Mechanical Thrombolysis in Acute Stroke 

At present, intravenous (IV) tissue-type plasminogen activator (tPA) is the only medical therapy approved for treatment of acute stroke in the United States. Almost 50% of patients treated with tPA in the trial by the National Institutes of Neurologic Disorders and Stroke (NINDS) achieved essentially full recovery.^[1]

However, subgroup analyses of the NINDS data showed that patients with severe strokes had only an 8% likelihood of achieving clinically significant improvement with tPA.^[2] The poor outcome in these patients has inspired the search for acute-stroke treatments that are more effective than tPA.

Mechanical treatments include the use of catheters to directly deliver (during angiography) a clot-disrupting or retrieval device to a thromboembolus that is occluding a cerebral artery. Most devices are used in cerebral vessels that are 2-5 mm.

Mechanical thrombolytic devices can remove a clot in a matter of minutes, whereas pharmaceutical thrombolytics, even those delivered intra-arterially, may take as long as 2 hours to dissolve a thrombus.^{[3, 4]}

Concentric MERCI Retrieval System

The Concentric MERCI (Mechanical Embolus Removal in Cerebral Ischemia) Retrieval System is a corkscrew-like apparatus designed to remove clots from vessels in patients experiencing an ischemic stroke (Concentric Medical, Inc, Mountain View, Calif) (see the images below).^{[5, 6]}

The corkscrew resides in the catheter tip, which shields it from the wall of the vessel until it is ready to be burrowed into the clot. Once lodged in the clot, the device and clot are withdrawn from the vessel. The Retriever has received approval from the US Food and Drug Administration (FDA) for use in patients with persistent vessel occlusion after IV tPA.

In a study of patients with ischemic stroke, recanalization occurred in 55% of patients who were treated with a MERCI device alone and in 68% of patients who were treated with a MERCI device plus adjuvant treatment. (These figures were the combined results from different models of the device.)

Symptomatic ICH occurred in 9.8% (16/164) of patients overall, and a favorable outcome, (a modified Rankin score of 2 or less), was seen in 36% of patients at 90 days.

A favorable outcome was seen in 49.1% of revascularized patients, versus 9.6% of those without revascularization. The mortality rate in patients with revascularization was approximately half that of patients with no revascularization (24.8% versus 51.9%, respectively).^[7]

The NINDS has funded a randomized trial of the MERCI Retriever compared with medical therapy as long as 8 hours after symptom onset. This trial is called Magnetic Resonance and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE). The effects of therapy will be stratified by the presence of a penumbra on magnetic resonance imaging (MRI) at randomization.

Penumbra system

The FDA approved the Penumbra System (Penumbra, Inc, Alameda, Calif) in 2007 to open vessels in patients with ischemic strokes (as demonstrated in the image below). Patients who have received IV tPA can be treated. The device uses aspiration to remove the clot.

Initial results for one study, reported at the International Stroke Conference in New Orleans in February 2008, found that the recanalization rate for patients treated with the Penumbra system, measured for the target vessel, was 81.6%. Symptomatic intracranial hemorrhages occurred in 11.2% of patients. A modified Rankin score of 2 or less at 90 days was seen in 25% of patients.^[8]

Snarelike devices

In anecdotal reports, interventionists used retrieval devices to remove thrombi from cerebral vessels. Snares, such as the Neuronet snare (Guidant Endovascular, Santa Clara, Calif), have been developed specifically for use in the treatment of strokes. These devices, which have not yet been evaluated in acute-stroke trials, are simple in design and do not require the clot to be amenable to emulsification.

EKOS ultrasound device

As its name suggests, an ultrasound thrombolytic infusion catheter (EKOS Corporation, Bothell, Wash), seen in the images below, combines the use of a distal ultrasound transducer with infusion of a thrombolytic agent through the microcatheter.^[9]

Ultrasound changes the structure of the clot to temporarily increase its permeability while providing an acoustic pressure gradient to move the drug into the clot to speed its dissolution.

The EKOS product has not yet received FDA approval for use against acute stroke. It is currently being studied to determine its efficacy in such treatments.

There is currently too little data available to compare the performance of mechanical thrombolytic devices with intra-arterial lytics in the treatment of acute stroke. Devices could potentially retrieve large clots that pharmaceutical agents are not able to lyse successfully, and large hemorrhages may occur less frequently with device use. However, the ultimate effects of these devices on outcome are unclear. In the end, clots may best be treated with a combined approach using various devices, lytics, and antithrombotics.

Because many patients with stroke do not arrive at the hospital early enough to receive IV tPA, mechanical embolectomy potentially extends the treatment window. Although a pooled analysis of patients with anterior circulation strokes adjusted for baseline factors in the MERCI/Multi MERCI trials showed a strong trend toward fewer independent outcomes with later reperfusion times, 40% of the patients reperfused at ≥6.9 hours achieved independent functional outcomes.^[10] Patients who are not thrombolytic candidates, such as those that have had a recent surgical procedure, can be considered for treatment with mechanical embolectomy.

In addition, patients treated with IV tPA may be considered for treatment of residual clot. We must consider the referral of potential treatment candidates for mechanical embolectomy to stroke centers that are equipped to perform the procedure.