SCD-HeFT: The Sudden Cardiac Death in Heart Failure Trial

Transcription

1 SCD-HeFT: The Sudden Cardiac Death in Heart Failure Trial Gust H. Bardy Seattle Institute for Cardiac Research Seattle, Washington

2 Disclosures Research grants, speaking fees Medtronic Research grants Wyeth Ayerst Research grants NIH (SCD-HeFT and HAT) Consulting fees, speaking fees Guidant Consulting fees, equity Cameron Health Research grants, consulting fees Phillips

3 2 Slides will be available on this afternoon

4 SCD-HeFT: The Sudden Cardiac Death in Heart Failure Trial American College of Cardiology 8 March 2004 Gust H. Bardy Seattle Institute for Cardiac Research Seattle, Washington 3

5 Central Research Team Gust Bardy: PI Kerry Lee: Study Biostatistician and Co-PI Daniel Mark: EQOL Jeanne Poole: ICD Core Lab Michael Domanski, Robin Boineau: NIH Milton Packer: DSMB, Chair Douglas Packer: Events Committee, Chair Ross Fletcher, Mason Platt: Holter Core Lab Frank Marchlinski: ICD Events Committee, Chair Clinical and Data Coordinating Center Staff: Charles Troutman, Jill Anderson, George Johnson, Steven McNulty, Beth Fraulo, Nancy Clapp-Channing, Linda Davidson Ray 4

6 SCD-HeFT Funding 5 U.S. National Institutes of Health (NHLBI): All research costs at CCC, ICD Core, DCC and EQOL Medtronic: Site clinical costs, ICD donations, meetings/travel Wyeth-Ayerst: Placebo and Amiodarone Duke University Pharmacy (Study drug distribution) Washington DC Veterans Hospital (Holter Core Lab) Cambridge Heart (Meetings, TWA Substudy) Knoll Pharmaceuticals (Meetings) NIH Nursing Institute (Psychosocial Substudy)

7 6 148 sites in US, Canada and New Zealand Enrollment = 2,521

8 Study Time Line First patient enrolled September 16, 1997 Enrollment ended July 19, 2001 Follow-up ended October 31, 2003 Data base locked March 1,

9 Hypothesis and Primary Endpoint To determine, by intention-to-treat analysis, if amiodarone or a conservatively programmed shock-only ICD reduces all-cause mortality compared to placebo* in patients with either ischemic or non-ischemic NYHA Class II and III CHF and EF < 35%. 8 *Double-blind for drug therapy

10 Study Power Calculations Predicted control mortality rate: 10% per year Presumed minimum follow-up: 2.5 years 90% power to detect a 25% in mortality in either amiodarone or ICD arm compared to placebo Alpha = for each comparison 9

11 Enrollment Scheme DCM + CAD and CHF EF < 35% NYHA Class II or III 6 minute walk, Holter R 10 Placebo Amiodarone ICD

12 Study Drug Dosing Outpatient administration < 800 mg qd for week 1 < 400 mg qd for weeks 2-4 Chronic dose is weight dependent 200mg/d if < 150 lbs 300mg/d if lbs 400mg/d if > 200 lbs 11

13 ICD Guidelines VVI-ICD (Medtronic 7223) VF therapy only FDI = 320ms, NID = 18/12 Hysteresis of 34 bpm (VVI = 50 bpm) Pre-VT/VF memory activation 12

14 Baseline Enrollment Characteristics Age 60.1 yrs (51.7, 68.5) median (25 th, 75 th percentiles) Female 23% Minorities 23% Heart rate 73 bpm (63,84) Blood Pressure Systolic 118 mmhg (106, 130) Diastolic 70 mmhg (62, 80) Weight 190 lbs (164, 219) 13

15 Baseline Enrollment Characteristics 14 CHF duration 24.5 mo (8.1, 59.4) LV EF 25.0 (20.0, 30.0) NYHA II, III 70%, 30% Ischemic, non-ischemic 52%, 48% 6 minute walk 1130 ft (840, 1360) Diabetes 30% CABG and/or Perc. Revasc. 37% H/O Hypertension 56% H/O Hyperlipidemia 53% H/O AF 15% H/O NSVT 23% ECG QRS duration 112 ms (96, 140), 41% > 120 ms

16 Background Medications Baseline Last follow-up ACE Inhibitor 85% 72% ACE Inhibitor or ARB 96% 87% Beta-blocker 69% 78% Spironolactone 19% 31% Loop diuretics 82% 80% Aspirin 56% 55% Statin 38% 47% 15 Median follow-up 45.5 months

17 Mortality by Intention-to-treat Median follow-up: 45.5 mo (34.8, 55.2) Vital status known on 100% of 2,521 patients 36.1% 7.2%/year Mortality Amiodarone ICD Therapy Placebo Months of follow-up

18 Mortality by Intention-to-treat HR 97.5% CI P-Value Amiodarone vs. Placebo , Mortality Amiodarone ICD Therapy Placebo Months of follow-up

19 Amiodarone vs. Placebo Hazard Ratios Patient Group All Patients N HR 97.5% CI , 1.30 NYHA Class Class II Class III , , 1.97 Ischemic CHF Etiology Non-Ischemic , ,

20 Additional Subgroups: Amiodarone vs. Placebo Patient Group N HR 97.5% CI Gender Female Male , , 1.30 LVEF 30% > 30% , , 2.31 Age < , , 1.52 QRS Duration < 120 ms 120 ms , , 1.41 Race White , 1.34 Non-White , 1.62 Enrolling Country U.S. Non-U.S , , 1.84 Beta Blocker Yes No , , 1.38 Diabetes Yes No , ,

21 Mortality by Intention-to-treat HR 97.5% CI P-Value Amiodarone vs. Placebo , ICD Therapy vs. Placebo , Mortality Amiodarone ICD Therapy Placebo Months of follow-up

22 ICD vs. Placebo Hazard Ratios All Patients Patient Group N HR 97.5% CI , 0.96 NYHA Class Class II Class III , , 1.61 Ischemic CHF Etiology Non-Ischemic , ,

23 Additional Subgroups: ICD vs. Placebo 22 Patient Group N HR 97.5% CI Gender Female Male , , 0.93 LVEF 30% > 30% , , 2.07 Age < , , 1.18 QRS Duration < 120 ms 120 ms , , 0.93 Race White , 1.00 Non-White , 1.17 Enrolling Country U.S. Non-U.S , , 0.82 Beta Blocker Yes No , , 1.30 Diabetes Yes No , ,

24 SCD-HeFT: Conclusions In class II or III CHF patients with EF < 35% on good background drug therapy, the mortality rate for placebo-controlled patients is 7.2% per year over 5 years Simple, shock-only ICDs decrease mortality by 23% Amiodarone, when used as a primary preventative agent, does not improve survival 23

25 Question and Answer Session SCD-HeFT: The Sudden Cardiac Death in Heart Failure Trial Gust H. Bardy Seattle Institute for Cardiac Research Seattle, Washington 24