"ACT I represents a major step toward bringing the benefits of minimally- invasive procedures to all patients at risk of stroke due to carotid artery disease," said Robert B. Hance, president of Abbott Vascular Devices, a division of Abbott. "The ACT I trial sets the stage for a new phase in helping patients avoid strokes and live longer, healthier lives."

Ken Rosenfield, M.D., director of Cardiac Invasive Services at Massachusetts General Hospital and co-principal investigator of ACT I, said, "ACT I is designed to assess the benefits of carotid stenting for those patients at risk of stroke for whom surgery and/or medication remain the only options. This is truly a landmark study that should have an immediate, positive impact on patients' lives."

Stroke and Carotid Artery Disease
Stroke represents the third leading cause of death and the number one cause of disability in the United States, with more than 700,000 Americans suffering strokes each year(i). Almost one in three patients who suffer a stroke will be permanently disabled(ii), and one in four will die within one year. The estimated direct and indirect economic impact of stroke in 2004 in the United States was $53.6 billion(iii). Nearly 90 percent of all strokes stem from insufficient blood supply to the delicate tissue of the brain, a condition caused by narrowing or blockage of cerebral blood vessels(iv).

Approximately one-fourth of all strokes are caused by carotid artery disease(v), a condition that reduces the blood flow through the carotid arteries to the brain. In these patients, lesions develop on the walls of the carotid arteries, causing the vessels to narrow. These lesions can then become dangerous sources of plaque that may break free from the arterial walls and clog smaller vessels within the brain, resulting in an ischemic stroke.

Therapies for Preventing Strokes
Approximately 75 percent of all stroke patients are asymptomatic, meaning that they are at increased risk for stroke but have not recently (or have never) displayed symptoms(vi). Studies indicate that a number of factors can increase the risk of stroke, including increasing age, high blood pressure, high cholesterol, diabetes and obesity. Even when no symptoms are displayed, physicians can diagnose patients at risk of stroke from carotid artery disease by using one or more tests -- such as an ultrasound. Once significant carotid artery disease has been confirmed, there currently are only two accepted treatment options among asymptomatic patients who are healthy enough to undergo surgery: conventional carotid artery surgery (called carotid endarterectomy or CEA), or medication and lifestyle modification.

During a CEA, patients are typically placed under general anesthesia, and their diseased carotid arteries are opened with an incision in the neck. Plaque from the arteries is then scraped from the vessel wall and removed. Patients who have this surgery reduce their risk of stroke by more than 50 percent versus patients who do not undergo surgery. Even after successful surgeries, however, patients continue to face an ongoing risk of stroke or death of 5.1 percent in the first five years post-procedure.

Patients who decline or are ineligible for surgery are normally placed on a battery of medications and are given lifestyle modification counseling to help reduce their risk of stroke. Such patients face an ongoing stroke risk of 11.0 percent during their first five years on medical therapy(vii).

Carotid artery stenting (CAS), a third, highly promising treatment option, was recently approved by the FDA for a very limited group of patients who require immediate intervention to prevent a stroke, but for whom surgery presents too high a risk. Currently, only one manufacturer's carotid stent device has received approval and is available on the market. Abbott submitted its Xact® Carotid Stent System and Emboshield® Embolic Protection System for FDA approval to treat this patient group in September 2004, and the device is currently under review.

Physicians use these minimally invasive devices to treat carotid artery disease by placing a stent in the carotid artery to restore unrestrained blood flow to the brain. The stent is brought into position in the carotid artery via thin catheters that are threaded through the vascular system from a small access site -- typically made in the femoral artery in the groin. A special device called an embolic protection filter is opened up like an umbrella downstream from the stenting procedure to protect the patient's brain by catching emboli (plaque) that may be dislodged during the procedure.

Carotid artery stent systems have not yet been FDA approved for use in asymptomatic patients healthy enough to undergo surgery (who comprise approximately 75 percent of patients at risk for stroke) due to lack of clinical data. Medication or surgery and medication combined remain the only approved options for this patient population(viii).

ACT I: Trial Design
ACT I, which stands for "Carotid Angioplasty and Stenting vs. Endarterectomy in Asymptomatic Patients with Significant Extracranial Carotid Occlusive Disease Trial," will compare CAS to CEA in asymptomatic patients who are at standard risk for surgery. This randomized trial is designed to establish the non-inferiority of CAS to CEA in this patient population. The CAS arm of the trial will use Abbott's Xact Carotid Stent System and Emboshield Embolic Protection System, which were designed together specifically for carotid stenting procedures. All patients enrolled in the trial will receive appropriate medications and lifestyle modification counseling during the study.

The trial will involve up to 50 hospitals in the United States and approximately 1,500 patients, with primary endpoint data submitted after one year of patient follow-up. The trial's primary endpoints are as follows: (1) 30-day major adverse event (MAE) rates combining stroke, death and myocardial infarction (heart attack); and, (2) ipsilateral strokes (those occurring on the same side as the therapy) between 31 and 365 days. The trial's secondary endpoints include target lesion revascularization rate (the rate at which the vessel must be re-opened), device/procedural success rates, cumulative composite morbidity (nerve damage, wound complications, general anesthetic complications, etc.), and long-term ipsilateral stroke rates through five years of follow-up.

"Through ACT I, Abbott is taking an essential step in evaluating potential options for stroke prevention," said Jon Matsumura, M.D., vascular surgeon at Northwestern University and co-principal investigator of ACT I. "This multicenter, prospective, randomized, controlled clinical trial demonstrates Abbott's leadership in exploring new treatments for stroke prevention. These types of trials are the foundation of evidence-based medicine and assist physicians and patients in critical decision-making. The initiation of ACT I starts a new phase in stroke prevention research."

ACT I: Economic and Quality of Life Assessments
In addition to comparing clinical impacts, ACT I will assess the relative economic and quality of life factors associated with CAS and CEA. The trial will quantify not only device and facility costs, but also the total costs to the health care system of each treatment option. Such information will help to support informed decision-making in procedural reimbursement and treatment selection. This information is especially important, given that stroke is the leading cause of inpatient Medicare expenses for long-term care(ix).

In examining patient lifestyles after CAS and CEA procedures, ACT I will evaluate the speed and quality of patients' recoveries, as well as how quickly and easily they return to their regular routines.

"CEA and CAS are radically different in the way they impact patients' lifestyles and ability to function," said Dr. Rosenfield. "ACT I will provide key decision makers a clearer picture of how these procedures affect not only our patients' health, but also their broader lives."

The Technologies: The Emboshield Embolic Protection System
In the United States, the Emboshield Embolic Protection System and the Xact Carotid Stent System are investigational devices not approved for sale. Both the Emboshield and the Xact have CE Mark approval for distribution in European Union and European Free Trade Association markets.

Emboshield is one of the latest innovations in filter-based embolic protection devices and was developed to minimize the risk of distal embolization (the release of emboli into the bloodstream), which may lead to ischemia, stroke, heart attack and potentially death. Recently, Emboshield was proven to be the most effective filter at preventing embolization in an in-vitro model among the carotid embolic protection devices studied by independent scientists(x).

Emboshield is the only filter that moves freely on a proprietary wire, Barewire™, and physicians can select from a range of Barewires for use in different anatomies and procedures. Unlike other protection devices that are fixed to the wire, Barewire technology more closely resembles the guide wires to which physicians are accustomed when performing interventional procedures. This similarity to current practice is intended to provide optimal deliverability and to make Emboshield easier to use. This may, in turn, help minimize patient risk.

The Technologies: The Xact Carotid Stent System
Designed specifically for carotid arteries, the Xact self-expanding nitinol stent offers three important features for successful carotid revascularization: a closed cell configuration that is designed to avoid filter snagging during retrieval; a high coverage ratio intended to reduce the release of stroke-generating plaque; and straight and tapered stent constructions intended to enhance conformance to the carotid anatomy. The Xact stent also offers Freestyle Technology™, which helps ensure exact placement of the stent at the targeted site.

About Abbott
Abbott is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs more than 60,000 people and markets its products in more than 130 countries.

Abbott's news releases and other information are available on the company's Web site at http://www.abbott.com .

(i) American Heart Association, Heart Disease and Stroke Statistics - 2004 Update, Dallas, TX: American Heart Association. 2003:1-52. (ii) Dion J. Journal of Vascular Interventional Radiology 2004; 15:S133-S141. (iii) American Heart Association, Heart Disease and Stroke Statistics - 2004 Update, Dallas, TX: American Heart Association. 2003: 14, 15. (iv) American Heart Association, Heart Disease and Stroke Statistics - 2004 Update, Dallas, TX: American Heart Association. 2003:1-52. (v) Higashida R, Meyers, P, Phatouros C, et al. Journal of Vascular Interventional Radiology 2004; 15:E1-E24. (vi) American Heart Association, Heart Disease and Stroke Statistics - 2004 Update, Dallas, TX: American Heart Association. 2003:1-52. (vii) Executive Committee for the Asymptomatic Carotid Atheroschlerosis Study. Endarterectomy for asymptomatic carotid artery stenosis. Journal of the American Medical Association. 1995;273:1421-1428. (viii) American Heart Association, Heart Disease and Stroke Statistics - 2004 Update, Dallas, TX: American Heart Association. 2003:1-52. (ix) Dion J. Journal of Vascular Interventional Radiology. 2004; 15:S133-S141. (x) Muller-Hulsbeck, et al. Journal of Vascular Interventional Radiology. 2003; 14:613-620.