Selected News from Transcatheter Cardiovascular Interventions (TCT): October 12-17, 2008, Washington, D.C.

Medtronic: Danish Study, SORT OUT III, Looks at TLR, Stent Thrombosis for Endeavor® and Cypher® Stents

Medtronic, Inc. announced that the target lesion revascularization (TLR) rate for the company’s Endeavor® drug-eluting stent in the real-world Danish trial, SORT OUT III, was 4.0 percent. This result at nine months is consistent with the ENDEAVOR-Five real-world study, which reported an overall TLR of 4.5 percent at 12 months. The rates of myocardial infarction in the SORT OUT III study were very low for both the Endeavor (1.4 percent) and Cypher (0.5 percent) stents. The rate of stent thrombosis in SORT OUT III for Endeavor was 1.2 percent (ARC definition), consistent with typical rates of stent thrombosis for both drug-eluting and bare-metal stents after nine months of patient follow up. Surprisingly, however, the SORT-OUT III study at nine months reported a 1.0 percent TLR rate for Cypher — considerably less than the 4.5 percent TLR reported in the similar SORT OUT II study, Galloem et al, JAMA 2008, previously conducted in the same five centers by the same group. In addition, the stent thrombosis rate for the Cypher stent was 0.2 percent, compared to 1.7 percent reported in the SORT OUT II study. Dr. Jens Flensted Lassen, the study investigator, stated, “We were very surprised by these results — specifically those for Cypher and especially compared to the SORT OUT II data.” It was also noted during the presentation that late stent thrombosis becomes meaningful as a safety signal only after one year. Dr. Lassen commented on the safety outcomes in the study, which reported stent thrombosis for Endeavor of 1.2 percent at nine months: “This is only half the story, as we saw with ENDEAVOR IV, we expect late catch-up with Cypher.” Dr. Lassen’s comments acknowledge that while early events were also seen with Endeavor in the ENDEAVOR IV study at 12 months, there were no instances of late stent thrombosis with Endeavor after 369 days, in follow up to two years. Medtronic soon will complete enrollment in the PROTECT clinical study. The PROTECT study is the largest randomized trial focusing on the safety of drug-eluting stents. This 8,800-patient trial is being conducted at 200 centers worldwide and will compare Medtronic’s Endeavor stent and Cypher, made by Cordis, using key safety endpoints and other clinically relevant outcomes. The primary endpoint for the PROTECT study will be overall stent thrombosis at three years. ______________________________

New Data Shows Abbott’s Bioabsorbable Drug-Eluting Stent Is Absorbed Within Two Years, Leaving Behind Functioning Blood Vessels

Abbott announced two-year data from 30 patients in its ABSORB clinical trial, demonstrating that its bioabsorbable drug-eluting stent successfully treated coronary artery disease and was absorbed into the walls of treated arteries within two years, leaving behind blood vessels that appeared to move and function similar to unstented arteries. Patients who received Abbott’s bioabsorbable drug-eluting coronary stent and were followed out to two years experienced no stent thrombosis out to two years and no new major adverse cardiac events (MACE) between six months and two years. These results confirmed earlier positive one-year clinical results with Abbott’s bioabsorbable drug-eluting stent. The results were presented at the Cardiovascular Research Foundation’s 20th annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium. “Now you see it, now you don’t — for the first time, we have data in patients showing that Abbott’s bioabsorbable drug-eluting stent does its job treating diseased coronary arteries and that it is absorbed by two years,” said John Ormiston, MD, principal investigator in the ABSORB trial and medical director at Mercy Angiography in Auckland, New Zealand. “Clinical safety and effectiveness were sustained at two years, and the previously stented portion of arteries demonstrated the ability to expand and contract in a manner similar to a vessel that has never been stented.” Trends were observed in data from tests of artery movement and function, demonstrating a potential restoration of unstented artery movement to coronary blood vessels after the stent was absorbed. Abbott also presented intravascular ultrasound (IVUS) and optical computed tomography (OCT) imaging data on its bioabsorbable drug-eluting coronary stent platform at TCT in the “Best of Coronary Interventions Abstracts.” IVUS data revealed a decrease in plaque area in treated arteries corresponding to a similar increase in blood flow area between six months and two years: 12.7 percent decrease in plaque area (p≤0.001, n=17); 10.8 percent increase in luminal area (p=0.03, n=17). OCT imaging data showed absorption of the stent into artery walls and that the blood vessel lining of arteries treated with Abbott’s bioabsorbable stent looks more uniform after two years than it did immediately post-treatment. “The imaging technology data from the ABSORB trial indicate that Abbott’s bioabsorbable stent has the potential to restore vascular integrity and endothelial function to treated vessels after two years,” said Professor Patrick W. Serruys, MD, PhD, professor of interventional cardiology at the Thoraxcentre, Erasmus University Hospital, Rotterdam, and co-principal investigator in the ABSORB trial. “With these ABSORB data, we have come full circle in interventional time, linking the past, when balloon angioplasty was used without stents, to the future, when disappearing stents may become the new standard of care for patients with coronary artery disease.” Abbott is the only company with long-term clinical data evaluating the safety and performance of a fully bioabsorbable drug-eluting coronary stent out to two years. Abbott’s bioabsorbable everolimus-eluting coronary stent is made of polylactic acid, a biocompatible material commonly used in medical implants such as dissolvable sutures. Unlike a metallic stent, a bioabsorbable stent is designed to be slowly metabolized by the body and completely absorbed over time. Abbott will begin enrolling the next cohort of 80 patients into its international ABSORB clinical trial in the first half of 2009. Two-year data from the first 30 patients enrolled in the ABSORB clinical trial demonstrated a low (3.6 percent, n=28) MACE rate, which was consistent with results at one year (3.4 percent, n=29) and before six months (3.3 percent, n=30). One patient had a minor heart attack due to lack of blood supply at six months, another was electively lost to follow-up at one year, and one patient died from a non-cardiac cause at two years. A zero percent stent thrombosis rate persisted for all patients across all time points in the ABSORB trial. Potential restoration of unstented artery movement to coronary blood vessels after the bioabsorbable stent was absorbed was revealed at two years with the drugs acetylcholine and nitroglycerin used in nine patients, showing vasodilation in the previously stented area, and methergine used in seven patients, showing vasoconstriction in the previously stented area. The ABSORB trial is a prospective, non-randomized (open label) study designed to enroll up to 110 patients in Belgium, Denmark, France, New Zealand, Poland and the Netherlands. Key endpoints of the study include assessments of safety MACE (defined as any event that resulted in re-treatment of the treated artery, heart attack or cardiac death) and stent thrombosis rates at 30, 180 and 270 days, with additional annual follow-up for up to five years, as well as an assessment of the acute performance of the bioabsorbable drug-eluting stent. Other key endpoints of the study include successful deployment of the bioabsorbable drug-eluting stent, follow-up measurements assessed by angiography, intravascular ultrasound (IVUS), and state-of-the-art imaging modalities at 180 days and two years. For more information about the ABSORB trial, check out the June 2008 issue article, “Bioabsorbable Stents: “Patients want it, and it works,” an interview with John A. Ormiston, MB, ChB, principal investigator in the ABSORB trial, at https://cathlabdigest.com/article/8807 ______________________________

TAXUS OLYMPIA Registry: Outcomes For High-Risk Patients Treated With Second-Generation Taxus® Liberte® Stent

Boston Scientific Corporation announced positive one-year results from the Intercontinental and European launch phases of its global TAXUS OLYMPIA registry, the largest prospective, post-approval registry for a single drug-eluting stent (DES). OLYMPIA is designed to analyze real-world clinical outcomes data for Boston Scientific’s second-generation Taxus® Liberte® Paclitaxel-Eluting Coronary Stent System in the treatment of patients with coronary artery disease. Outcomes from the 22,000-patient study focused on high-risk lesion subgroups and patients with serious co-morbid conditions. Results were presented by Waqar H. Ahmed, MD, at the Cardiovascular Research Foundation’s (CRF) annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium in Washington, D.C. The TAXUS OLYMPIA registry employs a consecutive enrollment process and consists of diverse and high-risk patient populations, reflecting real-world patients found in everyday clinical practice. One-year data were collected for a total of 22,345 patients to date in 57 countries with cardiac events validated by independent medical review. A large majority of patients (75%) were considered “expanded use” cases consisting of challenging lesions or complex clinical characteristics. The overall OLYMPIA population included patients with multi-vessel disease (56.5%), prior PCI (27.9%), multiple stents (32.3%), and medically-treated diabetes (27.0%). One-year data demonstrated excellent outcomes for the Taxus Liberte Stent in patients with high-risk lesions (small vessels, long lesions, B2/C lesions) and patients with co-morbid conditions [prior stroke, acute myocardial infarction (MI), chronic renal disease]. Results demonstrated a low overall 4.4 percent rate of Taxus Liberte stent-related composite cardiac events, including cardiac death (1.4%), MI (0.9%), and re-intervention (TVR) (3.1%). The definite stent thrombosis rate was 0.8 percent after one year. The Taxus Liberte Stent also exhibited a high degree of procedural success at 99.7 percent. Dr. Ahmed, Armed Forces Hospital, Jeddah, Saudi Arabia, said, “The low occurrence of cardiac events and stent thrombosis is noteworthy, especially given the large percentage of high-risk patients and lesions from real-world practice in this study.” In the medically-treated diabetic subset of 5,692 patients, OLYMPIA reported a 5.1 percent rate of overall Taxus Liberte stent-related cardiac events, including cardiac death (2.3%), MI (1.1%), and re-intervention (TVR) (3.1%). Definite stent thrombosis was 0.8 percent, and remained low even in the insulin-treated diabetic patients at 1.0 percent. “This second-generation platform offers thinner struts and a stent geometry designed for more uniform drug elution,” said Donald S. Baim, MD, Chief Medical and Scientific Officer of Boston Scientific. The Taxus Liberte Stent has been approved by the U.S. Food and Drug Administration and is available for sale in the United States. The safety and effectiveness of the TAXUS Liberte stent have not been established in patients with multi-vessel disease, in-stent restenosis, AMI, multiple stents, lesions longer than 28 mm or arteries with an RVD less than 2.5 mm or greater than 4.0 mm. ______________________________

S.J. Park Given 2008 TCT Career Achievement Award Prize

Honors Pioneer In Interventional Vascular Medicine Seung-Jung Park, MD, PhD, FACC, world-renowned clinician, educator and researcher in the field of interventional vascular medicine, was presented the 2008 TCT Career Achievement Award in a ceremony held during the 20th annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium, sponsored by the Cardiovascular Research Foundation (CRF). The award recognizes Dr. Park as a pioneer in interventional vascular medicine, a leading authority on the implantation of stents in the left main heart artery, and as a dedicated and caring physician educator. Gregg W. Stone, MD, CRF Chairman, Professor of Medicine and the Director of Research and Education at the Center for Interventional Vascular Therapy at NewYork-Presbyterian Hospital/ Columbia University Medical Center, and Martin B. Leon, MD, Founder and Chairman Emeritus of CRF and Professor of Medicine and the Associate Director of the Center for Interventional Vascular Therapy at New York-Presbyterian Hospital/ Columbia University Medical Center jointly presented the award, which recognizes pioneering work in interventional medicine and extraordinary talent and dedication in both research and clinical endeavors. During the presentation, Dr. Stone noted that Dr. Park “is one of those rare individuals whose accomplishments have traveled beyond his local environment to have had a truly global impact. Over the last two decades he has methodically introduced the principles of evidence-based medicine to the Asia-Pacific region. He is the world’s most respected authority on left main stenting, the efficacy of which has been recently been borne out in a large randomized study. “His impact can also be seen in his roles as an educator, master clinician, researcher and as role model to his juniors and other interventionalists in Korea and throughout the Asian Pacific area.” According to Dr. Leon, “Dr. S.J. Park is an exciting choice for the TCT Career Achievement Award during our 20th Anniversary meeting. At a time when Asia-Pacific is emerging in world leadership roles in many segments of society, it’s fitting to honor Dr. Park, who is the premier interventional cardiovascular physician from this region.” Dr. Park’s long-time colleague, Gary S. Mintz, MD, Chief Medical Officer of CRF and himself a recognized expert on intravascular ultrasound, noted that, “Dr. Park put Korea on the map as far as interventional cardiovascular medicine is concerned. He showed his Korean colleagues that they had the intelligence, knowledge, and clinical competence to compete on the international stage. Ten years ago, no one knew of the Korean interventional community. Today it is common to pick up any journal and see a publication by one of the many Korean centers. He is an exceptional colleague and a great friend.” Dr. Park, who is Professor of Medicine and Chief of the Division of Interventional Cardiology of the Cardiovascular Center at Asan Medical Center, University of Ulsan, College of Medicine in Seoul, South Korea, said he has dedicated his career to “opening a new chapter of interventional cardiology, especially in the field of left main intervention.” His specific clinical interests include endothelial dysfunction and stenting in coronary artery disease — particularly in the left main artery of the heart. In addition to his position at Asan Medical Center, Dr. Park also currently serves as Director of the Clinical Research Center for Ischemic Heart Disease and as Director of Asan Heart Institute. ______________________________

Clinical Trial Results on Therapeutic Endovascular Cooling

Late-breaking results from the COOL RCN (COOLing to Prevent Radio Contrast Nephropathy in Patients Undergoing Diagnostic or Interventional Catheterization) Trial were presented during the 20th annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium, sponsored by the Cardiovascular Research Foundation (CRF). The prospective, randomized, multicenter clinical study was designed to evaluate the safety and effectiveness of catheter-based endovascular cooling for preventing in high-risk patients acute kidney failure. Acute kidney failure following exposure to intravascular contrast agents is known as radiocontrast nephropathy (RCN). Principal Investigator Gregg W. Stone, MD, CRF Chairman, Professor of Medicine and the Director of Research and Education at the Center for Interventional Vascular Therapy at NewYork-Presbyterian Hospital/Columbia University Medical Center, presented the findings of the study. Patients with pre-existing renal insufficiency, heart disease, or diabetes are at particularly high risk of developing RCN after cardiac catheterization. Mild hypothermia to protect the kidneys of high-risk patients while they are undergoing cardiac catheterization is one potential therapy. According to Dr. Stone, “This is a novel approach to preventing a common but serious side effect of radiographic contrast agents. The body is cooled from the inside out by approximately 7 degrees Fahrenheit.” The COOL RCN system enables the rapid induction of hypothermia in a conscious or unconscious patient by use of a venous heat exchange catheter. It provides very rapid, precise cooling, maintenance and re-warming of the patient’s core body temperature. A catheter is threaded into the femoral vein and positioned in the inferior vena cava. As cool sterile saline is circulated within the catheter, blood flowing past the catheter is cooled and, in turn, reduces body temperature. To re-warm the patient, the sterile saline within the catheter is simply warmed. In the COOL RCN trial, 136 patients were recruited between March 2006 and August 2007, and researchers were able to evaluate 128 patients. In the pilot study, 32 patients (median age 71, 50% diabetes) were hydrated and cooled to 33-34˚C less than 90 minutes prior to and for 3 hours after contrast was administered. Cooling had to be achieved before the first administration of contrast agent. The target core temperature in patients was 33˚C; no contrast was administered before 34˚C. The observed rate of RCN in the control arm — 18.6% — was lower than had been anticipated — 35%. This fact, coupled with the enrollment of only 136 of 400 planned patients (34%) resulted in a wide point estimate for the treatment effect of systemic hypothermia. Dr. Stone noted the trial was abbreviated due to a lack of funding. However, he concluded that based on the limited number of participants, “in patients at high risk for RCN undergoing invasive cardiology procedures, cooling may be safely achieved and is well-tolerated, but these results do not point to a significant reduction in RCN.” ______________________________

Endeavor Drug-Eluting Coronary Stent Linked to Fewer Heart Attacks at Two Years Post Implant

Latest Data from ENDEAVOR-IV Two-year results from the ENDEAVOR-IV clinical trial show that the Endeavor drug-eluting stent (DES) from Medtronic, Inc. is associated with statistically fewer heart attacks than Boston Scientific’s Taxus® DES. Dr. Martin B. Leon, founder and chairman emeritus of the Cardiovascular Research Foundation and principal investigator of ENDEAVOR-IV, presented the results at the Transcatheter Cardiovascular Therapeutics (TCT) meeting as part of a late-breaking clinical trials session. “Through two years of follow up in the ENDEAVOR-IV clinical trial, the Endeavor drug-eluting stent has proven to be statistically safer than TAXUS on the important measure of myocardial infarction, and no different in terms of efficacy as measured by the need for repeat procedures,” said Dr. Leon. “The latest data clarify the comparative safety and efficacy of these two drug-eluting stents beyond one year. As importantly, the data also show that Endeavor is associated with numerically fewer instances of very late stent thrombosis.” Referencing the long-term follow-up in the extensive ENDEAVOR clinical program, Dr. Leon added: “These safety and efficacy findings are remarkably consistent across the complete set of randomized trials, registries and pooled datasets that have featured the Endeavor stent.” In ENDEAVOR-IV, only one of the Endeavor patients (n=742) experienced a very late stent thrombosis (ARC definite/probable), compared to six of the TAXUS patients (n=739): 0.1 percent vs. 0.8 percent (p=0.069). Differences in duration of dual-antiplatelet therapy (DAPT) between the two groups underscore the safety benefits of the Endeavor stent. While a significantly greater proportion of patients randomized to the TAXUS stent received DAPT to two years of follow-up (p=0.02), the TAXUS patients experienced a 50 percent increased incidence of MI (p=0.02) and a seven-to-one higher ratio of VLST (p=0.06). Similarly to the VLST rates, the two-year follow-up on the primary endpoint of target vessel failure (TVF) — a composite of death, MI and target lesion revascularization (TLR) — favored Endeavor patients numerically compared to TAXUS patients: 11.1 percent (82/742) vs. 13.1 percent (97/739) (p=0.232), driven by a 34 percent reduction in cardiac death and MI to two years. ______________________________

SYNTAX Data Show Comparable Safety For Complex Patients Treated With Taxus® Express2™ Stents And Bypass Surgery

Boston Scientific Corporation announced 12-month left main and three-vessel disease subset data from its SYNTAX trial comparing percutaneous coronary intervention (PCI) using the Taxus® Express2™ Paclitaxel-Eluting Coronary Stent System to contemporary coronary artery bypass graft (CABG) surgery. The results reinforced previously announced data demonstrating no overall statistically significant differences between PCI and CABG in rates of death or myocardial infarction (MI). The Company also presented an analysis of the data based on the SYNTAX Score, a new tool that seeks to provide guidance to physicians on optimal treatment options for this high-risk group of patients, showing similar safety and efficacy outcomes for two-thirds of SYNTAX randomized patients. The SYNTAX trial is a large-scale randomized, controlled clinical trial comparing PCI using drug-eluting stents (DES) to CABG in patients with left main disease* and/or three-vessel** disease. The SYNTAX Score characterizes coronary anatomy based on lesion frequency, complexity and location, relying on data from the SYNTAX trial, and assigns a score to each patient. Analysis of the raw SYNTAX Score data demonstrated that PCI and CABG patients whose scores fell into the lower or intermediate terciles of complexity had similar rates of MACCE (major adverse cardiovascular or cerebrovascular event rate, including all-cause death, stroke, MI and repeat revascularization) at 12 months. For patients whose SYNTAX Score fell into the upper tercile — those with the greatest lesion complexity — there was a significant increase in MACCE for PCI patients compared with CABG patients. The average SYNTAX PCI patient received 4.6 stents, with one patient having 14. By contrast, the average number of stents implanted in a PCI patient in everyday practice is 1.5. In addition, the PCI patient profile includes 33 percent of patients with >100 mm stented length, 73 percent with bifurcations, 11 percent with trifurcations, 22 percent with chronic total occlusions, and 39 percent with left main disease. Some of the sickest patients in the trial were not eligible for surgery and were treated with DES. The SYNTAX trial enrolled 1,800 patients in its randomized arm, using a consecutive enrollment methodology. All patients were assessed by a multidisciplinary team including an interventional cardiologist and a cardiac surgeon. If both the cardiologist and surgeon felt they could offer equivalent complete revascularization, patients were randomized 1:1 into one of the two treatment methods (PCI or CABG). If either the cardiologist or surgeon felt that PCI or CABG was the preferred option, then patients were placed in one of two parallel registries for PCI or CABG. The Taxus Express² Stent System is contraindicated for use in patients with lesions involving a bifurcation/trifurcation, total occlusion of target vessel, unprotected left main coronary artery and lesions longer than 32mm. * isolated or in conjunction with 1-, 2-, 3-vessel disease ** revascularization for all 3 vascular territories ______________________________

FISH, First in a New Category of Biologic Vascular Closure Devices, Debuts at TCT ‘08

Next-Generation Patient Safety and Comfort; Advanced Biologic VCD Introduces Breakthrough Technology Morris Innovative introduced the FISH (Femoral Introducer Sheath & Hemostasis) vascular closure device at the Transcatheter Cardiovascular Therapeutics (TCT) in Washington, D.C. FISH is the first application of the clinically proven biomaterial SIS (small intestinal submucosa) for sealing arterial catheterization access sites. Infection-resistant SIS has long been used in various surgical applications and medical treatments. FISH is a biological closure device that prevents scar tissue, avoids inflammation and resists infection at the arteriotomy. “The FISH device is a novel and important advance in the development of vascular sealing devices,” said Kirk Parr, MD, The Care Group, St. Vincent’s Heart Center, Indianapolis, Indiana. Nine to 13 million diagnostic and interventional catheterizations are performed annually. All require a means of effective vascular closure to stop bleeding. FISH offers an alternative to staples or sutures that cause tissue reactions leading to scarring of the artery and difficulty with future reaccess. SIS-treated arteries regenerate, healing completely versus potential adverse and uncomfortable reactions as a result of encapsulating or absorbing foreign material used in other VCDs. In addition, the FISH device introduces technology that requires only a single sheath for both the introducer and vascular closure device. FISH is deployed in a way that compresses from inside the artery, to avoid nerve impingement and discomfort to the patient. FISH is the first in a new class of VCDs, designated as Closure Begins with Access (CBA) devices that introduce vascular closure at the beginning of the catheterization procedure. The FISH device is currently in limited product release in specific geographic regions, with plans for a full U.S. launch in early 2009. ______________________________

Abbott’s Xience V™ Drug-Eluting Stent Outperforms Taxus® in Key Efficacy and Safety Endpoints Out to Two Years

Data from an independent meta-analysis of Abbott’s SPIRIT II and SPIRIT III randomized clinical trials demonstrated that the Xience V™ Everolimus Eluting Coronary Stent System continues to deliver clinically significant benefits for patients compared to the Taxus® paclitaxel-eluting coronary stent system out to two years. In this meta-analysis, which included patients from the United States, Europe and Asia-Pacific, Xience V demonstrated clinical superiority to Taxus in the endpoints of target vessel failure (TVF) and major adverse cardiac events (MACE) at two years. Xience V also demonstrated significantly lower clinical events rates than Taxus in the key efficacy (target lesion revascularization) and safety (cardiac death or heart attack) components of MACE at two years. The results were presented by Gregg W. Stone, MD, principal investigator of the SPIRIT III trial, during the Cardiovascular Research Foundation’s 20th annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium. Dr. Stone, professor of medicine at Columbia University Medical Center and chairman, Cardiovascular Research Foundation, New York, said, “In the meta-analysis at two years, Xience V compared to Taxus demonstrated statistically significant reductions in the combined measure of all-cause death or heart attack, as well as further reducing the need for repeat cardiac procedures.” The meta-analysis of 1,302 patients from the SPIRIT II and SPIRIT III trials demonstrated the following key results for Xience V at two years: • A clinically significant 31% reduction in the risk of ischemia-driven target vessel failure compared to Taxus (10.4% for Xience V vs. 14.7% for Taxus, p-value=0.03)*. • A clinically significant 45% reduction in the risk of ischemia-driven MACE compared to Taxus (7.1% for Xience V vs. 12.3% for Taxus, p-value=0.001)*. • An observed 28% reduction in the risk of all-cause death compared to Taxus (2.4% for Xience V vs. 3.3% for Taxus, p-value=0.36)*. • An observed 28% reduction in the risk of cardiac death compared to Taxus (0.9% for Xience V vs. 1.3% for Taxus, p-value=0.56)*. • A clinically significant 45% reduction in the risk of MI compared to Taxus (3.1% for Xience V vs. 5.6% for Taxus, p-value=0.03)*. • A clinically significant 39% reduction in the risk of all-cause death or MI compared to Taxus (5.1% for Xience V vs. 8.3% for Taxus, p-value=0.03)*. • A clinically significant 41% reduction in the risk of cardiac death or MI compared to Taxus (3.8% for Xience V vs. 6.3% for Taxus, p-value=0.04)*. • A clinically significant 41% reduction in the risk of ischemia-driven target lesion revascularization compared to Taxus (4.1% for Xience V vs. 6.8% for Taxus, p-value=0.03)*. *Event rates are based on Kaplan-Meier estimates; p-values are for descriptive purposes only. • Low rates of stent thrombosis between one and two years, defined as very late stent thrombosis, per Academic Research Consortium (ARC) definition of definite/probable stent thrombosis (0.5% for Xience V and 0.8% for Taxus). Xience V is built upon Abbott’s bare-metal stent, the Multi-Link Vision® Coronary Stent System. Abbott also supplies a private-label version of Xience V to Boston Scientific called the Promus™ Everolimus-Eluting Coronary Stent System. Promus is designed and manufactured by Abbott and supplied to Boston Scientific as part of a distribution agreement between the two companies. Additional information about Xience V is available online at www.xiencev.com. ______________________________

Volcano Corporation Announces Launch of PrimeWire™ Pressure Guidewire and s5-FFR Option for Existing Fleet of s5 IVUS Consoles

FAME Data Demonstrates 30% Reduction in Composite Events When Using Routine FFR Guidance in Multi-Vessel Disease Volcano Corporation announced the launch of the PrimeWire™ Pressure Guidewire, and the s5-FFR Option for its existing installed base of s5 and s5i imaging consoles in the U.S. The PrimeWire is Volcano’s newest pressure guidewire, capable of measuring pressure gradients across a lesion to determine the ischemic nature of the stenosis, and can also help determine the extent to which the blockage is flow-limiting. The s5-FFR Option is now available for existing s5 and s5i consoles currently installed throughout the U.S. and Europe to enable these IVUS consoles with FFR (fractional flow reserve) technology. Volcano continues to be the only company offering an imaging console capable of high-frequency rotational IVUS, fast digital IVUS and FFR. The one-year follow up of the FAME study (FFR vs. Angiography for Multivessel Evaluation) was presented at TCT and confirms the beneficial clinical and economic impact of FFR when used routinely to guide treatments of multi-vessel disease. “The FAME study is among the most important studies in today’s DES therapy era. FAME demonstrates that when physicians employ FFR to guide multi-vessel PCI treatment, their patients benefit both clinically and economically. The FFR-guided interventions for multi-vessel disease are also cost effective for hospitals and payers. FAME confirms the benefits of routine FFR for the multi-vessel patient just as the earlier Deferral versus Performance of PTCA in Patients Without Documented ischemia (DEFER) study demonstrated in single-vessel disease, but does so in a larger patient population and in a randomized fashion,” commented Morton Kern, MD, professor of medicine and associate chief, Division of Cardiology, University of California, Irvine. FAME randomized 1,005 patients diagnosed with multi-vessel coronary artery disease at 20 European and U.S. centers to either angiography-guided PCI (n=496) or FFR-guided PCI (n=509) all using current DES regimens. FAME’s objective was to compare angiographic guidance to FFR guidance and to determine which coronary lesions required revascularization. The study demonstrated that FFR guidance in routine multi-vessel PCI resulted in clinically superior outcomes and reduced the composite of death, documented myocardial infarction, and repeat revascularization by 30 percent at one year. It also demonstrated that adhering to an FFR-guided regimen for multi-vessel disease is cost beneficial to the hospital and payers by reducing procedural costs ($5,332 vs. $6,007), lowering average length of hospitalization (3.4 days vs. 3.7 days) and reducing the number of drug-eluting stents necessary per patient (1.9 vs. 2.7). The data also showed that the implementation of FFR did not add time to the multi-vessel PCI procedure. DEFER is a landmark study demonstrating that patients with intermediate disease not treated with PCI based on FFR guidance achieved long-term outcomes out to five years equivalent to patients who underwent PCI for similar intermediate lesions. DEFER outlines a revascularization strategy for angiographically equivocal stenoses that deploys FFR technology to identify and treat only those lesions producing reversible ischemia. The Journal of the American College of Cardiology has recognized the five-year follow-up results of the DEFER trial as one of the studies with the greatest impact on clinical cardiology in 2007 (JACC 2008;51:490-512). The PrimeWire was showcased at TCT in two live case demonstrations performed at Columbia Presbyterian Medical Center in New York and at Riverside Medical Center in Columbus, Ohio. As a pressure wire, the PrimeWire measures intracoronary pressure to derive an FFR index. FFR expresses maximum achievable blood flow in a coronary artery with the presence of an abnormal stenosis as a fraction of maximum blood flow achievable in the absence of a stenosis. FFR is 100% specific in identifying lesions actually restricting blood flow enough to cause ischemia. Joe Burnett, Associate Vice President, marketing, commented, “Earlier-generation consoles included only one of the three technologies now available on the s5. If a hospital wanted to equip a new lab with all three technologies, they would have to acquire three separate consoles, each with a different measurement modality, training requirements and data storage protocols. The Volcano s5 can now accommodate the three primary intravascular diagnostic tools in regular use by cardiologists today (high frequency rotational IVUS, fast and simple digital IVUS, and pressure-based FFR guidewires) on a single platform, making modern day imaging consoles more flexible than ever before.” ______________________________

Bivalirudin Reduced Cardiac Mortality by 43 Percent and Improved Overall Survival by 31 Percent in HORIZONS-AMI Trial

First Trial of Pharmacologic Therapy to Demonstrate a Mortality Benefit in STEMI Patients Undergoing Primary PCI The Medicines Company announced one-year follow-up data from the landmark HORIZONS-AMI trial demonstrated that bivalirudin (Angiomax®) significantly reduced cardiac-related death by 43 percent (p=0.005), improved overall survival by 31 percent (p=0.029) and reduced major bleeding complications by 39 percent (p

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