke. New Engl J Med 2021; 385:1833-1844. DOI: 10.1056/NEJMoa2107727

Ciccone A. Alteplase and Thrombectomy - Not a Bridge to Dismantle. Editorial. N Engl J Med 2021; 385:1904-1905. Nov 11, 2021 DOI: 10.1056/NEJMe2112663

Suzuki K, Matsumaru Y, Takeuchi M, et al. Effect of mechanical thrombectomy without vs with intravenous thrombolysis on functional outcome among patients with acute ischemic stroke: the SKIP randomized clinical trial. JAMA 2021; 325:244-253.

Si W, QIU Z, Li F, et al. Effect of endovascular treatment alone vs intravenous alteplase plus endovascular treatment of functional independence in patients with acute ischemic stroke: the DEVT randomized clinical trial. JAMA 2021; 325:234-243.