CDU Contributing Editor

WASHINGTON Although drug-eluting stents clearly captured the limelight at this year's Transcatheter Cardiovascular Therapeutics (TCT) symposium held here last month, the wide breadth of other topics in the world of interventional medicine provided numerous other important developments.

One of the more widely anticipated clinical trial results, the Cooling as an Adjunctive Therapy to Percutaneous Intervention in Patients in Acute Myocardial Infarction (COOL-MI), was reported to a large audience in one of the late-breaking clinical trial sessions in the new Washington Convention Center.

COOL-MI was the first prospective, randomized, multi-center trial designed to assess the safety and efficacy of endovascular cooling in the setting of an acute myocardial infarction (AMI). The study, which was sponsored by privately owned, venture capital-backed Radiant Medical (Redwood City, California), used its Reprieve endovascular temperature therapy system to cool patients to a target temperature of 33^o Celsius prior to a primary angioplasty procedure.

Reporting the COOL-MI results was William O'Neill, MD, chief of cardiology at William Beaumont Hospital (Royal Oak, Michigan). O'Neill said that endovascular cooling in the setting of an AMI is safe, well tolerated and can be readily integrated into existing hospital treatment pathways. However, this approach did not produce a significant difference in infarct size (heart damage) between the 199 patients in the control group who received only primary angioplasty and the 193 patients who received endovascular cooling along with angioplasty.

One of the interesting aspects of the COOL-MI trial results was that a subset analysis suggested meaningful benefit from cooling for patients who suffered an anterior or larger infarction and whose core temperature was lowered to 35^o C or less. Specifically, these patients experienced a 49% reduction in their infarct size compared to the control group, which clearly indicated that endovascular cooling was successful for some patients.

Commenting on these results, O'Neill said: "While we did not achieve the primary effectiveness endpoint, the positive dose response strongly suggests that endovascular cooling is effective in reducing infarct size when sufficient cooling is delivered prior to reperfusion." He added that "we think that there is some value in cooling anterior MI patients, particularly if we can reach a target temperature of 35^o C before reperfusion. However, we need to get these patients cooled more rapidly prior to a percutaneous intervention to achieve optimal results."

Radiant Chief Executive Officer Ken Hayes, a veteran of the medical device industry, told Cardiovascular Device Update that while he was disappointed by the results of COOL-MI, "we have learned a great deal about endovascular cooling and will use this information to design a trial that we believe will meet its endpoints."

The company, under Hayes' leadership, has been very successful in its fundraising efforts and appears to be well-financed to undertake another endovascular cooling trial. In December 2002, Radiant reported that it had closed a $22.4 million Series D preferred financing with several well-regarded venture capital groups, led by Three Arch Partners. With that closing, the company has raised about $66 million to date.

Radiant Medical's device delivers endovascular cooling with the insertion of a 7 Fr catheter through the femoral vein into the inferior vena cava. It requires skilled medical personnel to administer this therapy. Likewise, two other privately financed, venture-backed companies in the field, Alsius (Irvine, California) and Innercool Therapies (San Diego, California) use this catheter-based approach.

Another private company, Medivance (Louisville, Colorado), uses a non-invasive patient cooling device for inducing hypothermia. Its 510(k) FDA-approved Arctic Sun system consists of a control module and vest-like energy transfer pads that adhere to the patient's skin, allowing for a high rate of energy transfer into the skin through the temperature-controlled, water-filled pads.

As indicated by the COOL-MI study, one of the critical variables for the successful use of hypothermia for acute MI is rapid induction of cooling. Medivance appears to be well-positioned in this regard, as its system can be initiated by ambulance or emergency room personnel, thus beginning the process of cooling before the patient receives any coronary intervention. This may prove to be a significant competitive advantage, although to date there is no definitive clinical evidence to support this notion.

Near the end of the TCT conference, Raoul Bonan, MD, associate professor of medicine at the Montreal Heart Institute (Montreal, Quebec) reported on the safety and feasibility of the Medivance system of rapidly inducing hypothermia. Bonan said that "the early initiation of mild hypothermia as an adjunctive treatment in heart attack can be done non-invasively, safely, comfortably, and rapidly upon arrival to the emergency room to potentially reduce damage to the heart muscle. I am excited about the success of the feasibility study with this new non-invasive device and believe it will enable cooling therapy for a significant patient population." In an interview with CDU after the presentation of the COOL-MI data, Bonan emphasized the key point is that "we need to find a device that can cool the patient as soon as possible."

Based on the initial safety and feasibility results of this study, Medivance plans to initiate a larger U.S.-based feasibility study called the Chill-ER study, which will begin shortly. This five-center study will focus on the safety, feasibility and potential benefits of the early initiation of cooling.

Medivance has initiated several other clinical studies involving the use of its Arctic Sun system for inducing mild hypothermia for fever control, intracerebral hemorrhage and acute ischemic stroke. The company has raised more than $35 million over the past several years, including more than $10 million received from the sale of its patient warming business to Kimberly Clark Healthcare Group (Roswell, Georgia) in June.