February 2010 Issue: Clinical and Industry News

Invatec Receives 510(k) Clearance of Reef HP™ PTA Balloon Catheter New High Pressure Catheter Specifically Designed for Treatment of Challenging Peripheral Lesions Invatec announced that it has received 510(k) clearance from the U.S. Food and Drug Administration (FDA) to market its Reef HP™, a PTA balloon catheter, for use in peripheral high pressure dilatation procedures. The “lesion-specific” design of the balloon material is particularly useful in hard-to-dilate situations. Stefan Widensohler and Andrea Venturelli, co-founders of Invatec, commented, “The ‘lesion-specific’ design of Reef HP makes the balloon ideal for use in patients with a range of peripheral lesions, such as dialysis patients whose AV shunts often create fibrous and hard-to-dilate lesions.” The Reef HP balloon is made from Invatec’s proprietary Flexitec™ XF, an extremely durable material with a large working pressure range of up to 22 atm, offering excellent control during high-pressure procedures. The low compliant balloon offers a uniform dilatation force and strong shape retention to dilate resistive lesions with greater stability and success. Reef HP’s low-profile design enables consistent delivery and ease of crossability. The balloon is now available in a wide range of sizes in the U.S. from diameters of 4-8 mm and lengths of 20-80 mm. “We often encounter calcified and resistant lesions in peripheral vessels and in hemodialysis access interventions,” commented Robert L. Vogelzang, MD, Professor of Radiology at Northwestern University Medical School and Chief of Vascular and Intentional Radiology at Northwestern Memorial Hospital in Chicago, IL. “Invatec’s addition of a high pressure PTA balloon will aid in the successful treatment of these challenging lesions.” EKOS Corporation Supports the Dutch Randomized Trial Comparing Standard Catheter-Directed Thrombolysis vs. Ultrasound-Accelerated Thrombolysis for Thrombo-Embolic Infra-Inguinal Disease (DUET) EKOS Corporation and its Netherlands distributor, AngioCare BV, are supporting a Dutch, multi-center, randomized trial (DUET) designed to compare ultrasound (US) accelerated catheter-directed thrombolysis to standard catheter-directed thrombolysis in patients with recently thrombosed infra-inguinal native arteries or bypass grafts. Participating Dutch investigators include: Drs. Jeal-Paul de Vries and A.M. Schrijver, (St. Antonius Hospital, Nieuwegein). Additional study sites in the Netherlands are being added. Robert W. Hubert, President/CEO, said, “We are pleased to support this most important study. The hypothesis is that Ekos ultrasound accelerated thrombolysis will significantly reduce (by at least 12 hours) therapy time compared to standard thrombolysis alone without increasing complication rate.” The study is conducted in accordance with the principles of the Declaration of Helsinki and ‘good clinical practice’. (The study protocol was approved on October 13th 2009 by the Ethics Committee of the St. Antonius Hospital Nieuwegein. Written informed consent will be obtained prior to randomization.) A total of 60 adult patients with recently (between 1 and 7 weeks) thrombosed infra-inguinal native arteries or bypass grafts with acute limb ischemia class I and IIa, (according to the Rutherford classification for acute ischemia), will be randomly allocated to either group A (standard thrombolysis) or group B (Ekos ultrasound accelerated thrombolysis). The anticipated duration of recruitment will be one year. The primary endpoint is the duration of catheter-directed thrombolysis needed for uninterrupted flow in the thrombosed infra-inguinal native artery or bypass graft with outflow via at least one crural artery. Principal investigator Dr. Jean-Paul de Vries said, “Arteries occluded by blood clots mainly due to ruptured vulnerable plaques are a common serious consequence of advanced peripheral vascular disease. Current therapy involves navigating a catheter via a leg artery into the occluded section where thrombolytics re-liquefy the clot, eliminating the occlusion and re-establishing blood flow. The problem is that this process can take more than 36-48 hours, during which the patient is restricted to a bed in a hospital monitoring unit and bleeding complications increase with duration of thrombolysis. This new ultrasound-accelerated technology promises to significantly reduce the treatment time. Such a reduction, if proven, could reduce treatment costs, patient discomfort, and the risk of bleeding which is sometimes associated with these types of drugs.” The EkoSonic System is FDA-cleared for controlled and selective infusion of physician-specified fluids, including thrombolytics, into the peripheral vasculature. It is currently used to treat patients with peripheral arterial occlusions (PAO) and deep vein thrombosis (DVT) and additional applications are being investigated. For more information, visit Treat the Risk, Not the Cholesterol New Study Challenges Current Cholesterol Recommendations A new study by the University of Michigan Medical School and VA Ann Arbor Health System challenges the medical thinking that the lower the cholesterol, the better. Tailoring treatment to a patient’s overall heart attack risk, by considering all their risk factors, such as age, family history, and smoking status, was more effective, and used fewer high-dose statins, than current strategies to drive down cholesterol to a certain target, according to the U-M study. While study authors support the use of cholesterol-lowering statins, they conclude that patients and their doctors should consider all the factors that put them at risk for heart attack and strokes. The findings were released online ahead of print in the Annals of Internal Medicine. “We’ve been worrying too much about people’s cholesterol level and not enough about their overall risk of heart disease,” says Rodney A. Hayward, MD, director of the Veterans Affairs Center for Health Services Research and Development and a professor of internal medicine at the University of Michigan Medical School. The National Cholesterol Education Program recommends harmful LDL cholesterol levels should be less than 130 for most people. High risk patients should be pushed even lower — to less than 70. The U-M study took a different approach, called tailored treatment, which uses a person’s risk factors and mathematical models to calculate the expected benefit of treatment, by considering: • A person’s risk of a heart attack or stroke without treatment; • How much a statin decreases the risk; and • Potential harms from the treatment. “These are the three factors that determine the net benefit of a treatment. Our fixation on just one factor, LDL cholesterol, is leading us to often treat the wrong people,” Hayward says. In the recent study, U-M physicians who worked with Yale University School of Medicine used data from statin trials that included Americans ages 30-75 with no history of heart attack. Study authors evaluated the benefit of five years of treatment that was tailored on coronary artery disease risk factors such as age, family history, diabetes, high blood pressure, smoking status, and recently CRP (C-reactive protein). The tailored approach was more efficient (more benefit per person treated) and prevented substantially more heart attacks, strokes and cardiovascular deaths than the currently recommended treat-to-target approaches. The tailored strategy treated fewer individuals with high-dose statins and saved 500,000 more quality-adjusted life years. “The bottom-line message — knowing your overall heart attack risk is more important than knowing your cholesterol level,” Hayward says. “If your overall risk is elevated, you should probably be on a statin regardless of what your cholesterol is and if your risk is very high, should probably be on a high dose of statin,” the U-M physician says. “However, if your LDL cholesterol is high, but your overall cardiac risk is low, taking a statin does not make sense for you,” Hayward says. “If your cholesterol is your only risk factor and you’re younger, you should work on diet and exercise.” Research has increasingly emerged that questions the value of cholesterol targets and which of statins’ mechanisms is most important to preventing cardiac events. Cholesterol-lowering drugs work by blocking a key enzyme linked with LDL cholesterol production, but they initiate other changes in the body. “Statins also affect inflammation on the inside of our blood vessels which is often what causes heart attacks and strokes — it’s not just a matter of cholesterol alone,” he says. Vascular Solutions Expands Transradial Product Line with the D-Stat® Rad-Band Vascular Solutions, Inc. announces the availability of the new D-Stat® Rad-Band. This hemostatic band delivers the power of thrombin, contained in all D-Stat products, to facilitate hemostasis at the radial artery puncture site. With easy, single operator application, D-Stat Rad-Band utilizes non-occlusive pressure to keep the ulnar artery patent during compression of the radial artery. A new and improved version of the original D-Stat Radial hemostatic band, the D-Stat Rad-Band provides greater stability and easier application. Additionally, the new design incorporates a quick release feature and a larger release tab, making it easier to detach the translucent comfort pad without disrupting clot integrity. Each D-Stat Rad-Band is supplied with a clear adhesive bandage for easy visualization of the puncture site. D-Stat Rad-Band is currently available for sale in the United States through Vascular Solutions’ direct sales force. For more information, visit Published Study Demonstrates Effectiveness of Spectranetics Turbo-Booster® for Peripheral Artery Disease CELLO Study Demonstrated Significant Reduction in Artery Blockage Following Excimer Laser Ablation with Turbo-Booster® With No Major Adverse Events Spectranetics Corporation announced publication of the CELLO (CLiRpath Excimer Laser System to Enlarge Lumen Openings) study, which evaluated the effectiveness of excimer laser ablation with the Turbo-Booster for patients with peripheral artery disease (PAD) in the December issue of the Journal of Endovascular Therapy. The FDA-cleared laser treatment met its primary endpoint by reducing, on average, the percent diameter stenosis from 77.3% to 42.5% immediately post Turbo-Booster use, easily exceeding the goal of a 20% difference. Additionally, the Turbo-Booster had a low number of repeat vascular interventions, while safely improving a range of clinical and functional status assessments. The CELLO study is a prospective, 17-center study that enrolled 65 patients with claudification. Direct laser ablation was performed on above-the-knee arteries — the superficial femoral and popliteal arteries — that were at least 70% blocked. It is common for these patients to require frequent revascularization of the target artery blockage. However, the CELLO study demonstrated that 76.7% of patients did not require revascularization procedures one year post-treatment. Additionally, treatment demonstrated a strong safety profile, with no major adverse events through the six-month follow-up period. “Preventing the millions of leg amputations caused by PAD represents an urgent medical imperative,” said Dr. Rajesh Dave, principal investigator of the CELLO trial and chairman, Endovascular Medicine, Pinnacle Health Heart and Vascular Institute at Harrisburg Hospital in Harrisburg, Pa. “This study demonstrated the Turbo-Booster’s ability to produce larger lumens than what was previously achieved by excimer laser catheters alone. This may help reduce the need for aggressive adjunctive therapy, like stenting.” While adjunctive therapies remain an important part of the PAD treatment toolkit, the CELLO trial demonstrates that the Turbo-Booster may reduce the need for stent use above the knee. For instance, only 23% of the study population required them. A significant proportion of the non-stent subpopulation, 74%, did not need revascularization within one year. More than half of PAD sufferers experience leg pain, numbness or other symptoms — making it difficult to walk more than several hundred yards or perform other day-to-day activities. The CELLO study demonstrated durable objective and subjective functional improvements post-procedure, demonstrating the treatment’s sustained ability to help patient's return to normal daily activities: • Walking impairment questionnaire (WIQ): Based on this standard patient self-reported assessment, scores increased from 45.6 to 65.1 — a significant improvement in patients' perceived mobility. • Ankle-brachial index (ABI): This objective test, which assesses the ratio of blood flow to the ankle compared to the arm, significantly increased from 0.78 to 0.90 after one year. • Rutherford category: This physician-assessment score improved significantly from 2.4 to 1.3 over 12 months. The CELLO study served as the basis for the 2007 FDA clearance of the Turbo-Booster, which offers an enhancement over prior laser ablation techniques. The Turbo-Booster assists the Turbo Elite® laser catheter in delivering excimer laser energy to more of the target lesion. By rotating the laser catheter within the blood vessel, the Turbo-Booster enables ablation of more plaque than is possible with the catheter alone. Excimer laser ablation procedures for PAD deliver pulsed bursts of ultraviolet (UV) energy that vaporize blockages into tiny particles easily dissolved into the bloodstream. In contrast to the long recovery time required for bypass surgery, the excimer laser ablation procedure is performed within one to two hours with only minutes of laser time, followed by one to two days of recovery. Patients typically experience very little, if any, discomfort during the procedure. For more information, visit Sudden Death in Cocaine Abusers: Study Reveals the Role Played by the Illegal Drug Forensic pathologists have shown that over 3% of all sudden deaths in southwest Spain are related to the use of cocaine. They believe their findings can be extrapolated to much of the rest of Europe, indicating that cocaine use is a growing public health problem in Europe and that there is no such thing as “safe” recreational use of small amounts of the drug. The study, published in the European Heart Journal in January, carefully investigated all the circumstances surrounding a consecutive series of sudden deaths between 2003 and 2006. During post-mortems the pathologists tested blood and urine for traces of toxic substances, and studied the organs, focusing on the cardiovascular system and toxicological analysis; they also gathered information on substance abuse prior to death, the circumstances of the death and death scene investigations. Out of 668 sudden deaths during the study period, 21 (3.1%) were related to cocaine use; of these, all occurred in men aged between 21 and 45, and most of the cocaine-related deaths were due to problems with the heart and its related systems. Dr. Joaquín Lucena, Head of the Forensic Pathology Service at the Institute of Legal Medicine (Seville, Spain), who led the study, said: “Our findings show that cocaine use causes adverse changes to the heart and arteries that then lead to sudden death.” Dr. Lucena and his colleagues found that median levels of cocaine in blood or urine were 0.1 and 1.15 mg/L, respectively, with a range that varied widely, but which depended on a number of factors related to the drug itself (how it was taken, how people’s bodies processed it and what other substances were taken at the same time), and to the people themselves (body mass index, acute or chronic use of the drug, other underlying health issues, age and sex). They wrote, “Any amount of the drug can be considered to have the potential for toxicity due to the fact that some patients have poor outcomes with relatively low blood concentrations, whereas others tolerate large quantities without consequences.” The researchers also found that 81% of the men who died after cocaine use also smoked, and 76% had drunk alcohol. Ethanol, the intoxicating ingredient in alcoholic drinks, enhances the “high” obtained from cocaine while minimizing the subsequent “low.” However, both smoking and alcohol are associated with heart disease and Dr. Lucena said, “The combination of cocaine with either or both of these habits can be considered as a lethal cocktail that promotes the development of premature heart disease.” The study is the first to investigate the prevalence of cocaine-related sudden deaths in such a detailed and methodical way. The authors highlight the importance of this method of studying sudden deaths. “For the correct diagnosis of the sudden death, especially in young adults, it is important to use a uniform autopsy protocol, including a toxicology investigation of the blood and urine for illicit drugs,” said Dr Lucena. “Cocaine abuse is a growing public health issue in Europe and we can only monitor its prevalence by performing these detailed autopsies whenever someone dies suddenly.” In their study, the authors wrote, “The estimated number of COC [cocaine] consumers is about 12 million Europeans with an overall prevalence of 3.7% of the total adult population (15-64 years). Lifetime experience of COC is reported by more than 5% of the total adult European population in three countries: UK (7.7%), Spain (7.0%) and Italy (6.6%). The prevalence of use of COC is higher among young adults (15-34 years), with around 7.5 million young Europeans (5.4% on average) estimated as having used it at least once in their lifetime. In the year 2007, an estimated 3.5 million (2.4%) European young adults have used COC, with the highest prevalence levels, of over 3%, being found in Spain, Italy and the UK.” Professor David Hillis and Professor Richard Lange, chairman and executive vice chairman, respectively, of the Department of Medicine at the University of Texas Health Science Center (San Antonio, USA), who were unconnected with the work, wrote an editorial to accompany Dr. Lucena’s paper. They reported that the prevalence of cocaine use varied in Europe from 0.7% in Romania and Lithuania to 12.7% in the UK, but this was likely to be an underestimate. They agreed that uniform protocols were required for post-mortems on victims of sudden death, including toxicological examination of the blood and urine for illicit drugs. “Until these are accomplished, the prevalence of cocaine and other illicit drug use will be underestimated, and cocaine-related complications will not be recognized,” they wrote. “Physicians should consider the possibility of cocaine abuse in a young individual with cardiovascular disease or sudden death, especially in those without traditional risk factors for atherosclerosis. Finally, the notion that recreational cocaine use is ‘safe’ should be dispelled, since even small amounts may have catastrophic consequences, including sudden death.” New Study Shows Superiority of CareFusion’s ChloraPrep® Compared to Povidone-Iodine as a Surgical Skin Prep Prospective, Randomized Trial Shows Significantly Better Patient Outcomes in Selected Surgical Procedures within 30 Days When ChloraPrep is Used Preoperatively, Compared to Povidone-iodine Data published in The New England Journal of Medicine demonstrates that use of CareFusion’s patient preoperative skin preparation ChloraPrep® (2% chlorhexidine gluconate and 70% isopropyl alcohol) reduced total surgical site infections (SSIs) by 41%, from 16.1% to 9.5%, compared to use of povidone-iodine solution, the most commonly used preoperative skin preparation. In this prospective, randomized and well-controlled outcomes trial designed to compare the efficacy of skin antiseptics in reducing the risk of SSIs, ChloraPrep proved superior in clean-contaminated abdominal, urologic, gynecologic and thoracic surgery. SSIs are one of the most common types of health care-associated infections (HAIs); 1.7 million people suffer HAIs each year, resulting in approximately 271 deaths per day. Approximately 300,000 to 500,000 Americans develop SSIs each year, resulting in an annual cost of approximately $7.4 billion. The issue is not limited to the U.S. In the United Kingdom, one in twenty (5%) patients undergoing surgery is at risk of developing an infection and SSIs account for one-third of all deaths following surgery. Furthermore, the problem of SSIs is often the center of discussion on third-party payment policies. For example, in October 2008, the Centers for Medicare & Medicaid Services (CMS) stopped reimbursing for treatment of select health care-acquired conditions, including certain SSIs. According to CMS, certain SSIs “can reasonably be prevented” with the use of evidence-based prevention guidelines that include use of patient preoperative skin preparations and good clinical practices. This change in policy has necessitated that health care facilities focus more than ever on reducing the risk of HAIs, not just because of the human costs, but because of the financial costs. The effectiveness of ChloraPrep may be attributed to its more rapid and persistent action against microorganisms. Unlike ChloraPrep, povidone-iodine can be neutralized by blood and other organic matter, reducing its effectiveness and persistence. The residual effect of ChloraPrep allows for added clinical benefit when used as a preoperative skin preparation. In fact, the efficacy and safety of ChloraPrep for skin antisepsis are supported by more than 35 clinical studies and recommendations by 18 internationally recognized organizations or guidelines, including 11 that specifically recommend 2 percent chlorhexidine — a key ingredient in ChloraPrep. This prospective, randomized, multicenter, well-controlled outcomes clinical trial enrolled 897 patients at six hospitals in the United States; 849 patients were included in the analysis. Patients in the two groups were similar with respect to multiple factors, including demographics, other medical conditions, individual risk for infection, and both the length and type of surgery. The independent study was made possible through a research and educational grant from CareFusion. Data published in The New England Journal of Medicine demonstrates that use of CareFusion’s patient preoperative skin preparation ChloraPrep® (2% chlorhexidine gluconate and 70% isopropyl alcohol) reduced total surgical site infections (SSIs) by 41%, from 16.1% to 9.5%, compared to use of povidone-iodine solution, the most commonly used preoperative skin preparation. Findings Suggest Cardiovascular Devices Often Approved By FDA Without High-Quality Studies Pre-market approval by the FDA of cardiovascular devices is often based on studies that lack adequate strength or may have been prone to bias, according to a study in the December 23/30 issue of JAMA. The researchers found that of nearly 80 high-risk devices, the majority received approval based on data from a single study. Cardiovascular devices are increasing in number and usage. “In 2008, at least 350,000 pacemakers, 140,000 implantable cardioverter-defibrillators, and 1,230,000 stents were implanted. Although there has been recent scrutiny of evidence used in the U.S. Food and Drug Administration (FDA) drug approval process, less attention has been paid to the approval process for medical devices,” the authors write. They add that the study data on which FDA approval is based should be of high quality. “Ideally, this evidence should consist of randomized, double-blinded studies with adequate controls, sufficient duration, and thorough follow-up on prespecified primary end points without bias.” Sanket S. Dhruva, MD, of the University of California, San Francisco, and colleagues analyzed the type and quality of study evidence used by the FDA for the premarket approval (PMA) of cardiovascular devices. The authors conducted a systematic review of 123 summaries of safety and effectiveness data (SSEDs) for 78 PMAs for high-risk cardiovascular devices that received PMA between January 2000 and December 2007, examining the methodological characteristics and primary endpoints. SSEDs are intended to present a reasoned, objective, and balanced critique of the scientific evidence which served as the basis of the decision to approve or deny the PMA. The researchers found that of the 78 PMAs, 51 (65%) were supported by a single study. Of the 123 studies, only 98 SSEDs (80%) reported the number of participants enrolled. Of 123 studies in SSEDs, 27% were randomized and 14% were blinded. Fourteen percent of the studies reported did not have a primary endpoint stated. Of the 213 primary endpoints, 52% were compared with controls. “In the SSEDs, there were 157 primary endpoints for which both the number enrolled and analyzed were stated. Of these, 122 (78%) had a discrepancy between the number enrolled and those analyzed,” the authors write. One hundred thirteen discrepancies (93%) were that more patients were enrolled than analyzed. The authors add that the discrepancies between the number of enrolled patients and the number analyzed for primary endpoints may introduce bias because patients with less favorable outcomes may be lost to follow up and safety concerns may underlie this missing data. The researchers also found that of the 213 primary endpoints reported in the SSEDs, the results of 15% were noninterpretable. The most common reason was that no target goal for device performance was stated in 25 endpoints (78%), and in one instance the results were not stated. The authors state, “In some instances, endpoints were interpreted to meet their targets when they may have met only a part of them.” The authors write that there are several possible reasons why the criteria on which FDA device approval is based appear to be less rigorous than those for drug approvals. “First, device approvals are a more recent activity for the FDA, having begun in 1976 with the FDA Device Amendment, so the agency has less experience with devices than it does with drugs. Further, the last decade has brought a significant increase in the number and complexity of devices.” They add that new surgical operations do not require FDA approval, and new devices, which are nearly always implanted, are between surgical operations and drugs on the FDA approval continuum. The authors note that their study was based on the information presented in the SSEDs and some study information may be missing. However, they argue that SSEDs “should be a thorough and accurate compilation of the FDA’s critique of evidence.” “The emphasis at the FDA in the last 17 years since the Prescription Drug User Fee Act has been rapid approval of new drugs. This study suggests that the emphasis for the FDA in 2009 and beyond must be approvals based on research that meets rigorous scientific standards for evidence of benefit and lack of harm to patients. To uphold the FDA’s mission of ensuring ‘safe and effective’ medical devices, it is essential that high-quality studies and data are available.” Source: JAMA 2009;302[24]:2679-2685.