ISC spotlight is focused on acute ischemic stroke

By Larry Haimovitch

Medical Device Daily Contributing Writer

February 17, 2011

LOS ANGELES — The annual International Stroke Conference, (ISC) sponsored by the American Heart Association (AHA; Dallas) was held here last week. One of the key topics was the treatment of an acute ischemic stroke (AIS).

According to the AHA's "Heart & Stroke Statistics 2011 Update" AIS accounts for 691,000 (87%) of the estimated 795,000 new or recurrent annual strokes in the U.S. By comparison, hemorrhagic strokes account for only 13% of the total. Medical Device Daily estimates the global hemorrhagic market at about $1 billion worldwide, growing about 12% per year. Meanwhile, the AIS market, despite accounting for nearly seven times as many strokes, is currently generating revenue that MDD estimates at about $125-150 million worldwide.

The AIS market has grown rapidly in recent years. Two key market drivers are vastly improved devices and better imaging modalities, especiallly diffuson weighted MR imaging.

At a presentation here, Gregory Albers, MD, director of the Stanford Stroke Center (Stanford, California) discussed how better imaging technology is changing how acute ischemic stroke is managed.

"We now have the (imaging) technology . . . that will change the paradigm of stroke treatment . . . based on salvageable tissue, not time windows," said Albers.

The concept that the time window is secondary to brain tissue salvageability is significant, because the vast majority of patients cannot get treated within the narrow three-to four hour time "window of opportunity" of thrombolytic therapy. Moreover, many do not arrive in a timely fashion for the six-to-eight hour mechanical recanalization window. Many US stroke centers are now relying on images of brain pathophysiology, rather than arbitrary time frames to aid in the selection of appropriate therapies for patients who present outside the accepted stroke treatment window.

Two private, California-based companies, Concentric Medical (Mountain View) and Penumbra (Alameda) are leading the charge with evolving devices and global sales and marketing efforts. In 2004, Concentric became the first to receive FDA clearance for a mechanical thrombectomy or clot removal device, which was trade named the Merci Retrieval System. The company has made numerous modifications to its system since it first debuted, resulting in improved recanalization rates.

The results of a 1000 patient, open label, prospective, multicenter Merci registry were presented here by Marilyn Rymer, MD, from the Mid-America Brain and Stroke Institute (Kansas City, Missouri). The goal of the registry, according to Rymer was: "what does the real-world, unconstrained treatment of acute ischemic stroke look like . . ."

The data were impressive, with an 80% recanalization rate versus 64% in earlier Concentric trials, while the 90-day mortality rate declined from 38% to 33%. Two key conclusions from this study were: (1) They validate the results from earlier pivotal trials, MERCI and Multi MERCI; (2) Successful recanalization is associated with higher rates of favorable outcomes.

Concentric' s latest innovation is the Trevo stent-retriever system. Designed for quick access, rapid clot integration and retrieval, it combines a stent and a thrombus-removing catheter. The concept of this device, which has been dubbed a "stentriever," is that the stent can restore blood flow and the retriever can grab the clot and remove it.

Commercial sales began in Europe in late-2010 and early reports indicate that it is off to a strong start. The company commenced the TREVO (Thrombectomy Revascularization of large Vessel Occlusions) study in Europe in late-2010 and very recently, it began enrolling patients in TREVO-2, a randomized IDE clinical trial designed to gain domestic approval. The Trevo is being sold in Canada and a few other countries.

At a talk titled "Endovascular Therapy for Acute Ischemic Stroke Using Retrievable Stents," Aitziber Aleu, MD, from the Germans Trias i Pujols (Barcelona) discussed the results attained with these devices. 141 patients were treated with either the Trevo or Solitaire device – sold by the ev3 neuro division of Covidien (Dublin, Ireland – and the data revealed a high level of recanalization, shorter procedure times and better patient outcomes.

Covidien is the market leader in this category, the Solitaire dominates the European stentriever market. In the U.S., enrollment in the Solitaire with the Intention for Thrombectomy (SWIFT) IDE trial, with 200 patients randomized to 1:1 Merci, is nearly complete.

After this presentation, a renown stroke specialist who did not wanted to be quoted by name by MDD said "based on the data presented today, this concept looks like the real deal."

Penumbra entered the AIS market in January 2008, with its first product trade named the Penumbra System. Like the Merci Retrieval System, this product is designed for use in intracranial large-vessel occlusions, however, the Penumbra System differs because it removes the clot proximal to the thrombus using continuous aspiration.

In 2009, Penumbra introduced a new, larger internal diameter size catheter that has four times the flow rate of the company's previous largest catheter. According to a poster presented here by Donald Frei, MD, Swedish Medical Center (Englewood, Colorado) the 0.054-inch Penumbra System "can enhance aspiration efficiency and speed, leading to a shorter aspiration time and a more complete revascularization . . ."

Commenting on the Study of the Penumbra Early Evacuation Device (SPEED) trial, Frei told MDD that not only did the TIMI scores increase nicely, but that the time required for aspiration dropped 60%, from 45 minutes to only 18 minutes with the larger catheter.

Reduced aspiration or procedural time is critical, as demonstrated in a talk titled "Microcatheter to Recanalization (Procedural Time) Predicts Outcomes in Endovascular Treatment in Acute Ischemic Stroke Patients," delivered by Ameer Hassan, DO, of the Zeenat Qureshi Stroke Research Center (Minneapolis). This study of 242 AIS patients found that the procedural time ". . . appears to be a critical element for achieving favorable outcomes."

Just prior to the ISC, Penumbra announced FDA marketing clearance for its new embolic coils for treating intracranial aneurysms. According to company officials, these coils are softer and more flexible, therefore should be safer to deploy. Their flexibility allows for more dense packing, which implies that the aneurysm space should be filled more fully, potentially reducing post-procedural bleeding and the need for re-treatments. The delivery catheter is larger, thus larger coils can be delivered, which in turns means that fewer coils will be needed per case. A reduction in the number of coils should reduce the time of the procedure and thus will lower the overall cost of the procedure.

Penumbra attained CE mark for its coils in September 2010 and had already begun commercial sales. It will now begin domestic marketing with its highly regarded sales force.

In late-2010, Penumbra enrolled the first patients in its European PULSE clinical trial to evaluate a self-expanding, fully retrievable, dense mesh temporary stent designed to be deployed into a clot blocking blood flow to the brain immediate flow. The Pulse flow restoration device is designed to offer immediate flow restoration while simultaneously allowing the continued aspiration of clot using the Penumbra System.

Two other private California companies that are targeting the AIS market are venture capital-backed Reverse Medical (Irvine) and privately-funded Insera Therapeutics (Sacramento). The former has developed a suite of products, including its ReStore thrombectomy microcatheter, which received the CE Mark in July 2010. In December, Reverse achieved FDA approval to begin an IDE study in 200 patients, randomized 1:1 to the Merci device.

CEO Jeff Valko told MDD that ReStore, which he believes incorporates the only non-self expanding nitinol stent available, has several advantages. "It is extremely safe and versatile and enables super selective contrast and therapeutic infusion, flow restoration and thrombectomy." The company's other products include the RePort radial expanding guide catheter (which has CE Mark, awaiting FDA clearance), and the kink resistant ReFlex aspiration guide catheter (CE Mark and FDA approval expected soon).

Reverse plans to go direct in the U.S. and is using Getz Bros. (Hong Kong) for distribution in numerous Asian markets. They are also engaging key distributors for European markets.

Insera Therapeutics is a relatively new player in the AIS market, with its SHELTER (Stroke Help using an Endo-Luminal Transcatheter Embolus Retrieval) device. It features a nickel-titanium mesh basket which grabs the clot, which is then contained in an outer sheath. The inner part of the device has a soft, spongy tip to prevent the accidental puncturing of blood vessels.

The engineering and development of this product was partially funded by the National Science Foundation's (NSF; Arlington, Virginia) Small Business Innovation Research program. According to an NSF press release, SHELTER is the first platform to filter and remove clots, the first to entrap the clot from both its near and far ends and the first capable of accessing small vessels in the brain. Critically, the technology can be custom-fit for the specific length and diameter of a patient's clot, a personalized approach that may improve treatment success.

The device has been used in several human cases in India and the company very recently began working to attain CE Mark approval. Insera hopes to initiate a domestic clinical trial in late-2012.

2011 International Stroke Conference

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