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Three Part Question

In [patients that present with large vessel occlusive stroke], how effective is [the Penumbra system] for [clot removal]?

Clinical Scenario

A 56 year old female presents to the emergency department after waking up with left sided weakness. She was normal when she woke up to use the bathroom in the middle of the night 4 hours ago. You wonder if she could benefit from air transport (about 30 minutes) to a stroke center which uses the Penumbra System for mechanical clot extraction.

Search Strategy

PubMed [stroke AND (thrombectomy OR embolectomy) AND Penumbra], Cochrane Library (2010)
No limits were used.

Search Outcome

20 papers were found and 3 were prospective studies relevant to the three part question

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
A. Bose, etal. Aug 2008	Subjects 18 years and older presenting within 8 hours of symptom onset of an acute neurologic deficit consistent with acute stroke and a score of TIMI 0 or 1 in a vessel accessible by the Penumbra system. Patients presenting within 3 hours had to be ineligible or refractory to IV tPA.	A prospective, single arm, independently monitored and core laboratory adjudicated trial.	23 subjects were enrolled and 21 target vessels were treated in 20 subjects by the Penumbra system. The primary endpoint was revascularization to TIMI grade 2 or 3.	Postproceudre, all 21 of the treated vessels were successfully revascularized to TIMI 2 or 3.	Subjects with vessels deamed too tortuous for access by the Penumbra System were excluded from the study rather than classified as failures - 3 subjects were excluded for this reason. Also, there was no control group; therefore, there is no comparison to recanalization rates that would have occurred spontaneously or following the standard of care.
I.Q. Grunwald, etal. April 2009	Patients presenting with symptoms consistent with acute ischemic stroke who underwent mechanical revascularization with the Penumbra System as monotherapy or adjunctive therapy at the University of Saarland from November 2005 to April 2008. Patients presenting within 3 hours had to be ineligible or refractory to IV tPA.	A prospective, non-randomised single-arm and single-center study.	29 patients were enrolled and treated with the Penumbra system. Prior to attempt at mechanical clot extraction, 12 received IV tPA, 11 received IA tPA, 3 received bridging therapy and 3 received no therapy.	Revascularization to TIMI 3 occured in 21/29 (72.4%) of subjects, to TIMI 2 in 4/29 (13.8%) of subjects and failed in 4/29 (13.8%) of subjects. 86.2% of subjects had revascularization to TIMI 2 or 3.	There was no control group; therefore, there is no comparison to recanalization rates that would have occurred spontaneously or following the standard of care. Though not necessarily a weakness, 1 author disclosed being an employee of Penumbra, Inc.
Penumbra, Inc. May 6, 2009 USA	Patients with NIHSS score greater than or equal to 8 presenting within 8 hours of symptom onset of acute ischemic stroke and with an angiographic occlusion (TIMI grade 0 or 1) of a large intracranial vessel. Patients presenting within 3 hours had to be ineligible or refractory to IV tPA. Subjects with ICH, greater than 1/3 MCA distribution stroke or severe cerebral edema were excluded.	A prospective, multicenter, single-arm study. Imaging was adjudicated for TIMI scores by an independent core safety laboratory. Data were monitored by trained internal monitors and MedPass International, a contract research organization.	125 subjects were enrolled and 125 vessels were treated using the Penumbra System.	Postprocedure 102/125 (81.6%) of treated vessels were revascularized to TIMI 2 or 3.	There was no control group; therefore, there is no comparison to recanalization rates that would have occurred spontaneously or following the standard of care. The study was done by Penumbra, Inc., raising concerns for publication bias and bias in data interpretation. However, Penumbra, Inc. used independent adjudicators for the most important results.

Comment(s)

Acute ischemic stroke is a serious cause of mortality and disability. The treatment of this disease entity is changing rapidly with changes in the IV tPA time window, the use of intra-arterial thrombolytics and now the increasing use of mechanical clot extraction devices. The first device to gain FDA approval was the MERCI (Mechanical Embolus Removal in Cerebral Ischemia) device which had a revascularization rate of 48% when used alone and 60% when used with adjunctive therapy. The Penumbra Stroke System gained FDA approval in January 2008, and is currently being used by many stroke centers. The above studies show a high rate of revascularization (greater than 80%) of occluded vessels by the Penumbra Stroke System in that subset of acute ischemic stroke patients who have evidence of arterial occlusion on imaging. Since none of these studies have control groups, it is not clear how these revascularization rates compare with spontaneous revascularization rates or revascularization rates obtained by following the prior standard of care. However, we may not ever obtain such randomised controlled trials due to obvious ehtical concerns with witholding this treatment for a control group. In addition, vessel revascularization is a surrogate endpoint for the clinical outcomes of long-term morbidity and mortality. The above studies do address morbidity and mortality as secondary endpoints but there is no control group for comparison.

Clinical Bottom Line

The Penumbra Stroke System has a high rate of vessel revascularization (>80%) and, if available, should be a consideration for any patient that presents with an acute ischemic stroke outside of the IV tPA time window, is ineligible for IV tPA, or is refractory to IV tPA.

References

1. A. Bose, etal. The Penumbra System: A Mechanical Device for the Treatment of Acute Stroke due to Thromboembolism. Am J Neuroradiol Aug 2008; 1409-13.
2. I.Q. Grunwald, etal. Revascularization in acute ischaemic stroke using the penumbra system: the first single center experience. European Journal of Neurology 2009; 16: 1210-1216.
3. Penumbra, Inc., Alameda, California. The Penumbra Pivotal Stroke Trial: Safety and Effectiveness of a New Generation of Mechanical Devices for Clot Removal in Intracranial Large Vessel Occlusive Disease. Stroke Aug 2009; 2761-8.