• Stroke
• Economics

In a recent commentary entitled ‘Does the use of IV tPA in the current era of rapid and predictable recanalization by mechanical embolectomy represent good value?’,1 we considered the advantages and disadvantages of administering intravenous tissue plasminogen activator (IV tPA) in patients also eligible for mechanical embolectomy. This generated much discussion, underscoring the topical nature of the question. Weber et al2 have recently published an important contribution on this issue.

They retrospectively analyzed 283 consecutive patients treated with mechanical embolectomy in a tertiary neurovascular center over 14 months; data on prior IV tPA and functional outcome were available for 250 patients.2 When they compared patients treated with IV tPA and embolectomy (n=105) with patients receiving embolectomy alone (n=145), there was no significant difference in the rates of successful recanalization (Thrombolysis in Cerebral Infarction (TICI) 2b/3, 73.8% vs 73.1%, p=0.952), symptomatic hemorrhage (5.9% vs 3.5%, p=0.387), and long term favorable outcome (modified Rankin Scale (mRS) score 0–2, 35.2% vs 40%, p=0.444). Therefore, prior use of IV tPA was not an independent predictor of favorable outcome.

Moreover, at this high volume center at which 283 mechanical embolectomies were performed over 14 months, administration of IV tPA still resulted in a 36 min delay from imaging to groin puncture time. While this incurred time did not significantly impact clinical outcomes, it serves as a reminder that even polished and protocolized tPA administration comes at a cost to the clock.

Interestingly, Weber et al2 also compared patients treated directly with embolectomy alone without contraindications to IV tPA (n=70) with those treated with embolectomy alone with contraindication to IV tPA (n=75). Those treated directly without contraindication to IV tPA had significantly higher rates of favorable functional outcome (48.6% vs 32%, p=0.042). However, the significantly shorter symptom onset to end of embolectomy time between these cohorts (median 231 min (IQR 169–296) vs 325 min (323–672)) probably was an important contributor to this result.

This work by Weber et al highlights that high rates of favorable outcome are achievable in patients who are eligible for both IV tPA and mechanical embolectomy if they are treated with embolectomy alone. If patients can be treated safely, more rapidly, and just as effectively with mechanical embolectomy alone, this begs the question: should we consider changing our current treatment paradigm of bridging IV tPA followed by embolectomy?

Broeg-Morvay et al3 further consider this question by drawing from their experience of treating 1222 patients with IV tPA and/or intra-arterial treatment over 5.5 years. At this high volume center, the final decision on treatment approach was individualized on a case by case basis at the discretion of the multidisciplinary team of neurologists and neuroradiologists. In some situations (eg, a large vessel occlusion with suspicion of large clot burden), the team sometimes decided against bridging IV tPA and instead performed direct mechanical embolectomy. Of their 239 patients with anterior circulation stroke treated with mechanical embolectomy alone, they identified a subgroup of 40 patients who were treated directly with embolectomy despite being eligible for IV tPA. They then performed a multivariate matched pairs analysis with controls from the bridging IV tPA and mechanical embolectomy cohort. With results resembling those of Weber et al, for patients treated directly with embolectomy there were no significant differences in the rates of successful recanalization (TICI 2b/3, 87.5% vs 77.5, p=0.39), symptomatic hemorrhage (2.5% vs 2.5%, p=1.0), or long term favorable outcome (mRS score 0–2, 42.5% vs 42.5%, p=1.0). Notably, those treated with embolectomy alone had lower rates of asymptomatic intracranial hemorrhage (12.5% vs 35%, p=0.023) when compared with those receiving bridging IV tPA.

These two recent studies have added to the growing literature comparing patients treated with bridging IV tPA and embolectomy to direct embolectomy alone.4–6 All of these retrospective studies present a consistent message: embolectomy alone may be equally effective compared with bridging IV tPA and embolectomy for patients with large vessel anterior circulation stroke. Whether use of IV tPA is necessary prior to embolectomy has recently become an important question for our field, and a matter of significant debate. The answer to this question has the potential to significantly alter stroke management globally in two important ways. Firstly, transfer to comprehensive stroke centers for embolectomy alone may become the management of choice for patients with large vessel strokes. Secondly, the cost benefit analysis may be much more favorable for embolectomy patients without the hefty expense of IV tPA. These recent publications have energized the debate on the use of IV tPA prior to embolectomy, and have set the stage for a new randomized controlled trial for patients with large vessel occlusions who are IV tPA eligible: direct mechanical embolectomy alone versus bridging IV tPA and embolectomy. We look forward to developments to help answer this important question for our field.