Kevin S. Attenhofer, MD

Ferrigno M, Bricout N, Leys D, Estrade L, Cordonnier C, Personnic T, et al. Intravenous Recombinant Tissue-Type Plasminogen Activator: Influence on Outcome in Anterior Circulation Ischemic Stroke Treated by Mechanical Thrombectomy. Stroke. 2018

2015 was a big year for stroke. For the first time in 20 years, stroke practitioners demonstrated an effective tool in the treatment of acute ischemic stroke. Mechanical thrombectomy (MT) quickly became standard practice. While MT was proposed as an adjunctive therapy for stroke in addition to IV-rtPA (IVT), many of the 2015 trials, as well as the subsequent imaging based trials (DAWN, DEFUSE 3), included patients who did not receive IVT.

The benefit of MT was similar in patients who received IVT and MT compared to MT alone in some trials. This has led some to suggest that MT alone could be a treatment option which maximizes potential benefit while minimizing some of the risks associated with IVT (such as hemorrhage). In fact, I’ve seen non-neurology physicians advocate for MT to replace IVT entirely. Still, others argue that IVT facilitates MT (higher rate of successful recanalization, shorter procedures, and shorter time to recanalization) as well as dissolving distal clots. To date, no randomized controlled trial has compared combination IVT/MT versus MT alone. A recent meta-analysis of the 2015 thrombectomy trials seems to support the latter view: that IVT and MT are complimentary.

In this paper, Ferrigno et al. conducted a prospective trial in France in which 485 consecutive patients with an ICA or MCA occlusion treated by MT were enrolled. 72% of patients had combination IVT and MT therapy while 28% had MT therapy alone. Reasons to forego IVT therapy mostly included ongoing anticoagulation, recent surgery, and brain lesion with high risk of hemorrhage (including subacute stroke). Patients who recanalized prior to MT (either spontaneously or due to IVT) were excluded. The primary outcome was a dichotomized 90-day modified Rankin Scale (0-2 vs. 3+). Secondary outcomes included 0-1 on modified Rankin Scale, all-cause mortality, hematoma, and early neurological improvement.

Table: Clinical and Angiographic Outcomes According to Use of IVT prior MT before and After Propensity Score Adjustment

The primary outcome was achieved in 21.9% of patients in the MT group and 35.3% in the IVT/MT group (adjusted RR, 1.76; 95% CI 1.23-2.55). These patients were also more likely to have early neurological improvement or an excellent outcome. All-cause mortality was significantly reduced in the IVT/MT group (14.4% vs. 32.1% in the MT group, adjusted RR, 0.46; 95% CI, 0.21-0.70). Rates of hemorrhage were higher in the IVT/MT group; yet, this did not approach statistical significance.

While this is a single center study, it was well-designed and they did manage to collect a large number of patients and then retain these patients throughout the study duration. While it will be interesting to see if this is externally validated at other centers in the coming years, I can say that anecdotally, this supports what I have heard from many endovascular specialists: specifically, that they find the procedures easier and more successful post-IVT. This adds to a growing body of literature which seems to support current standard practice that continues to emphasize the importance of IVT in conjunction with MT.