Clinical and Industry News for December 2007

Clinical Study Shows 50% Reduction in Median Time-to-Hemostasis for Vascular Solutions’ D-Stat Dry Hemostatic Bandage Vascular Solutions, Inc. announced the published results of a 376-patient, five-center, prospective randomized U.S. clinical study regarding its thrombin-based D-Stat Dry hemostatic bandage used for the control of surface bleeding from vascular access sites following percutaneous procedures. The study showed that when used as an adjunct to hemostasis, D-Stat Dry reduces time to hemostasis following diagnostic femoral catheterizations using 4F-6F introducer sheaths, compared with standard manual compression alone. A 50-percent reduction in median time-to-hemostasis (6 minutes with D-Stat Dry vs. 12 minutes with manual compression alone) was observed. The randomized 1:1 D-Stat Dry to manual compression study also demonstrated a lower rate of adverse events (0.5% with D-Stat Dry vs. 1.1% with manual compression alone). The results of the study, The Use of the D-Stat Dry Bandage for the Control of Vascular Access Site Bleeding: A Multicenter Experience in 376 Patients, were published in the July/August 2007 issue of Cardiovascular & Interventional Radiology. Five sites participated in the study: Charleston Area Medical Center, Charleston, WV; Abbott Northwestern, Minneapolis, MN; Tri-Health (Good Samaritan/Bethesda), Cincinnati, OH; Mount Sinai Medical Center, Miami, FL; and Terrebonne General Medical Center, Houma, LA. Certain Infusion Therapy After STEMI Does Not Appear to Be Beneficial, May Cause Harm Infusion of a combination therapy consisting of glucose, insulin, and potassium, which was thought could be a beneficial treatment immediately following a heart attack, may increase the risk of heart failure and death in the first 3 days for patients with ST-segment elevation myocardial infarction (STEMI), according to a study in the Journal of the American Medical Association. Small studies have supported the use of glucose-insulin-potassium (GIK) infusion in the treatment of STEMI, while a larger study indicated a neutral effect of GIK infusion on the risk of death at 30 days after a heart attack. Rafael Díaz, MD, of the Etudios Cardiologica Latin America, Rosario, Argentina, and Abhinav Goyal, MD, MHS, from the Emory School of Medicine, Atlanta, and colleagues conducted a study to determine the association between GIK infusion therapy and 30-day and 6-month outcomes in patients with STEMI, and whether GIK infusion may cause harm in the early post-infusion period. The study included analysis of the outcomes of the OASIS-6 GIK randomized controlled trial of 2,748 patients with acute STEMI, and the prespecified analyses of the combined trial data from the OASIS-6 GIK and CREATE-ECLA GIK trial populations of 22,943 patients with acute STEMI. The researchers found that in the OASIS-6 trial, there were no differences between the GIK infusion and control groups in the 30-day outcomes of death, heart failure, or the composite of death or heart failure. There also were no differences in six-month clinical event rates. In the combined OASIS-6 and CREATE-ECLA GIK trial results, there were no differences between the GIK infusion and control groups in the 30-day rate of death, heart failure, or the composite of death or heart failure. In the analyses from days 0 to 3, the risks of death and the composite of death or heart failure were higher in the GIK group compared with the control group, with 712 deaths (6.2 percent) in the GIK group and 632 deaths (5.5 percent) in the control group; and 1,509 death or heart failure events in GIK group (15.8 percent) and 1,388 events in the control group (14.5 percent). The difference in the death rate disappeared by 30 days, with 1,108 deaths (9.7 percent) in the GIK group and 1,068 (9.3 percent) in the control group. GIK therapy increased levels of glucose, potassium, and net fluid gain post-infusion, all three of which predicted death after adjusting for multiple confounders. Adjusting for glucose, potassium, and net fluid gain eliminated the apparent increase in mortality at 3 days observed with GIK infusion, suggesting a direct association with these factors. Administration of GIK infusion within 4 hours of symptom onset yielded no benefit compared with later initiation, the authors write. The combined OASIS-6 and CREATE-ECLA trial analysis of almost 23,000 patients with STEMI (the largest global experience with GIK therapy) demonstrates that GIK infusion has no effect on any important clinical end point through 30 days following STEMI. However, contrary to our prespecified hypothesis, we observed a higher rate of death and the composite of death or heart failure at 3 days in patients allocated to GIK therapy compared with control. Source: JAMA 2007;298(20):2399-2405. COURAGE Sub-study: PCI Outperforms Drugs-Only Patients with ischemia benefit significantly from percutaneous coronary intervention (PCI) when compared with optimal medical therapy, according to a nuclear sub-study of the COURAGE trial presented at the American Heart Association (AHA) in Orlando. This sub-study is especially significant given that the COURAGE trial had previously called into question the relative effectiveness of PCI compared to medications alone in the prevention of death and heart attack in patients with stable heart disease. The Society for Cardiovascular Angiography and Interventions (SCAI) questioned those findings from the beginning. SCAI noted that the COURAGE study excluded all but the most stable patients, including only those who were able to adhere to very strict medication and lifestyle-change requirements. COURAGE also enrolled patients only after their anatomy was determined, another significant study design limitation. Furthermore, the existing data had never suggested that angioplasty or stenting reduced the risk of death or heart attack in this population of stable patients. This new analysis confirms what interventional cardiologists have said all along when compared to using only drugs, PCI improves overall heart health and reduces debilitating chest pain by opening up blocked arteries, said Dr. Bonnie Weiner, President of The Society for Cardiovascular Angiography and Interventions. Patients with stable coronary artery disease, especially those with a moderate to severe case, gained significant long-term health benefits from PCI when compared with a drugs-only approach, according to Dr. Leslee J. Shaw, the principal investigator and a professor of medicine at Emory University, who presented the late-breaking clinical trial at the AHA Scientific Sessions. Using a nuclear imaging technique called single photon emission computed tomography (SPECT), the study showed that patients with moderate to severe ischemia benefited most from PCI when compared with those who received only optimal medical therapy. In fact, when ischemia was reduced, the risk of death was also reduced. This finding confirms cardiologists’ general understanding of heart disease that significant ischemia is not in a patient’s best long-term interests. The SPECT images, which enable physicians to assess the blood flow to the heart, showed that some patients had a very significant reduction in ischemia (more than 5 percent). Of patients who underwent PCI and took medications, 33 percent showed a reduction in ischemia of 5 percent or more, compared with only 19 percent of patients who took only medications. This study also confirms the importance of identifying patients who are at most risk and who can therefore most benefit from PCI," Dr. Weiner said. Among the patients who had reduced ischemia, nearly 80 percent of both treatment groups were free of angina, which is characterized by chest pain that can be debilitating. PCI in addition to medications is clearly more effective than a medications-only approach in patients with high-risk ischemia (those with greater than 5 percent of their heart muscle compromised), according to the study. The COURAGE trial received widespread attention earlier this year when some concluded that PCI offered no reduction in the risk of death or heart attack in patients with stable coronary artery disease compared with using only drugs. The overall COURAGE trial looked at a narrow group of relatively healthy, stable patients who represented only about 30 percent of patients treated by interventional cardiologists. The nuclear sub-study demonstrates that even in these patients, the continued presence of ischemia increases the risks of death or heart attack. These risks can be reduced with revascularization. The COURAGE trial did not consider that many patients are not suitable for a medications-only approach because, although that approach may be desirable and recommended, such patients may not be able to tolerate side effects of the drugs or adhere to the strict regimen required due to multiple factors. The COURAGE trial also did not address significant quality-of-life factors for the stable angina population. In consultation with their physicians, many patients choose PCI because it offers almost immediate relief from pain and discomfort, and they are much more likely to be able to resume normal lifestyle activities sooner with far fewer symptoms than many patients who choose the medications-only route. If you are interested in reading more about the presentation of this nuclear sub-study, please visit: https://scientificsessions.americanheart.org/portal/scientificsessions/ss/lbctnr2a.2007 Abiomed Announces Results of Impella® 2.5 FDA PROTECT I Safety Trial for High-Risk PCI Cases Abiomed, Inc. announced the results of its Impella® 2.5 PROTECT I safety trial for the first time at the Cardiovascular Research Foundation’s (CRF) annual Transcatheter Cardiovascular Therapeutics (TCT) Scientific Symposium and main sessions. PROTECT I is the first prospective multi-center, FDA-approved trial for prophylactic, or preventative, use of a device during high-risk percutaneous coronary intervention (PCI) procedures. The 20-patient pilot study with the Impella 2.5 met all primary and secondary endpoints and showed very low adverse event rates in a very sick patient population. The results demonstrated no incidents of: aortic valve damage, aortic or mitral dysfunction, sepsis, stroke, thromboembolic events, vascular complications, insertion-site infection, device malfunction, device-related bleeding, limb ischemia, or clinical issues with hemolysis. "We begin the pivotal study with an expanded patient population, including high-risk PCI with triple-vessel disease for patients at up to 150 centers, said Michael R. Minogue, Chairman, CEO and President of Abiomed. Experience with the Impella 2.5 in the safety trial and in multiple studies in Europe under CE-Mark provides significant evidence of the clinical benefit to patients, and we continue to work with the FDA to bring this technology to the U.S." "In the PROTECT I pilot trial, Impella delivered supreme protection and support. It enabled success in procedures that would have been otherwise impossible," said Dr. J.P.S. Henriques, Cardiologist at the Academic Medical Center in Amsterdam. Dr. Laura Mauri of Brigham & Women’s Hospital also presented new data from the completed PROTECT I trial: "Feasibility Trial Investigating the Use of the Impella 2.5 System in Patients Undergoing High-Risk PCI." An independent core lab analysis completed at Duke University determined no damage to the septum, heart chambers, or mitral/aortic valves. At a 30-day follow-up, patients enrolled in the PROTECT I trial showed an improvement of their heart function demonstrated by an absolute increase of 7% in their left ventricular ejection fraction, equating to a 27% relative increase. "We have been impressed by the ease-of-use and high safety profile of the Impella 2.5 technology during the PROTECT I pilot trial, said Dr. William O’Neill, National Principal Investigator for the pilot and pivotal studies of the Impella 2.5, and Professor and Executive Dean for Clinical Affairs, Division of Cardiology at the Leonard M. Miller School of Medicine at the University of Miami. Also announced for the first time at TCT was Abiomed’s new percutaneous right side catheter that can deliver greater than 4 liters of flow. This product will provide key support to the failing right ventricle and will be introduced first in Europe. Visit www.abiomed.co m for more information. Computed Tomography Angiography Accurate in Detecting Coronary Artery Disease Computed tomography (CT) angiography is as accurate as an invasive angiogram in detecting coronary artery disease, according to the findings of the first two prospective multi-center 64-slice scanner trials presented at the annual meeting of the Radiological Society of North America (RSNA). These two trials with comparable results clearly set the stage for the widespread adoption of and reimbursement for coronary artery CT examinations, said Gerald D. Dodd III, MD, chair of the Department of Radiology at the University of Texas Health Science Center in San Antonio. For the Coronary Artery Evaluation Using 64-Row Multidetector Computed Tomography Angiography (CORE-64) Trial, researchers at nine international centers studied 291 patients who were scheduled to undergo invasive coronary angiography for suspected or unknown coronary artery disease. The study found that 64-slice multidetector CT angiography was highly accurate in detecting blockages of greater than 50 percent, with a sensitivity of 85 percent and a specificity of 90 percent. The noninvasive exam was equal in accuracy to invasive angiography in its ability to identify patients to be referred for angioplasty or bypass surgery. Reliable assessment of the presence of coronary blockages and accurate prediction of coronary revascularizations are feasible with 64-slice CT coronary angiography, said presenter Marc Dewey, MD, radiologist at Humboldt University Berlin, Charite, Germany. Patients with low to intermediate risk of having coronary blockages are most likely to benefit from coronary CT angiography, since in those patients the necessity of invasive angiography is greatly reduced. The Assessment by Coronary Computed Tomographic Angiography of Individuals UndeRgoing InvAsive Coronary AngiographY (ACCURACY) Trial compared 64-row coronary computed tomographic angiography (CCTA) to quantitative coronary angiography (QCA). The results demonstrated that CCTA is highly accurate in detecting coronary blockages in chest pain patients referred for invasive coronary angiography and is also an effective noninvasive method to exclude obstructive coronary blockages. Sixteen institutions performed CCTA on 232 patients with typical or atypical chest pain prior to invasive coronary angiography. Findings were then compared to those of QCA, the reference standard used to quantify the results of the invasive coronary angiography. A total of 82 blockages greater than 50 percent in 49 patients and 31 blockages greater than 70 percent were detected in 28 patients by QCA. Per-patient sensitivity and specificity of CCTA were 93 percent and 82 percent, respectively, for blockages greater than 50 percent, and 91 percent and 84 percent for blockages greater than 70 percent. In addition, negative predictive value was 97 to 99 percent. In a population of chest pain patients with a low to intermediate prevalence of obstructive coronary artery blockages, CCTA performed highly accurately compared to invasive coronary angiography, said presenter James K. Min, MD, assistant professor of radiology and medicine at New York Presbyterian Hospital and director of the Cardiac Computed Tomography Laboratory and Cornell University Medical Center. Comprehensive Safety and Efficacy Data on Xience V Drug-Eluting Stent Presented by Abbott to FDA Advisory Committee on Nov. 29 New Data Released Confirms Consistency of Results for Late Loss, TVF, MACE, TLR, Cardiac Death, MI, Thrombosis Across all Xience V Studies Abbott released a summary of clinical highlights on the Xience V Everolimus Eluting Coronary Stent System, presented Nov. 29 to the Circulatory System Devices Advisory Panel, an advisory committee to the U.S. Food and Drug Administration (FDA). The clinical summary was released in conjunction with the posting of the Panel briefing documents on the FDA web site (https://www.fda.gov). The advisory panel will review the data and recommend if the FDA should approve Xience V, a next-generation drug eluting stent for the treatment of coronary artery disease. Data made available as part of the Panel documents include two-year safety results from a pooled subset of 603 patients from the SPIRIT II and SPIRIT III trials (422 treated with XIENCE V). Results from this subset are consistent with the positive SPIRIT III one-year data and the pooled analysis of the SPIRIT II and SPIRIT III trials at one year presented at TCT 2007. The new two-year subset data analysis shows similar low rates of major adverse cardiac events (MACE), target vessel failure (TVF), cardiac death, heart attack, and stent thrombosis as previously reported in the SPIRIT trials. The pooled two-year subset data also show similar rates of death, myocardial infarction (MI), and late stent thrombosis (31-758 days) between Xience V and the Taxus® Paclitaxel-Eluting Coronary Stent System at two years. Across all of the SPIRIT trials, XIENCE V has met its primary and major secondary endpoints, demonstrating either noninferiority or clinical superiority compared to TAXUS, the most widely used drug eluting stent, said Gregg W. Stone, MD, of Columbia University Medical Center and the Cardiovascular Research Foundation, New York, principal investigator of the SPIRIT III clinical trial. The data out to two years also demonstrate XIENCE V is safe, with low rates of death, heart attack and stent thrombosis, which were comparable to TAXUS, with improved efficacy in terms of freedom from clinical restenosis. Abbott’s continued access and post-approval program is projected to enroll more than 14,000 Xience V patients across a variety of planned clinical trials. Abbott also outlined plans for its XIENCE V USA trial, a 5,000 patient post-approval trial designed to study safety outcomes such as late stent thrombosis, death, MI and revascularization with follow-up out to five years. The study also will evaluate patient compliance with antiplatelet therapy. In addition to XIENCE V USA, SPIRIT IV is a 3,690-patient continued access trial that is currently enrolling patients and will evaluate the safety and efficacy of Xience V for the treatment of coronary artery disease in a more complex patient population in the United States. SPIRIT V is an international clinical trial that will provide additional clinical experience with Xience V in approximately 3,000 patients at approximately 100 clinical sites throughout Europe, Asia, Canada and Latin America. XIENCE V SPIRIT WOMEN is the world’s first drug-eluting stent trial to study only women and will evaluate the characteristics of 2,000 women undergoing stent implantation as well as the performance of Xience V in those patients in Europe, Asia-Pacific, Canada and Latin America. Both SPIRIT V and XIENCE V SPIRIT WOMEN are currently enrolling patients. Abbott filed its Premarket Approval (PMA) submission for Xience V with the FDA on June 1, 2007. Xience V was launched in Europe and other international markets in 2006. Xience V is currently an investigational device in the United States and Japan. Barry T. Katzen, MD, honored with Career Achievement Award Barry T. Katzen, MD, founder and course director of the International Symposium on Endovascular Therapy (ISET, January 20-24, 2008, www.iset.org), received the prestigious Career Achievement Award of the 2007 Transcatheter Therapeutics Conference (TCT) in Washington, D.C. An interventional radiologist, Dr. Katzen, 61, was honored for his pioneering development of angioplasty for vessels outside the heart. Dr. Katzen performed the first peripheral angioplasty in the United States in 1978 by using a balloon mounted on a catheter to open a blocked artery. Dr. Katzen is the founder and medical director of Baptist Cardiac & Vascular Institute in Miami, Florida. He graduated from the University of Miami School of Medicine and completed his residency at the New York Hospital-Cornell Medical Center.

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