Wednesday, October 8, 2014

Beyond tPA: Does Thrombectomy offer any Clinical Benefit in the Treatment of Acute Ischemic Stroke?

Your patient is a middle-aged female with multiple comorbidities who presents with sudden onset of right-sided weakness and difficulty speaking x 1 hour. Her head CT demonstrates a hyperdense left MCA. On exam, she is found to have a dense right hemiparesis, neglect and aphasia, for an NIHSS of 17. The team decides to administer tPA. An hour later, her exam is not improved. The neurology stroke team is very concerned, and wants to wheel the patient off to the neurointerventional suite for a thrombectomy.

Clinical Question:

How effective is thrombectomy in the treatment of acute ischemic stroke?

The Literature:

Endovascular therapies for the treatment of acute ischemic stroke have increased in popularity over the past several years. Several varieties of treatments exist including catheter directed thrombolysis with drugs like t-PA or mechanical thrombectomy. While IV t-PA has demonstrated benefit for functional outcome in patients with acute stroke, inclusion criteria are strict. Endovascular therapies are theorized to better deliver thrombolytic to large clots and potentially extend the therapeutic window.

In an international, multicenter prosepective single-arm study, the rates of revasculariztion in patients treated with mechanical thrombectomy with or without IV t-PA administration were measured. Revascularization was measured by blinded neuroradiologists and interventionalists based upon MR and CT angiography. A secondary output was functional outcome as defined by modified Rankin score based upon examination by an unblinded neurologist at 90 days. This study demonstrated successful revascularization in 79.2% of patients with severe adverse events in 7.4% of patients. Favorable neurologic outcome at 90 days was noted in 57.9%. Hemorrhagic conversion was noted in 18.8% of patients but only 1.5% were symptomatic.

While these numbers suggest improvement, in a later study when IV t-PA was compared to IV t-PA plus endovascular therapy (including catheter directed thrombolysis and mechanical thrombectomy techniques) the study was stopped early as the predefined criteria for futility were met. This study, published in NEJM in 2013, saw no difference in modified Rankin score of 2 or less at 90 days between the two treatment groups. No differences were seen in their predefined subgroups of severe stroke (NIHSS of 20 or greater) and less severe stroke (NIHSS 8 - 19). Additionally, the rates of hemorrhagic conversion and death were similar between the groups as well. They do note that a larger area of revascularization as noted on angiographic imaging was associated with increased proportion of good functional outcome, and that patients who underwent endovascular therapies had higher rates of revascularization compared to those who had such studies and only received IV t-PA. The authors did not comment on the significance of these differences.

Take home:

- While the available evidence shows potentially improved revascularization with endovascular techniques this has not demonstrated a translation to improved functional outcome.
- Further study with newer devices is warranted, given the signal towards favorable outcomes in revascularization.
- These studies should be undertaken in collaboration with neurologists and neurointerventionalists.
- In discussion with families, these therapies should be accurately described as “experimental” and not as anything approaching standard-of-care.

1) Pereira, V et al, “Prospective, Multicenter, Single-Arm Study of Mechanical Thrombectomy Using Solitaire Flow Restoration in Acute Ischemic Stroke,” Stroke. 2013. Vol 44; 2803-2807.

2) IMS III Investigators, “Endovascular Therapy after Intravenous t-PA versus t-PA Alone for Stroke,” New England Journal of Medicine. 2013. Vol 368(10); 983-903.

Submitted by Sara Manning, PGY-3.

1 comment:

  1. This is a nice post. Given the now 5+ postive endovascular trials, plus the updated European and American Stroke Guidelines, considering these therapies Level I A, I would consider IV + endovascular, in selected patients, standard of care. While SOC is a legal term, I think that this new generation of combination IV thrombolysis + IA device retrivers is a game changer. So, depending where one practices, it will be important to undertand the protocols and triage of select patients for these stroke patients locally or in transfer.