Clinical and Industry News

New VerifyNow Test Can Determine if Daily Clopidogrel is Working to Block Platelets as Protection Against Heart Attack and Stroke Blood Test Can Identify the Up to 30 Percent of Clopidogrel Users Who Do Not Respond Adequately; Test Can Also Help Determine if It’s Safe to Undergo Surgery A new blood test for measuring the effects of one of the most commonly prescribed drugs in the United States has just been cleared by the Food and Drug Administration. The drug is Plavix® (clopidogrel), taken by almost 10 million Americans. VerifyNow P2Y12 is a blood test specifically designed to measure the effects of clopidogrel on platelets (clopidogrel inhibits platelet function). Numerous studies have demonstrated the benefit of clopidogrel, but new research also indicates that from 5 to 30 percent of patients do not respond adequately to the drug. The medical consequences can be dramatic: Patients who are nonresponsive to clopidogrel are at much greater risk for a serious cardiovascular event that includes not only heart attack or stroke, but also coronary stent restenosis. The most recent study linking response to clopidogrel with patient outcomes was published in the September 2005 Journal of the American Medical Association. It suggests that response to clopidogrel is an important factor in reducing cardiovascular events after coronary intervention. Because of these concerns, nonresponsiveness to clopidogrel and other antiplatelet agents has become a subject of much attention in the medical community. Increasingly, physicians are beginning to focus more aggressively on how this clinical problem should be monitored and managed. We’re now developing an understanding that, as for every other medicine, not all patients respond equally well to clopidogrel, said Daniel Simon, MD, associate director of interventional cardiology at Boston’s Brigham and Women’s Hospital. We don’t prescribe other drugs and just assume they’re working. We test for the effects of cholesterol drugs and blood pressure drugs, we monitor response to the anticoagulant warfarin. We need to start adopting a similar paradigm for antiplatelet therapies such as aspirin and clopidogrel. Monitoring clopidogrel response also has economic implications. A month’s supply of the drug costs more than $100. Given the number of patients who may not respond, this could represent more than $1 billion in health care spending without any corresponding benefit. Clopidogrel is a very effective medication for preventing strokes and heart attacks, noted Mark Alberts, MD, professor of neurology at Northwestern University Feinberg School of Medicine and director of the stroke program at Northwestern Memorial Hospital in Chicago. However, in a certain percentage of patients, the blood-thinning effects of clopidogrel may not be optimal. The VerifyNow test provides physicians with an important tool to help identify these patients and plan appropriate therapy. In less than 15 minutes, VerifyNow gives an easy-to-understand result that indicates if a person is responding effectively to clopidogrel or not. The test is inexpensive and is covered by Medicare as well as by many insurance providers. VerifyNow P2Y12 has implications in other areas of medicine as well. For example, the test can help doctors determine if a patient can safely undergo surgery. Medical guidelines recommend that a person stop taking clopidogrel for five days prior to an operation to enable clotting function to return to normal and to reduce the risk of excessive bleeding during or after a procedure. However, this means that surgery often must be delayed. Furthermore, withholding clopidogrel can put patients at increased risk for a heart attack or stroke while they are waiting to undergo their operation. Such a situation occurred recently when former President Clinton needed heart surgery. His doctors waited several days before performing the bypass operation to ensure that the antiplatelet drugs he had been taking were cleared from his system. The clopidogrel test removes the guesswork about whether it’s safe to go to surgery, said Christopher Cannon, MD, associate physician in the cardiovascular division of Brigham and Women’s Hospital, and a leading cardiovascular researcher. Having information about clotting status allows us to proceed with the operation the day that function returns to normal, rather than routinely waiting five days in every case. This could dramatically reduce surgical delays for patients taking clopidogrel. Medicure Inc.: FDA Grants MC-1 Fast Track Designation The U.S. Food and Drug Administration (FDA) has granted Medicure’s cardioprotective drug, MC-1, Fast Track designation as a treatment to reduce cardiovascular and cerebrovascular events associated with ischemic and/or ischemic reperfusion injury in patients undergoing percutaneous coronary interventions, coronary artery bypass graft surgery or experiencing an acute coronary syndrome. The application for Fast Track designation was submitted based on the demonstrated clinical efficacy and safety of MC-1 and the unmet medical need the drug addresses. The FDA identified coronary artery disease requiring intervention as a life-threatening disease, and the need for a drug to treat heart attacks and strokes as the rationale for designating MC-1 as a Fast Track product. Under the FDA Modernization Act of 1997, the Fast Track program was implemented to facilitate the development and expedite the review of new drugs that are intended to treat serious or life-threatening disease, and that demonstrate the potential to address unmet medical needs. Fast Track-designated drugs are eligible for priority review (6 months versus the average 12 months) and/or the review of portions of the marketing application prior to the completion of the final registration package. MC-1 is a naturally occurring small molecule that reduces the amount of damage to the heart following ischemia and/or ischemic reperfusion injury. Studies with MC-1 suggest that it does this by protecting cardiomyocytes. Since cardiomyocytes are essential for normal heart function and do not regenerate themselves following an ischemic event, their preservation is key to minimizing ischemic damage and maintaining proper heart function. MC-1’s cardioprotective properties were demonstrated in the Phase II MEND-1 study in patients undergoing percutaneous coronary interventions. MC-1 is currently being investigated in the Phase II/III MEND-CABG study in patients undergoing coronary artery bypass graft surgery, and enrollment was completed in July with results expected in fall 2005. The MEND-CABG trial is evaluating the cardioprotective and neuroprotective effects of MC-1 in high-risk coronary artery disease patients undergoing CABG surgery. The Phase II component of the Phase II/III trial enrolled 900 patients at 42 investigational sites located throughout Canada and the United States. The purpose of the trial is to detect the clinical efficacy of MC-1 on mortality and morbidity endpoints. The primary endpoint of this placebo-controlled, double-blinded trial is the reduction in combined incidence of all vascular deaths, nonfatal myocardial infarction and nonfatal cerebral infarction, up to and including postoperative day 30 (POD 30). To assess the efficacy, the event incidence in each of two dose groups 250 mg and 750 mg per day will be compared to the incidence level in the placebo group. Secondary efficacy endpoints include evaluating the effect of MC-1 at postoperative day 90 (POD 90) on the same composite of events, as well as the individual components of the composite (i.e., vascular death, nonfatal heart attack and stroke) at POD 4, 30 and 90. Other secondary endpoints being measured during the trial include cardiac tissue damage as determined by CK-MB and neurological function. Safety and tolerability will also be assessed. Physician Pay-for-Performance Programs May Produce Little Gain in Quality Paying clinicians to reach a common, fixed performance target may produce little gain in overall quality, and may largely reward those with higher performance at baseline, according to a study in the Journal of the American Medical Association. The number of health plans and purchasers in the United States that have adopted pay-for-performance mechanisms for quality improvement is growing rapidly. However, most of these programs are in the early stages of trial, evaluation and adjustment. Although there is intense interest in and optimism about pay-for-performance programs among many policy makers and payers, there is little published research on pay-for-performance in healthcare. There have been a few studies demonstrating that pay-for-performance leads to improved quality of care. Meredith B. Rosenthal, PhD, of the Harvard School of Public Health, Boston and colleagues, conducted a study on the impact of a prototypical physician pay-for-performance on quality of care within one of the nation’s largest health plans, PacifiCare Health Systems. In 2003, PacifiCare began paying its California medical groups bonuses according to meeting or exceeding ten clinical and service quality targets. The researchers examined the performance of California medical groups that were subject to pay-for-performance, and a comparison group in the Pacific Northwest (Oregon and Washington). Quality improvement reports were included from October 2001 through April 2004 issued to approximately 300 large physician organizations. There were three process measures of clinical quality: cervical cancer screening, mammography and hemoglobin A1c testing. The researchers found that clinical quality scores improved as follows: for cervical cancer screening, 5.3 percent for California versus 1.7 percent for Pacific Northwest; for mammography, 1.9 percent versus 0.2 percent; and for hemoglobin A1c testing, 2.1 percent versus 2.1 percent. Compared with physician groups in the Pacific Northwest, the California network demonstrated greater quality improvement after the pay-for-performance intervention only in cervical cancer screening (a 3.6 percent difference in improvement). For all 3 measures, physician groups with baseline performance at or above the performance threshold for receipt of a bonus improved the least, but garnered the largest share of the bonus payments. In the first year of its quality incentive program (QIP), the plan paid $3.4 million of a potential bonus pool of $12.9 million. Three-quarters of the 172 physician groups eligible at some point during the year for the program received some funds from the bonus pool. We also observed that few groups reached a majority of targets, consistent with the low correlation in performance across clinical areas that has been observed in other studies. Physician groups whose performance was initially lowest improved the most, whereas physician groups that had previously achieved the targeted level of performance improved the least. Unlike quality improvement, which followed an inverse relationship to baseline performance, bonus dollars were garnered in direct proportion to baseline performance. Physician groups whose performance was above the bonus threshold at baseline captured 75 percent of bonus payments on average across the 3 quality domains we examined, despite their limited improvement, the authors write. Our findings give rise to a number of speculations about the effects of pay-for-performance. First, groups with baseline performance already above the targeted threshold appeared to understand that they needed only to maintain the status quo to receive the bonus payments. More surprising, perhaps, is that low-performing groups improved as much as they did, given that their short-run chances of receiving a bonus were likely to be low. One possibility is that the groups viewed the QIP as a larger signal of a changing environment in which they would face increasing pressure to improve their care systems and decided to begin moving in that direction. Paying explicitly for quality improvement might alter the incentives for high-performing and low-performing groups, distribute bonus dollars more toward the latter group, and possibly increase the overall impact of pay-for-performance. The authors add that one possible reason that the QIP failed to yield a greater response is that the financial rewards for quality were too low to motivate substantial departures from the underlying trend in quality improvement. Per enrollee, the maximum annual bonus was a relatively modest $27, or about 5 percent of the professional capitation amount. Moreover, PacifiCare accounts for only about 15 percent of the average group’s revenue. PacifiCare’s QIP, like most current pay-for-performance programs, should be viewed as a first step in the direction of aligning payment incentives with health system quality goals. Realization of the full potential of pay-for-performance to reduce the persistent gap between evidence-based and actual practice will require that payers adapt their incentive strategies as evidence to support best practices accumulates. The principle lesson we derive from this experience is that incentive design matters. The accumulating evidence from the continuing experimentation with pay-for-performance in the market will highlight these initial findings and other potential design lessons, the researchers conclude. From: JAMA. 2005;294:1655-1663. W. L. Gore & Associates Acquires Bioactive Heparin Technology Company W. L. Gore & Associates, Inc. (Gore) has acquired Carmeda AB, a Sweden-based manufacturer of the most clinically proven, hemocompatible surface coating for medical devices. Carmeda has been a strategic supplier to Gore of heparin and heparin-related technologies for nearly ten years. The Carmeda AB leadership team and workforce will remain in its existing facility in Upplands Vasby, Sweden. Gore utilizes the CBAS coating in its Vascular Graft. The CBAS coating provides unique hemocompatibility by minimizing clot formation on the inside surface of Gore-Tex Propaten Vascular Grafts. The Gore-Tex Propaten Vascular Graft is commercially available to physicians in Europe and elsewhere outside the United States. It is an investigational device in the United States, limited by U.S. law to investigational use only. A U.S. clinical study under a Food & Drug Administration IDE is currently in progress. Medtronic Begins 8,000-Patient ENDEAVOR V Registry Medtronic, Inc. announced the start of the 8,000-patient ENDEAVOR V post-market registry, a prospective, multicenter study in Europe, Asia and other areas outside the United States. This registry is designed to evaluate real-world use and clinical performance of the Medtronic Endeavor drug-eluting coronary stent system in patients with coronary artery disease. The stent received approval from the European Commission in July 2005. The Principal Investigators for the ENDEAVOR V registry are Prof. Martin T. Rothman, The London Chest Hospital, London, United Kingdom, Prof. Chaim Lotan, MD, head of the Hadassah University Hospital Heart Institute, Jerusalem, Israel, and Prof. Ian Meredith, MD, Monash Medical Centre, Melbourne, Australia. Approximately 200 clinical centers will be involved in the study. The first patient enrollment occurred recently in Austria. We performed a multivessel intervention in a patient with two complex lesions, said Prof. Dietmar Helmut Glogar, MD, Medizinische Universitat Wien, Vienna, Austria, who implanted four Endeavor stents during the procedure. The crossing potential of the Endeavor stent in both very tortuous and calcified lesions was excellent. The end result of the procedure was very good, and the patient was able to avoid bypass surgery. The primary end point for ENDEAVOR V is major adverse cardiac events (MACE) at one year. Secondary end points include MACE at 30 days and 6 months, stent thrombosis rate at 24 hours, from 2-30 days and at 30 days or longer, and procedural, clinical and lesion success rates. The Endeavor drug-eluting stent is made of a cobalt alloy and has a unique modular architecture designed to enhance deliverability over standard bare metal stents. In addition to the proprietary drug compound ABT-578, the Endeavor stent is coated with phosphorylcholine (PC), a polymer designed to simulate the outside surface of a red blood cell and to mimic the structure of the natural cell membrane. Older Patients with Acute Coronary Syndromes Not Getting Recommended Treatment A review of more than 56,000 cases of acute coronary syndromes reveals that older patients are less likely to receive treatment recommended by guidelines, even though they benefit as much or more than younger patients when the recommended treatment is provided, according to a study in the October 18, 2005 issue of the Journal of the American College of Cardiology. Our study is unique in that it describes early use of therapies, defined as those within the first 24 hours, and is targeted at guideline-recommended care. In fact, although improvements have been realized in adherence to discharge therapies, we found early use of therapies was where some of the largest differences between young and old patients remained. In addition, we demonstrated an inverse relationship between the number of evidence-based therapies applied and in-hospital death in young and old subgroups alike. Although any observational analysis may suffer from residual confounding, we demonstrate that older patients, as a group, benefit equally from guideline-recommended care, said Karen P. Alexander, MD, from the Duke University Medical Center in Durham, North Carolina. This analysis used data collected as part of an effort to document the real-world treatment of patients with acute coronary syndromes, including unstable angina and heart attacks. Information on 56,963 patients treated at 443 hospitals across the U.S. was collected for the CRUSADE National Quality Improvement Initiative from January 2001 to June 2003. CRUSADE is an initiative that is designed to increase the practice of evidence-based medicine for patients diagnosed with non-ST segment elevation acute coronary syndromes (NSTE ACS). The patients were split into four age groups (younger than 65, 65 to 74, 75 to 84, and 85 or older). Rates of rapid use of drugs that reduce or prevent blood clots decreased with age. Elderly patients were also less likely to undergo diagnostic catheterization procedures, angioplasty or coronary artery bypass surgery. Most medications prescribed at hospital discharge were similar across all age groups; however, elderly patients were less likely to receive clopidogrel or cholesterol-lowering drugs. The differences were apparent even after adjusting the treatment data to take into account known contraindications to treatment and other diseases that might have influenced treatment decisions. The researchers also noted that although death rates and complications rose with advancing age, elderly patients who received more recommended therapies were less likely to die than those who did not. Dr. Alexander said that progress is being made toward providing recommended treatment to patients of all ages, but this study shows there is more work to be done. Awareness of gaps is the first step in narrowing them. Further work on lipid-lowering in the very elderly, and early identification of acute coronary syndrome symptoms in the aged, are areas which will benefit from continued work, she said. Dr. Alexander noted that hospitals volunteer to participate in CRUSADE and they receive web-based educational sessions about the treatment of acute coronary syndromes. The study focused on the specific treatments recommended by ACC/AHA guidelines, so it did not collect data on aspects of care or details of other illnesses patients may have had. However, she said that enrollment was specific to patients with an acute coronary syndrome, and that the large number of hospitals and patients should provide a fairly representative view of current clinical practice. H. Vernon Anderson, MD, FACC, from the University of Texas Health Science Center at Houston, who wrote an editorial in the journal with Richard G. Bach, MD, FACC from the Washington University Medical Center in St. Louis, Missouri, said this report is part of an extremely important effort to understand how clinicians are actually treating heart patients. There’s a reluctance to be’aggressive’ in older people, that somehow they are more fragile, that they have greater problems with medications, that you have to be somehow more gentle about doing things. And I think here are data that suggest that just isn’t true; that in fact, while the elderly do have increased risks, on the other hand the potential benefits of treatment are greater, too. That’s a strong argument that we should be treating the elderly very much more like we are treating the non-elderly. That in fact they are going to get a net benefit out of the treatment, Dr. Anderson said. St. Jude Medical Announces U.S. Launch of New Technology for Placing Guidewires in Coronary Vessels Venture Wire Control Catheter Gives Physicians Turns Up to 90 Degrees, More Control to Penetrate Challenging Lesions St. Jude Medical, Inc. announced the U.S. launch of the Venture Wire Control Catheter, designed to give cardiologists more control and support as they steer guidewires during interventional cardiology procedures. The Venture catheter features a deflectable tip that can bend up to 90 degrees, allowing for guidewire placement in hard-to-reach branches of the coronary and peripheral anatomy. Physicians turn a control knob on the handle to mechanically deflect the tip and precisely direct the catheter toward a specific location. The catheter’s coiled torque shaft provides back-up support, giving the physician more focused pushability and providing greater control when crossing a full range of lesions, from narrowed vessels to chronic total occlusions, where lesions completely block the vessel. With Venture, some patients may now be treated through minimally invasive procedures, rather than having to undergo bypass surgery. In the U.S., more than 1 million catheter-based coronary procedures are performed each year. The most common challenges for these procedures include highly angulated takeoffs (up to 90 degrees), arteries with multiple turns, and chronic total occlusions. The catheter's deflectable tip allows for efficient navigation of angles, adjusts for complex turns in the artery and provides guidewire support when attempting to cross chronic total occlusions. It is compatible with all standard 0.014 inch guidewires and accommodates wire exchanges, if needed. St. Jude Medical expanded its cardiology portfolio through the April 2005 acquisition of Velocimed, a Minnesota-based company with three product platforms for interventional cardiology, including the Venture catheter. The Venture catheter is also commercially available in Europe and Canada. Stents Open Totally Occluded Carotid Arteries Stenting restored blood flow in stroke patients who had complete blockage in a carotid artery, according to a preliminary report in Stroke, the journal of the American Heart Association. Researchers studied patients who had a stroke caused by total blockage of one of the internal carotid arteries. In 23 of 25 patients (92 percent), the stent restored blood supply when the blockage extended into the skull, said Ken Uchino, MD, assistant professor of neurology at the University of Pittsburgh. Historically, about 40 percent of patients with strokes caused by total blockage of the internal carotid artery suffer severe disability and 20 percent of patients die within three months of stroke, he said. Of the patients who were successfully treated in this study, 10 patients (43 percent) had significantly improved stroke symptoms 24 hours after the intervention. In the past, the consensus has been that if an artery is occluded 70 percent or more, there is benefit to opening it by surgery or, more recently, by stenting, Uchino said. But if it was completely blocked, the thought was that no interventions are possible to unblock the occluded vessel. Medical therapy was used instead. Most stroke neurologists believed that completely occluded arteries were blocked from the neck all the way into the skull, a condition called internal carotid artery (ICA) occlusion. ICA blockages were thought to be too big to be handled surgically by carotid endarterectomy or by stenting. Carotid endarterectomy is a procedure to surgically remove plaque from the carotid artery. When patients present early within hours of stroke symptoms or even within a few days with a fresh occlusion that occurred during acute stroke the lesions are actually shorter than we suspected. While some case reports have been published, this is the first study to report the outcome of stenting in these patients, he said. The patients, average age 62, were treated at the University of Pittsburgh Medical Center Stroke Institute between January 2002 and March 2005. Most of them (15) were referred for stenting because they had stroke symptom onset in the previous six hours and an imaging study documented ICA occlusion. Ten patients had fluctuating stroke symptoms such as difficulty speaking or paralysis on one side of the body and imaging evidence of inadequate blood flow to the brain because of an occluded ICA. Eight of the 25 patients had clot-busting therapy with tPA within hours before undergoing stenting without serious complication. In 2 patients, stenting attempts were unsuccessful. One patient underwent successful carotid endarterectomy surgery and the other was managed medically without aggressive intervention, Uchino said. The study is limited by being a retrospective analysis from a single institution. Still, Uchino said the findings suggest that the ideal candidate for carotid stenting of an occluded ICA is a patient who has a small area of irreversibly damaged brain tissue and a large area of at-risk, but salvageable, brain tissue. The principal investigator of the study was Tudor Jovin, MD, a stroke neurologist and neurointerventionalist at the University of Pittsburgh. Other co-authors are Rishi Gupta, MD, Charles A. Jungreis, MD, Lawrence R. Wechsler, MD, Maxim D. Hammer, MD, Ashis Tayal, MD and Michael B. Horowitz, MD. GE Healthcare Introduces AW RemoteAccess, Linking Clinicians to Advantage Workstation® Anywhere, Anytime GE Healthcare has introduced a software option that enables remote access to the capabilities of the Advantage Workstation®. New AW RemoteAccess software allows clinicians and physicians to apply AW functionality virtually anywhere, anytime via a PC or laptop computer. We expect AW RemoteAccess to make a significant contribution to our group’s workflow, and to improving our clinicians’ work lives, said Dr. Thomas Suby-Long, body imaging specialist of Diversified Radiology of Colorado. Instead of spending their time getting to an AW to review and evaluate patient studies, they will be able to interact with the images directly from their desktops or laptops or run the appropriate applications just as if they were sitting in front of the AW. This should add up to higher productivity, faster diagnostic results and happier physicians. AW RemoteAccess gives users a choice of two modes with which to access an AW. In Remote Review mode, multiple users can simultaneously access one host AW, performing interactive MIP/MPR (maximum intensity project/multiplanar reformat) tasks on any exam available at that AW, which customers have indicated are the most important day-to-day features for them. Clinicians may choose 3D review, multiplanar reformatting, real-time rotations, even ROI (region of interest), distance and angle measurements. Alternatively, a remote user can tap this software’s Virtual AW mode. In this mode, the user actually drives the host AW remotely, as if the user was actually sitting in front of the AW. The user can use any of AW’s specialty applications and features on any of the images in the AW database. Multiple users can be online to that AW at the same time, using it for Remote Review functions such as 3D image review. AW allows clinicians to visualize, analyze and share multimodality DICOM images, transforming data into decisions for patients in care areas like Cardiology, Oncology, Vascular Medicine, Orthopedics and Women’s Healthcare.

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