CMO Newsletter Q4 2009

Dear Colleagues,

As we embark on a New Year, I would like to take a moment to reflect on 2009, a remarkable year for Abbott Vascular. I would like to share with you some of the progress we have made and our plans for the future across coronary and peripheral interventions and structural heart disease therapies. These are just a few of the key highlights in this newsletter that I hope you will find useful to your practice. 

Regards, 

Chuck Simonton, MD

Chief Medical Officer and

Divisional Vice President, Medical Science Group

Abbott Vascular

Reflections on 2009

Highlights From Abbott Vascular

Ü    SPIRIT V “Real-World” Registry: Data Shows an Observed Low MACE Rate for XIENCE V at One Year

The first real-world registry of XIENCE V – SPIRIT V (initiated following the CE mark {Conformité Européenne} for XIENCE V in Europe) - reached its one-year follow-up with data presented at EuroPCR 2009 in Barcelona, Spain. The registry showed MACE defined as Target Lesion Failure (TLF) (cardiac death, target vessel MI, and TLR) of 5.1% and a TLR of 1.3%. In addition, a 0.66% stent thrombosis rate (ARC definite + probable) was observed at one year in a complex population. As 2009 progressed, with the roll out of more closely monitored studies such as SPIRIT IV and COMPARE, SPIRIT V data were observed to be in parity on efficacy and safety measures.

Ü    Cross-Industry DAPT Trial’s First Patient Randomized to XIENCE V

After 18 months of planning the study and negotiating with the FDA, four prominent DES companies and two pharmaceutical companies, in collaboration with the Harvard Clinical Research Institute, launched an FDA-mandated study to determine if DES patients can safely discontinue their dual antiplatelet therapies at 12 months post-procedure without the added risk of MACE or stent thrombosis. Since Abbott Vascular was the only DES manufacturer to have a large registry of patients reaching its one-year anniversary (XIENCE V USA Post-Market Study), we were able to jump-start the DAPT study, obtaining more immediate informed consents of participating patients to enroll and be randomized to a thienopyridine vs. placebo. Indeed, the first patient for the FDA DAPT Trial was enrolled on Oct. 5, 2009 and was randomized to continued DAPT vs. placebo. Abbott Vascular is fully committed to this landmark DES safety study, which will randomize patients to 12 vs. 30 months of DAPT in a large, randomized, well-controlled, placebo vs. drug study design.

The EXCEL Left Main Trial for XIENCE PRIME vs. CABG is Announced

As the XIENCE V everolimus-eluting stent platform sustains its market-leading share in the U.S. and around the world, has become incumbent upon Abbott Vascular to consider the next key strategic clinical trial for DES. Many different trials were considered – the one that the vast majority of clinicians recommended was a prospective randomized trial comparing the XIENCE PRIME stent*, only available in Europe, to coronary artery bypass surgery for unprotected left main disease, including patients with one-, two- or three-vessel disease; thus, the birth of EXCEL (Evaluation of XIENCE PRIME vs. Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization). The trial plan was announced by Dr. Gregg W. Stone during TCT 2009. Dr. Stone, together with Drs. Patrick W. Serruys, Joseph Sabik and Pieter Kappetein, will represent cardiology and surgery as the global principal investigators for the trial. Much deliberation between interventionalists and surgeons has led to the final trial design, which will have a primary endpoint of death, MI, or stroke at a median of three-year follow-up in 2,500 patients. The major secondary endpoint will be the composite of death, MI, stroke, or TVR. EXCEL is expected to launch enrollment in 2010.

*Caution:  Investigational Device. Limited by Federal (or United States) law to investigational use. Not available for use or sale in the U.S.

Ü    SPIRIT II Randomized Trial (OUS) at Three Years of Follow-Up Shows 57% Reduction in MACE Compared to TAXUS with a Three-Year Rate of Only 6.4% (p=0.029)

The first three-year clinical data for XIENCE V from a randomized trial against TAXUS was SPIRIT II, the prospective RCT in 300 patients in Europe which had previously shown superiority of angiographic late loss for XIENCE V at six months. The three-year data were presented at ACCi2 2009, revealing a low three-year MACE rate of 6.4%. These data had not been shown for a DES in a prospective randomized trial before. In addition, ID-TLR was 4.2% and the stent thrombosis rate (ARC) was a low 0.9% for the entire three-year period (with ZERO in the first year). Compared to TAXUS, all rates were lower. Both TAXUS Express (73% of lesions) and TAXUS Liberté (27% of lesions) were used as controls in SPIRIT II.

Ü   Abbott Vascular’s Endovascular Business Had Quite a Busy Year … Key Highlights Included:

•   Completion of the multicenter HERCULES Trial* (enrollment completed; follow-up ongoing)

•   Completion of the multicenter XCELL Trial* (enrollment completed; follow-up ongoing)

•   Worldwide launch of Emboshield NAV⁶ Embolic Protection Filter*

•   Completion of the multicenter DESTINY Trial* (enrollment completed; follow-up ongoing)

•   Initiation of a multicenter randomized trial to further study Prostar and ProGlide in femoral punctures

•   Launch of the Omnilink Elite .035 Balloon Expanding Stent* outside the U.S.

*The safety and effectiveness of this device for use in the vascular system have not been established. Not available for sale in the U.S.

Ü   BIORESORBABLE VASCULAR SOLUTIONS (BVS) COHORT B

Leveraging data showing enlarging lumens and return of vascular function at two years, with no MACE or stent thrombosis after six months, the COHORT B study launched enrollment in 2009. Based on a new bioresorbable scaffold design featuring a MULTI-LINK pattern with radial strength similar to XIENCE V, and designed to be as deliverable, the COHORT B fully bioresorbable polylactic acid scaffold was placed in 101 patients. The first six-month angiographic, IVUS and OCT images in an initial group of 10 patients, at the time of this writing, indicate an observed preservation of scaffold dimensions and low late loss. There was no scaffold thrombosis reported to date, which is encouraging and in line with hopes of designing a safe platform. So, BVS marches ahead, leading the future for fully resorbables scaffolds. The clinical program will accelerate in 2010.

Ü  Evalve is Acquired: New Company to the Abbott Family Introduces Structural Heart Disease Therapy Into the Abbott Vascular Portfolio

Abbott Vascular has been following the field of percutaneous mitral valve repair for many years, in particular through its investment in Evalve. Last year, Abbott Vascular acquired Evalve in November 2009. The company has completed EVEREST II, a prospective randomized clinical trial comparing a percutaneous option to mitral valve surgery in patients with mitral regurgitation.  

Ü  PROSPECT Trial for Vulnerable Plaque

The PROSPECT trial reached three years of follow-up, and these results were presented at TCT 2009. Of interest, IVUS lesion characteristics predicted that a particular lesion correlates to adverse cardiac clinical events, particularly an IVUS plaque burden ≥70% or presence of Thin-Capped Fibroatheromas (TCFAs). If a lesion showed both of these, the incidence of MACE at three years was 15.3%, a significant correlation to this combination. PROSPECT has opened the door to potential vulnerable plaque interventions in the future, balancing the risk of an added intervention (perhaps with an additional stent) against the risk of a cardiac event if the lesion is left untreated. 

Ü  SPIRIT III Randomized Trial (U.S.) at Three-Year Follow-Up Shows Significant 43% Reduction in MACE (p=0.003) With a SINGLE DIGIT Three-Year Rate of 9.1%, and Lower Very Late Stent Thrombosis Compared to TAXUS Express

The most significant body of long-term follow-up data for the XIENCE V stent comes from SPIRIT III, the pivotal U.S. randomized trial comparing XIENCE V to TAXUS EXPRESS in more than 1,000 patients. The three-year results, presented at TCT 2009, showed a single-digit MACE rate of only 9.1% in a study that allowed for two vessels to be treated; the study included a large mandated angiographic subgroup that always naturally increase rates of TLR for any device. The three-year TLR rate was 5.4% with a stent thrombosis rate (ARC definite + probable) of only 0.3% after one year. (Zero new stent thrombosis and stent thrombosis cases for XIENCE V between year-2 to year-3) 

Ü  SPIRIT IV Randomized Trial (Largest DES Trial to Date) Shows One-Year TLF (4.2% vs. 6.8%, p=0.001) and ID-TLR (2.5% vs. 4.6%, p=0.001) for XIENCE V Compared to TAXUS Express

The largest prospective RCT comparing two DES platforms with clinical follow-up only, and 100% monitoring of all patient records, is the SPIRIT IV trial. Clinicians sought a trial not requiring angiographic follow-up (which tends to artificially increase TLR rates), one that was large enough to be powered to differentiate clinical outcomes like TLF, TLR, and death or MI. SPIRIT IV provides Level of Evidence A as classified by the ACC/AHA/SCAI Guidelines. The primary endpoint, presented at TCT 2009, shows significant reductions in target lesion failure (TLF) and ischemia-driven TLR for XIENCE V, and lower ARC-defined stent thrombosis risk with a one-year rate of 0.29% in a robust data set. 

In conclusion, 2009 has been an exciting year for patients. Currently, the XIENCE V stent is the only DES to show both angiographic and clinical superiority in prespecified clinical endpoints, over another DES in adequately powered prospective randomized trials while, at the same time, demonstrating statistically significantly lower stent thrombosis rates at one year. Our pipeline is rich across our endovascular and cardiovascular portfolios, and we are entering exciting new practice areas by acquisition and with our robust internal research and development.

Best regards,

Chuck Simonton, MD

Chief Medical Officer, Abbott Vascular

XIENCE V Indications and Important Safety Information

The XIENCE V Everolimus Eluting Coronary Stent on the MULTI-LINK MINI-VISION or MULTI-LINK VISION Delivery System

Indications

The XIENCE V Everolimus Eluting Coronary Stent System (XIENCE V stent) is indicated for improving coronary luminal diameter in patients with symptomatic heart disease due to de novo native coronary artery lesions (length £ 28 mm) with reference vessel diameters of 2.5 mm to 4.25 mm.

Contraindications

The XIENCE V stent is contraindicated for use in patients:

•    Who cannot receive antiplatelet and/or anti-coagulant therapy

•    With lesions that prevent complete angioplasty balloon inflation or proper placement of the stent or stent delivery system

•    With hypersensitivity or contraindication to everolimus or structurally-related compounds, cobalt, chromium, nickel, tungsten, acrylic, and fluoropolymers.

Warnings

•    Ensure that the inner package sterile barrier has not been opened or damaged prior to use.

•    Judicious patient selection is necessary because device use has been associated with stent thrombosis, vascular complications, and/or bleeding events.

•    This product should not be used in patients who are not likely to comply with the recommended antiplatelet therapy.

Precautions

•    Stent implantation should only be performed by physicians who have received appropriate training.

•    Stent placement should be performed at hospitals where emergency coronary artery bypass graft surgery is accessible.

•    Subsequent restenosis may require repeat dilatation of the arterial segment containing the stent. Long-term outcomes following repeat dilatation of the stent is presently unknown.

•    Risks and benefits should be considered in patients with severe contrast agent allergies.

•    Care should be taken to control the guiding catheter tip during stent delivery, deployment and balloon withdrawal. Use fluoroscopy to avoid arterial damage.

•    Stent thrombosis is a low-frequency event that current drug-eluting stent (DES) clinical trials are not adequately powered to fully characterize. Stent thrombosis is frequently associated with myocardial infarction (MI) or death.

•    When DES are used outside the specified Indications for Use, patient outcomes may differ from the results observed in the XIENCE V SPIRIT family of trials.

•    Compared to use within the specified Indications for Use, the use of DES in patients and lesions outside of the labeled indications, including more tortuous anatomy, may have an increased risk of adverse events, including stent thrombosis, stent embolization, MI, or death.  

•    Orally administered everolimus combined with cyclosporine is associated with increased serum cholesterol and triglycerides levels.

•    A patient’s exposure to drug and polymer is proportional to the number of and total length of implanted stents. See Instructions for Use for current data on multiple stent implantation.

•    Safety and effectiveness of the XIENCE V stent have not been established for subject populations with the following clinical settings:

•     Patients with prior target lesion or in-stent restenosis related brachytherapy, patients in whom mechanical atherectomy devices or laser angioplasty devices are used simultaneously, women who are pregnant or lactating, men intending to father children, pediatric patients, unresolved vessel thrombus at the lesion site, coronary artery reference vessel diameters < 2.5 mm or > 4.25 mm or lesion lengths > 28 mm, lesions located in saphenous vein grafts, unprotected left main coronary artery, ostial lesions, chronic total occlusions, lesions located at a bifurcation or previously stented lesions, diffuse disease or poor flow (TIMI < 1) distal to the identified lesions, excessive tortuosity proximal to or within the lesion, recent acute myocardial infarction (AMI) or evidence of thrombus in target vessel, moderate or severe lesion calcification, multivessel disease, in-stent restenosis, and patients with longer than 24 months follow-up

•    Everolimus has been shown to reduce the clearance of some prescription medications when it was administered orally along with cyclosporine (CsA). Formal drug interaction studies have not been performed with the XIENCE V stent because of limited systemic exposure to everolimus eluted from XIENCE V.

•    Everolimus is an immunosuppressive agent. Consideration should be given to patients taking other immunosuppressive agents or who are at risk for immune suppression.

•    Oral everolimus use in renal transplant patients was associated with increased serum cholesterol and triglycerides that in some cases required treatment.

•    Non-clinical testing has demonstrated that the XIENCE V stent, in single and in overlapped configurations up to 68 mm in length, is MR Conditional. It can be scanned safely under the conditions in the Instructions for Use.

•    The XIENCE V stent should be handled, placed, implanted, and removed according to the Instructions for Use.

Potential Adverse Events

Adverse events (in alphabetical order) which may be associated with coronary stent use in native coronary arteries include but are not limited to:

•    Abrupt closure, Access site pain, hematoma, or hemorrhage, Acute myocardial infarction, Allergic reaction or hypersensitivity to contrast agent or cobalt, chromium, nickel, tungsten, acrylic and fluoropolymers; and drug reactions to antiplatelet drugs or contrast agent, Aneurysm, Arterial perforation and injury to the coronary artery, Arterial rupture, Arteriovenous fistula, Arrhythmias, atrial and ventricular, Bleeding complications, which may require transfusion, Cardiac tamponade, Coronary artery spasm, Coronary or stent embolism, Coronary or stent thrombosis, Death, Dissection of the coronary artery, Distal emboli (air, tissue or thrombotic), Emergent or non-emergent coronary artery bypass graft surgery, Fever, Hypotension and / or hypertension, Infection and pain at insertion site, Injury to the coronary artery, Ischemia (myocardial), Myocardial infarction (MI), Nausea and vomiting, Palpitations, Peripheral ischemia (due to vascular injury), Pseudoaneurysm, Renal Failure, Restenosis of the stented segment of the artery, Shock/pulmonary edema, Stroke / cerebrovascular accident (CVA), Total occlusion of coronary artery, Unstable or stable angina pectoris, Vascular complications including at the entry site which may require vessel repair,  Vessel dissection

Adverse events associated with daily oral administration of everolimus to organ transplant patients include but are not limited to:

•    Abdominal pain, Acne, Anemia, Coagulopathy, Diarrhea, Edema, Hemolysis, Hypercholesterolemia, Hyperlipidemia, Hypertension, Hypertriglyceridemia, Hypogonadism male, Infections: wound infection, urinary tract infection, pneumonia, pyelonephritis, sepsis and other viral, bacterial and fungal infections, Leukopenia, Liver function test abnormality, Lymphocele, Myalgia, Nausea, Pain, Rash, Renal tubular necrosis, Surgical wound complication, Thrombocytopenia, Venous thromboembolism, Vomiting

Prior to use, please reference the Instructions for Use at www.abbottvascular.com/ifu for more information on indications, contraindications, warnings, precautions, and adverse events.

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