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Vol 122, No 21

November 23, 2010

2010 Clinical Trial/Clinical Science Abstracts

Late-Breaking Clinical Trials I

Hall B Abstracts 21768–21828

21768 The Resynchronization/Defibrillation for Ambulatory Heart Failure Trial (RAFT)

Anthony S Tang, George A Wells, Univ of Ottawa Heart Institute, Ottawa, Canada; Mario Talajic, Institut de Cardiologie de Montre´al, Montreal, Canada; J. Malcolm O Arnold, Univ Hosp, London Health Sciences Cntr, London, Canada; Robert Sheldon, Libin Cardiovascular Institute of Alberta, Calgary, Canada; Stuart Connolly, Hamilton Health Science Cntr, Hamilton, Canada; Stefan H Hohnloser, J.W. Goethe Universitat, Frankfurt, Germany; Graham Nichol, Univ of Washington-Harborview Med Cntr, Seattle, WA; David H Birnie, Univ of Ottawa Heart Institute, Ottawa, Canada; John L Sapp, Queen Elizabeth II Health Sciences Cntr, Halifax, Canada; Raymond Yee, London Health Sciences Cntr, London, Canada; Jeffrey S Healey, McMaster Univeristy, Hamilton, Canada; Jean L Rouleau; Universite´ de Montre´al, Montreal, Canada

The role of cardiac resynchronization therapy (CRT) in patients with mild to moderate heart failure (HF) symptoms requiring an implantable cardioverter-defibrillator therapy (ICD) remains uncertain. We hypothesized that the addition of CRT to optimal medical therapy and ICD reduces mortality and HF hospitalization in patients with mild to moderate HF symptoms, LV dysfunction (EF less than or equal to 30%) and wide QRS duration. Design: This study is a prospective multicenter (34 sites in Canada, Europe, Australia, and Turkey) randomized double-blinded controlled clinical trial. Patients were randomized to receive an ICD (control) or ICD with CRT in a 1:1 ratio in addition to optimal heart failure medical therapy. The primary endpoint is a composite of all cause mortality and adjudicated HF hospitalization (defined as an admission to hospital for 24 hrs with a diagnosis of worsening HF) whichever comes first. Secondary endpoints include all cause mortality at anytime during the study, HF hospitalization, quality of life and cost effectiveness of therapy. Sample size: A total of 1798 patients satisfying the inclusion/exclusion criteria were enrolled between January 2003 and February 2009. The study was designed to achieve 85% power to detect a 25% relative risk reduction in the primary end-point with a minimum follow-up of 18 months accounting for a projected loss to follow-up of 2%, crossover of 5% and 7% and a projected annual event rate of 11% in the control group. Study population: At baseline, the mean age was 66 years; 82% were male; mean LVEF was 23%; 67% had ischemic cardiomyopathy; 13% had permanent atrial fibrillation; conducted QRS duration was 158 ms and paced QRS duration was 209 ms. Results: We anticipate that the primary endpoint will have been reached in 580 patients with

  • 390 patient deaths at any time during a mean follow-up of 36 months; 330 patients had

at least one adjudicated HF hospitalization. The final data analysis with the intention-to-treat principle of primary and major secondary endpoints will be completed in September and will be available for the AHA presentation.

Author Disclosures: A.S. Tang: Research Grant; Modest; St Jude Medical. Research Grant; Significant; Medtronic. Honoraria; Modest; Sanofi-Aventis, Boehringer-Ingelheim. G.A. Wells: Research Grant; Significant; Medtronic. M. Talajic: Research Grant; Modest; Medtronic, Boston Scientific, St. Jude Medical, Sorin. Consultant/Advisory Board; Modest; Medtronic. J.O. Arnold: Research Grant; Modest; Medtronic. Honoraria; Modest; Medtronic. Consultant/Advisory Board; Modest; Medtronic. R. Sheldon: None. S. Connolly: Research Grant; Significant; Boston Scientific, St. Jude Medical. S.H. Hohnloser: Sanofi Aventis, St. Jude Medical. Speakers Bureau; Modest; St. Jude Medical, Sanofi Aventis, ARYx, Boehringer Ingelheim. Honoraria; Modest; St. Jude Medical, Boehringer Ingelheim, ARYx, Cardiome, MSD. Ownership Interest; Significant; Sanofi Aventis. Consultant/Advisory Board; Modest; St. Jude Medical, Boehringer Ingelheim, ARYx, Cardiome, MSD, Boston Scientific, Sanofi Aventis. G. Nichol: Research Grant; Significant; Medtronic. Consultant/Advisory Board; Modest; Gambro Renal Inc., Sotera Wireless, Lifebridge Medizintechnik AG. D.H. Birnie: Research Grant; Significant; Medtronic Inc. Speakers Bureau; Modest; Medtronic Inc. J.L. Sapp: Research Grant; Significant; St. Jude Medical, Biosense Webster. Honoraria; Modest; St. Jude Medical, Biosense Webster. R. Yee: Research Grant; Significant; Medtronic of Canada. Speakers Bureau; Modest; Medtronic of Canada. Consultant/Advisory Board; Modest; Medtronic Inc.. J.S. Healey: None. J.L. Rouleau: None.

21723 Evaluation of the HeartWare® HVAD Left Ventricular Assist Device System for the Treatment of Advanced Heart Failure: Results of the ADVANCE Bridge to Transplant Trial

Keith D Aaronson, Univ of Michigan, Ann Arbor, MI; Mark S Slaughter, Univ of Louisville, Louisville, KY; Edwin McGee, William G Cotts, Northwestern Univ, Chicago, IL; Michael A Acker, Mariell L Jessup, Univ of Pennsylvania, Philadelphia, PA; Igor D Gregoric, Pranav Loyalka, Texas Heart Institute, Houston, TX; Valluvan Jeevanandam, Allen S Anderson, Univ of Chicago, Chicago, IL; Robert L Kormos, Jeffrey J Teuteberg, Univ of Pittsburgh, Pittsburgh, PA; Francis D Pagani, Univ of Michigan, Ann Arbor, MI; Steven Boyce, Washington Hosp Cntr, Washington, DC; David Hathaway, HeartWare, Inc, Framingham, MA; Leslie W Miller, Washington Hosp Cntr, Washington, DC; Michael A Acker; Univ of Pennsylvania, Philadelphia, PA

Background: Improved outcomes with ventricular assist devices have been demonstrated in continuous flow pumps utilizing axial flow technology compared to older pulsatile designs. The

HeartWare HVAD is a small, durable, centrifugal flow pump implanted directly in the left ventricular apex and contained within the pericardial space. The centrifugal flow pattern combined with the smaller size and no space requirement may result in improved clinical outcomes. We report the outcomes of ADVANCE, a multicenter, prospective trial in advanced heart failure patients listed for transplantation who have failed medical therapy. Methods: The study hypothesis is that the primary composite endpoint, the proportion of patients alive, transplanted or explanted for recovery and without device replacement at 180 days, will be noninferior to that of a contemporaneous control group undergoing bridge to transplant (BTT) with commercially available left ventricular assist devices and enrolled in the INTERMACS Registry. With a noninferiority margin of 15%, the trial design and sample sizes provide 90% power to test the primary hypothesis at the one-sided 0.05 significance level. Results: 140 adults (28%F, 72%M; 43% ischemic) listed for transplant as UNOS status 1A or 1B, with BSA1.2 cm received HVADs as BTT at 30 sites. Baseline characteristics for HVAD patients included (meanSD): age 53.510.3 (range 22–70) years, BSA 2.10.3 m2, LVEF 17.97.0%, CI 2.00.7 L/min/m2, mean BP 76.612.6 mmHg, PCW 22.38.8 mmHg, PA systolic 51.115.5 mmHg. Over 85% of patients were receiving one or more intravenous inotropes and 25% were supported with an IABP at HVAD implantation. Conclusions: The primary endpoint and survival will be compared between HVAD patients and contemporaneous control patients from INTERMACS. Adverse events, operative times and transfusion require- ments will also be reviewed. In addition, we will present quality of life and functional outcomes for the HVAD patients. As the first FDA pivotal trial to incorporate a comparison against controls from the NIH-sponsored INTERMACS Registry, ADVANCE’s novel design provides a model for investigation of future devices.

Author Disclosures: K.D. Aaronson: Research Grant; Modest; HeartWare, Terumo. Consultant/ Advisory Board; Modest; HeartWare. M.S. Slaughter: Research Grant; Modest; HeartWare. E. McGee: Consultant/Advisory Board; Modest; Thoratec. Consultant/Advisory Board; Significant; HeartWare. W.G. Cotts: None. M.A. Acker: Consultant/Advisory Board; Modest; Acorn, Thoratec, HeartWare. M.L. Jessup: HeartWare. I.D. Gregoric: None. P. Loyalka: None. V. Jeevanandam: ; HeartWare, Thoratec, Terumo. A.S. Anderson: None. R.L. Kormos: None. J.J. Teuteberg: Speakers Bureau; Modest; XDx. Consultant/Advisory Board; Modest; Thoratec, XDx. F.D. Pagani: Research Grant; Modest; HeartWare, Terumo, Thoratec. Consultant/Advisory Board; Modest; HeartWare. S. Boyce: Ownership Interest; Significant; HeartWare. Consultant/ Advisory Board; Modest; HeartWare. D. Hathaway: Employment; Significant; HeartWare. Ownership Interest; Significant; HeartWare. L.W. Miller: Research Grant; Significant; Heart- Ware, Thoratec. Honoraria; Modest; HeartWare, Thoratec. M.A. Acker: Consultant/Advisory Board; Modest; Acorn Cardiovascular, Ic.

23221 The Effect of Eplerenone versus Placebo on Cardiovascular Mortality or Heart Failure Hospitalization in Subjects With NYHA Class II Chronic Systolic Heart Failure. EMPHASIS-HF

Faiez Zannad, INSERM, CIC 9501 and U961, Univ of Nancy, Vandoeuvre les Nancy, France; McMurray J John, British Heart Foundation Cardiovascular Rsch Cntr, Univ of Glasgow, Glasgow, United Kingdom; Drexler Helmut, Clinic of Cardiology and Angiology, Hannover Med Sch,, Hannover, Germany; Krum Henry, Monash Univ, Cntr of Cardiovascular Rsch and Education in Therapeutics, Melbourne, Australia; Van Veldhuisen J Dirk, Thorax Cntr, Groningen, Netherlands; Swedberg Karl, Sahlgrenska Academy, Univ of Gothenburg, Gothenburg, Sweden; Pitt Bertram; Univ of Michigan, Ann Arbor, MI

The effect of eplerenone versus placebo on cardiovascular mortality or heart failure hospitalization in subjects with NYHA class II chronic systolic heart failure. EMPHASIS-HF Purpose: In chronic heart failure (HF), aldosterone antagonists have been shown to improve survival in patients with low ejection fraction and moderate-to-severe symptoms (NYHA III and IV). Efficacy of these agents was also shown when they were administered to patients with left ventricular dysfunction and signs and symptoms of CHF early after acute myocardial infarction. It is not known whether the selective aldosterone antagonist eplerenone can improve outcomes in mildly symptomatic patients. The Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure (EMPHASIS-HF) was designed to evaluate the effect of eplerenone on mortality and morbidity in patients with chronic systolic HF in NYHA class II Methods: A total of 2681 patients with ejection fraction 30% and estimated glomerular filtration rate 30 mL/min/ 1.73 m2 have been recruited. Patients were randomized 1:1 to double-blind eplerenone or placebo in addition to standard chronic HF therapy. Doses were adjusted from 25 mg every other day to 50 mg daily, depending on serum potassium. The primary endpoint is a composite of time to cardiovascular death or first hospital admission for worsening HF, whichever occurs first Results and Conclusions: EMPHASIS-HF has prema- turely reached its primary endpoint according to the predefined stopping rules. Full results will be presented at the meeting.

Author Disclosures: F. Zannad: Consultant/Advisory Board; Significant; Pfizer. M.J. John: pfizer. D. Helmut: None. K. Henry: pfizer. V.J. Dirk: pfizer. S. Karl: pfizer. P. Bertram: Ownership Interest; Significant; relypsa. Consultant/Advisory Board; Significant; pfizer.

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