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2010 Late-Breaking Clinical Trial Abstracts and Clinical Science: Special Reports Abstracts


21828 Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure Trial (ASCEND-HF)

Adrian F Hernandez, Christopher M O’Connor, Duke Clinical Rsch Institute, Durham, NC; Randall C Starling, Cleveland Clinic, Cleveland, OH; Paul W Armstrong, Univ of Alberta, Edmonton, Canada; Kenneth Dickstein, Univ of Bergen, Bergen, Norway; Daniel Gennivois, Johnson & Johnson, Raritan, NJ; Vic Hasselblad, Gretchen M Heizer, Duke Clinical Rsch Institute, Durham, NC; Michel Komajda, Univ Pierre Marie Curie, Paris, France; Barry Massie, Univ of California, San Francisco, San Francisco, CA; John J McMurray, Western Infirmary, Glasgow, Scotland, United Kingdom; Markku Nieminen, Meilahti Hosp, Helsinki, Finland; Craig J Reist, Duke Clinical Rsch Institute, Durham, NC; Jean L Rouleau, Montreal Heart Institute, Montreal, Canada; Karl Swedberg, Sahlgrenska Academy, Goteberg, Sweden; Robert M Califf; Duke Translational Medicine Institute, Durham, NC

Background. Nesiritide is a recombinant intravenous formulation of human B-type natriuretic peptide known to reduce dyspnea and intracardiac filling pressures wihtin 3 hours of administration in patients with acute decompensated heart failure (ADHF). However, the effect of nesiritide on dyspnea at 6 or 24 hours is unknown. Morevoer no clinical outcome trial exists that provides a reliable estimate of the effect of nesiritide on morbidity and mortality. Methods. In a prospective, double-blind randomized trial,ADHF patients within 24 hours of hospitalization were randomly assigned to receive either intravenous nesiritide or matching placebo for between 24 hours to 7 days. The 2 co-primary endpoints are (1) assessment of acute dyspnea at 6 or 24 hours, and (2) death or rehospitalization for HF within 30 days. Results: Enrollment will end in August, 2010 with the prespecified 7000 subjects from approximately 400 sites worldwide. Current baseline characteristics show that the median age is 68 years (25th/75th interquartile range (IQR): 57 yrs-77yrs) and 34% of subjects are female. Ischemic heart disease is present in 60% and the median ejection fraction is 30% (25th/75th IQR: 20%, 37%): 22% have an ejection fraction 40%. Treatment pre-randomization included loop diuretics in

    • 95.3

      %, inotropes in 4.4%, and vasodilators in 14.8%. A bolus of study drug was used in

    • 61.3

      % of patients and the median duration of study drug infusion was 42.2 hours

(25th/75th IQR: 24.1, 48.6 hrs). Last 30-day follow-up visit will occur in September, 2010. Conclusions. The data from the ASCEND-HF trial will evaluate whether nesiritide safely improves acute dyspnea at 6 or 24 hours as well as all-cause mortality and rehospital- ization for heart failure at 30 days.

Author Disclosures: A.F. Hernandez: Research Grant; Significant; Johnson & Johnson. Honoraria; Modest; Amgen, Corthera. C.M. O’Connor: Research Grant; Significant; Johnson & Johnson. Other Research Support; Significant; Merck. R.C. Starling: Research Grant; Modest; Johnson & Johnson. P.W. Armstrong: Research Grant; Significant; Johnson & Johnson. K. Dickstein: Johnson & Johnson. D. Gennivois: Employment; Significant; Johnson & Johnson. V. Hasselblad: None. G.M. Heizer: None. M. Komajda: Research Grant; Significant; Johnson & Johnson. B. Massie: Johnson & Johnson. J.J. McMurray: Johnson & Johnson. M. Nieminen: Johnson & Johnson. C.J. Reist: None. J.L. Rouleau: Johnson & Johnson. K. Swedberg: Johnson & Johnson. R.M. Califf: Johnson & Johnson.

Late-Breaking Clinical Trials II

Hall B Abstracts 21839–21752

21839 Stroke Prevention Using the Oral Direct Factor Xa Inhibitor Rivaroxaban Compared With Warfarin in Patients With Nonvalvular Atrial Fibrillation (ROCKET AF)

Manesh R Patel for ROCKET AF Executive Steering Committee; Duke Univ, Durham, NC

Background: Anticoagulation with warfarin prevents ischemic stroke in patients with nonvalvular atrial fibrillation (AF), but routine coagulation monitoring, dose adjustments, and bleeding risk limit its overall use. The oral direct Factor Xa inhibitor rivaroxaban represents a potential alternative anticoagulant. Objective: To establish whether rivaroxaban is noninferior to dose-adjusted warfarin within a risk ratio margin of 1.46 for the prevention of all stroke and systemic embolic events. Methods: Patients with AF and a history of stroke or at least 2 stroke risk factors (n14,269) were randomized at 1215 participating sites in 45 countries to receive either rivaroxaban, 20 mg daily, or dose-adjusted warfarin (target INR 2.5, range 2.0–3.0) double-blind. The primary efficacy endpoint was all adjudicated strokes (ischemic and hemorrhagic) and systemic embolic events. The primary analysis was based on establishing noninferiority in the per-protocol population. Results: These data are preliminary as final follow up and database closure is underway. The median patient age was 73 years; 40% were female, 63% had heart failure, 90% hypertension, 40% diabetes, and 55% a prior stroke or TIA. The intrinsic stroke risk of enrolled patients was high (tk% had a CHADS2 score 3). The trial was stopped when the prespecified 405 per protocol primary efficacy events had occurred. During tk patient-years of exposure (median 42 months), the INR on warfarin (mean tk) was within target range tk% of the time. At time of presentation, primary event rates, the absolute difference in primary event rates, all-cause mortality, rates of disabling or fatal stroke, hemorrhagic stroke and major bleeding will be reported. Conclusion: The ROCKET AF study will define the efficacy and safety of rivaroxaban as an alternative to warfarin for the prevention of stroke and systemic embolism in patients with nonvalvular AF.

Author Disclosures: M.R. Patel for ROCKET AF Executive Steering Committee: None.

21780 Primary Results From the SMART AV Trial: A Randomized Trial Comparing Empiric, Echocardiographic Guided and Algorithmic AV Delay Programming in Cardiac Resynchronization Therapy (CRT)

Kenneth A Ellenbogen, Med College of Virginia, Richmond, VA; Michael Gold, Med Univ of South Carolina, Charleston, SC; Bernd Lemke, Ruhr-Universit¨at Bochum, Bochum, Germany; Ignacio Lozano, Hosp Puerta de Hierro, Madrid, Spain; Timothy Meyer, Boston Scientific, St. Paul, MN; Suneet Mittal, The St. Luke’s-Roosevelt Hosp Cntr, New York, NY; Jagmeet Singh, Massachusetts General Hosp, Harvard Med Sch, Boston, MA; Francis Spinale, Med Univ of South Carolina, Charleston, SC; Kenneth Stein, Boston Scientific, St. Paul, MN; Jennifer Van Eyk, Johns Hopkins Univ, Baltimore, MD; Alan Waggoner; Washington Univ Sch of Medicine, St. Louis, MO

Introduction: A number of small non-randomized studies have suggested optimization of the atrioventricular (AV) interval may improve response to CRT therapy. There are no large prospective randomized trials comparing the clinical and echocardiographic outcomes after AV interval optimization. Approximately 30% of patients who receive a CRT device experience a limited benefit in heart failure (HF) symptoms and/or reverse left ventricular (LV) remodeling. One variable that may influence response can be the programmed AV delay. The SMART AV Trial prospectively randomized patients to a fixed empiric AV delay, echocardiographic optimization of AV delay, or AV delay optimization based on the SmartDelay™ algorithm. The SmartDelay algorithm is an electrogram based method derived from invasive hemodynamic studies that measured acute changes in LV dP/dtmax with biventricular pacing. Methods: 1014 patients (68% male, mean age 6611 years, mean LVEF: 25%7%) who met enrollment criteria received a CRT-D, and were randomized in 1:1:1 ratio to three arms: AV delay set at 120 msec, AV delay programmed using echocardiography (mitral inflow method) or AV delay programmed using the SmartDelay algorithm. Patients were programmed to either DDD or DDDR with a lower rate of 60 and were evaluated at baseline and 3-and 6-months post-implant. Variables measured included: clinical status (NYHA class, quality of life score, 6 minute walk distance, HF hospitalization), plasma biomarker profiles, and 2D echocardiograph- ic derived LV volumes. Results: The primary endpoint of changes in left ventricular end-systolic volume at 6 months between the three groups will be presented. Secondary endpoints including NYHA classification, 6 minute walk distance, changes in quality of life and HF hospitalizations will be presented. Initial results regarding changes in biomarker profiles as they relate to the primary endpoint will also be presented. Conclusion: The SMART-AV trial measured the effects of AV optimization by different methods on structural and functional outcomes. The potential implications for non-responders will be discussed.

Author Disclosures: K.A. Ellenbogen: Research Grant; Significant; Medtronic, Boston Scientific, St. Jude Medical, Biosense Webster, Sanofi Aventis. Speakers Bureau; Significant; Medtronic, Boston Scientific, St. Jude Medical, Biotronik, Sanofi Aventis. Honoraria; Significant; Medtronic, Boston Scientific, St. Jude Medical, Biotronik, Sanofi Aventis, Glaxo Smith Kline. Consultant/ Advisory Board; Significant; Medtronic, Boston Scientiific, St. Jude Medical, Cardionet, Atricure, EBR, Biotronik. M. Gold: Research Grant; Modest; Sorin. Research Grant; Significant; Boston Scientific, Medtronic, St. Jude Medical. Honoraria; Modest; Sorin. Honoraria; Significant; Boston Scientific, Medtronic. Consultant/Advisory Board; Significant; Boston Scientific, Medtronic. B. Lemke: Honoraria; Modest; Boston Scientific, Medtronic, St. Jude Medical, Biotronik, Sorin Biomedical. I. Lozano: St. Jude Medical, Biotronik. Consultant/Advisory Board; Modest; Boston Scientific, Sorin Biomedical. Other; Significant; Medtrinic, St. Jude Medical. T. Meyer: Employment; Significant; Boston Scientific. Ownership Interest; Significant; Boston Scientific. S. Mittal: Honoraria; Modest; Boston Scientific, Johnson & Johnson, Medtronic, St. Jude Medical, Biotronik. Consultant/Advisory Board; Significant; Biotronik, Lifewatch. Other; Significant; Bard, Biotronik, Boston Scientific, Medtronic, St. Jude Medical. J. Singh: Research Grant; Significant; Boston Scientific, Medtronic, Biotronik, St. Jude Medical. Honoraria; Modest; Boston Scientific, Medtronic, Biotronik, St. Jude Medical, Sorin Biomedical. Consultant/Advisory Board; Modest; Boston Scientific, Medtronic, Biotronik, St. Jude Medical, Sorin Biomedical. F. Spinale: Research Grant; Significant; National Institutes of Health, VA Health Administration. Consul- tant/Advisory Board; Modest; Boston Scientific, Acorn Cardiovascular. K. Stein: Employment; Significant; Boston Scientific. Ownership Interest; Significant; Boston Scientific. J. Van Eyk: None. A. Waggoner: Honoraria; Modest; Boston Scientific, St. Jude Medical.

21811 Efficacy and Safety of Prescription Omega-3-Acid Ethyl Esters (P-OM3) for the Prevention of Recurrent Symptomatic Atrial Fibrillation (AF)

Peter R Kowey, Main Line Health Heart Cntr Lankenau Hosp, Wynnewood, PA; James A Reiffel, Columbia Univ Med Cntr, New York, NY; Kenneth A Ellenbogen, Virginia Commonwealth Univ Med Cntr, Richmond, VA; Gerald V Naccarelli, Penn State Univ College of Medicine, Hershey, PA; Craig M Pratt; Methodist DeBakey Heart & Vascular Cntr, Houston, TX

Objectives: AF is common and usually requires therapy; yet, current treatments have limited efficacy and untoward side effects. Data from several small trials suggest antiarrhythmic benefits of omega-3 polyunsaturated fatty acids may be effective and are safe. We conducted a prospective, randomized, double-blind study to evaluate safety and efficacy of P-OM3 in patients with confirmed symptomatic paroxysmal or persistent AF. Methods: Subjects with symptomatic AF without significant structural heart disease were eligible. Concomitant antiarrhythmic drugs were not allowed. The primary endpoint was time to first recurrence of symptomatic AF in patients with paroxysmal AF. Secondary analyses included the time to first recurrence in the persistent stratum and the groups combined. Results: A total of 663 patients with paroxysmal or persistent AF (5:1 stratification) were randomly assigned to P-OM3 4g/d or placebo and treated for 24 weeks. The treatment groups and strata were well matched with regard to demographics and baseline characteristics and had a mean age of 61 yrs, was 56% male, with 67% concomitant beta blocker use, 45% statin use, 39% ACE/ARB use; 62% had hypertension, 17% had CAD, and 3% had clinically significant abnormal baseline ECHO. There was no difference between treatment groups in the time to first recurrence of symptomatic AF in the paroxysmal stratum (HR 1.15, CI 0.9–1.46, p0.263). Similar results were observed in the persistent stratum and both groups combined. Secondary analyses support the primary

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