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SCD-HeFTSudden Cardiac Death in
Heart Failure Trial
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Sponsors
• NHLBI: All research costs at CCC, ICD Core, DCC, QoL
• 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 sub-study
• Knoll Pharmaceuticals: Meetings
• NIH Nursing Institute: Psychosocial sub-study
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Hypothesis
• Determine if amiodarone or ICD will decrease the risk of death from any cause in patients with mild-to-moderate heart failure
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Inclusion Criteria
• Symptomatic CHF (NYHA Class II and III) due to ischemic or non-ischemic dilated cardiomyopathy
• LVEF ≤ 35%
• ≥ 18 years of age; no upper age limitation
• CHF ≥ 3 months
• On optimal medical therapy for > 3 months
– Appropriate dose of ACE-I
– Beta blocker, if tolerated
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Exclusion Criteria
• Asymptomatic patients with LV dysfunction
• NYHA Class I or IV
• Class I ICD indications
• Pacemaker indications
• < 18 years
• Death expected ≤ 1 year due to cardiac causes
• Amiodarone or other AA drugs contraindicated
• Current Class I or II AA drugs
• Unexplained syncope ≤ 5 years
• AF patients requiring catheter ablation or amiodarone
• MI ≤ 30 days
• CABG or PTCA ≤ 30 days
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Centers
(2)
(2)
(2)
(3)
(2)
(2)
(4)
(2)
(8)
(2)
(2)
(2)
(3)
(2)
(2)
(5)(2)(3)
(3)
148 sites in the US, Canada,and New Zealand.
Enrollment 2521
(10)
(3)
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Endpoints
Primary: • Overall Mortality
Secondary:• Mortality: ischemic vs. non-ischemic
• Mortality: NYHA Class II vs. III
• Mortality by Sub Groups: age, gender, LVEF, MI Hx, time of MI, QRS width
• Cause-Specific Death
• HF Morbidity and Mortality
• Quality of Life
• Cost of Care and Cost-Effectiveness Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Protocol
DCM + CAD and CHF
Placebo N = 847 ICD Implant N = 829
Minimum of 2.5 years follow-up required
45 months average follow-up Optimized B, ACE-I, Diuretics
Amiodarone N = 845
EF < 35%
NYHA Class II or III
6-Minute Walk, Holter
R 2521 Patients
Bardy GH. N Engl J Med. 2005;352:225-237.
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 = 0.025 for each comparison
• Intention-to-treat study design
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Assessments Background Medical Therapies
• Electrocardiography
• 6-minute walk test
• 24-hour ambulatory electrocardiography
• Liver and thyroid function tests
• Chest radiography
• Drugs if required: beta blocker, ACE-I, aldosterone, aspirin, and statins
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT 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%
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Study Drug Dosing
• Outpatient administration
• < 800 mg qd for week 1
• < 400 mg qd for weeks 2-4
• Chronic dose weight dependent:
– 200 mg/d if < 150 lbs
– 300 mg/d if 150-200 lbs
– 400 mg/d if > 200 lbs
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT ICD Guidelines
• Medtronic Model 7223Cx – Micro Jewel® II
• Follow-Up: 1-week, 1-month, 3-month, then every 3 months
• Nominals:
– VF Settings: ON, 320 ms, NID 18/24, 30 J
– FVT and VT Settings: OFF
– VVI 50 (Hysteresis 34 bpm)
– Pre-VT/VF memory activation
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Baseline Patient Characteristics
AmiodaroneN = 845
PlaceboN = 847
ICDN = 829
NYHA II 71% 70% 68%
NYHA III 29% 30% 32%
Ischemic CHF 50% 53% 52%
Non-ischemic CHF 50% 47% 48%
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Baseline Patient Characteristics
AmiodaroneN = 845
PlaceboN = 847
ICDN = 829
Age (median) 60 60 60
Male 76% 77% 77%
Caucasian 77% 76% 77%
Weight (median) 190 190 190
SBP mm Hg (median) 118 120 118
DBP mm Hg (median) 70 70 70
Hypertension 56% 56% 55%
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Baseline Patient Characteristics
AmiodaroneN = 845
PlaceboN = 847
ICDN = 829
LVEF (median) 0.25 0.25 0.24
Diabetes 29% 32% 31%
Pulmonary Disease 17% 19% 21%
AF or Atrial Flutter 16% 14% 17%
NSVT 23% 21% 25%
Syncope 6% 7% 6%
Heart Rate bpm (median) 72 73 74
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Baseline Patient Characteristics
AmiodaroneN = 845
PlaceboN = 847
ICDN = 829
Hypercholesterolemia (median)
52% 54% 52%
EP study 18% 15% 16%
Serum Sodium mEq/liter(median)
139 139 139
Serum Creatinine mg/dl(median)
1.1 1.1 1.1
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Medication Use Last Follow-Up
AmiodaroneN = 845
PlaceboN = 847
ICDN = 829
ACE-I 71% 74% 70%
ARB 18% 17% 18%
ACE or ARB 85% 88% 86%
Beta Blocker 72% 79% 82%
Aspirin 56% 54% 55%
Warfarin 32% 36% 34%
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Medication Use Last Follow-Up
AmiodaroneN = 845
PlaceboN = 847
ICDN = 829
Digoxin 59% 62% 63%
Statin 48% 46% 48%
Diuretic:
Loop 79% 80% 79%
Potassium-Sparing 28% 33% 32%
Thiazide 11% 11% 10%
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Mortality Rate Overall Results
Months of Follow-Up
Mo
rtal
ity
Rat
e
483624120
Amiodarone
PlaceboICD
0.4
0.3
0.2
0.1
0.0
60
No. at RiskAmiodarone 845 772 715 484 280 97Placebo 847 797 724 505 304 89ICD 829 778 733 501 304 103
Hazard Ratio (97.5% Cl) P-ValueAmiodarone vs. Placebo 1.06 (0.86 - 1.30) 0.53ICD vs. Placebo 0.77 (0.62 - 0.96) 0.007
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Overall Mortality Results
Hazard Ratio (97.5% CI)
P-Value
Amiodarone vs. Placebo
1.06 (0.86 - 1.30) 0.53
ICD vs. Placebo
0.77 (0.62 - 0.96) 0.007ICDs reduce
mortality by 23%
Bardy GH. N Engl J Med. 2005;352:225-237.
0
5
10
15
20
25
30
35
40
Amiodarone Placebo ICD
SCD-HeFT 5-Year Mortality RateOverall Results
34% 36.1%
28.9%
Mo
rtal
ity
Rat
e
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Mortality Rate Ischemic CHF Patients
Months of Follow-Up
Mo
rtal
ity
Rat
e
483624120
Amiodarone
PlaceboICD
0.4
0.3
0.2
0.1
0.0
60
No. at RiskAmiodarone 426 384 346 227 130 46Placebo 453 415 370 244 152 48ICD 431 395 365 244 144 48
Hazard Ratio (97.5% Cl) P-ValueAmiodarone vs. Placebo 1.05 (0.91 - 1.36) 0.66ICD vs. Placebo 0.79 (0.60 - 1.04) 0.05
Bardy GH. N Engl J Med. 2005;352:225-237.
No. at RiskAmiodarone 419 388 369 257 150 51Placebo 394 382 354 261 152 41ICD 398 383 368 257 160 55
SCD-HeFT Mortality RateNon-Ischemic CHF Patients
Months of Follow-Up
Mo
rtal
ity
Rat
e
483624120
Amiodarone
PlaceboICD
0.4
0.3
0.2
0.1
0.0
60
Hazard Ratio (97.5% Cl) P-ValueAmiodarone vs. Placebo 1.07 (0.76 - 1.51) 0.65ICD vs. Placebo 0.73 (0.50 - 1.07) 0.06
0.5
Bardy GH. N Engl J Med. 2005;352:225-237.
05
101520253035404550
SCD-HeFT 5-Year Mortality RateIschemic vs. Non-Ischemic
41.7% 43.2%
21.4%25.8%
27.9%
35.9%
Ischemic Non-Ischemic
Ischemic Non-Ischemic
Ischemic Non-Ischemic
Amiodarone Placebo ICD
Mo
rtal
ity
Rat
e
Bardy GH. N Engl J Med. 2005;352:225-237.
No. at RiskAmiodarone 601 563 536 378 222 76Placebo 594 563 522 367 218 72ICD 566 550 531 371 236 80
SCD-HeFT Mortality RateNYHA Class II Patients
Months of Follow-Up
Mo
rtal
ity
Rat
e
483624120
Amiodarone
PlaceboICD0.4
0.3
0.2
0.1
0.0
60
Hazard Ratio (97.5% Cl) P-ValueAmiodarone vs. Placebo 0.85 (0.65 - 1.11) 0.17ICD vs. Placebo 0.54 (0.40 - 0.74) < 0.001
Bardy GH. N Engl J Med. 2005;352:225-237.
0.5
0.6
No. at RiskAmiodarone 244 209 179 106 58 21Placebo 253 234 202 138 86 17ICD 263 228 202 130 68 23
SCD-HeFT Mortality RateNYHA Class III Patients
Months of Follow-Up
Mo
rtal
ity
Rat
e
483624120
Amiodarone
PlaceboICD
60
Hazard Ratio (97.5% Cl) P-ValueAmiodarone vs. Placebo 1.44 (1.05 - 1.97) 0.010ICD vs. Placebo 1.16 (0.84 - 1.61) 0.30
Bardy GH. N Engl J Med. 2005;352:225-237.
0.4
0.3
0.2
0.1
0.0
0.5
0.6
0
10
20
30
40
50
60
SCD-HeFT 5-Year Mortality RateNYHA Class II vs. III
26.4%
32%
48.4%52.8%
45.6%
20%
NYHA II NYHA III NYHA II NYHA III NYHA II NYHA III
Amiodarone Placebo ICD
Mo
rtal
ity
Rat
e
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Mortality Results NYHA Class III Patients
• No survival benefits for ICD therapy in NYHA Class III patients in SCD-HeFT1
• These results are not consistent with other trial results and need to be further evaluated:
– DEFINITE Class III patients had the largest survival benefits with ICD therapy2
– Patients with the worst LVEF in MADIT-II and AVID trials had the largest benefit from ICD therapy3,4
1 Bardy GH. N Engl J Med. 2005;352:225-237. 2 Kadish A. N Engl J Med. 2004;350:2151-2158. 3 Moss AJ. N Engl J Med. 2002;346:877-883. 4 AVID Investigators. N Engl J Med. 1997;337:1576-1884.
SCD-HeFT Mortality Results Ischemic – Non-Ischemic and
NYHA Class II-III
Hazard Ratio (97.5% CI) ICD vs. Placebo
P-ValueReduction in Death w/ICD
Ischemic CHF 0.79 (0.60 -1.04) 0.05 21%
Non-Ischemic CHF 0.73 (0.50 - 1.07) 0.06 27%
NYHA Class II 0.54 (0.40 - 0.74) < 0.001 46%
NYHA Class III 1.16 (0.84 - 1.61) 0.30 None
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Discontinuations and Crossovers
Discontinue Study Rx
ICD Crossover
Amiodarone Crossover
Amiodarone 32%11%
Placebo 22% 10%
ICD 6% 14%
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Complications
Amiodarone (different than placebo):
• 4% increased tremor (P = 0.02)
• 6% increased hypothyroidism (P < 0.001)
ICD Therapy:
• 5% implant complications
• 9% follow-up complications
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT ICD Shock History Results
• 31% received shock for any reason
• 21% received shock for rapid VT or VF
• During 5 years follow-up the average annual rate of shock for rapid VT or VF was 5.1
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Rhythm Precursors to VT/VF
VT VF VT VF
Frequent Extra Systoles
52.3% 58.8% Decel. by > 100 ms of Prevailing Rhythms
7.3% 10.3%
Accel. > 100ms of Prevailing Rhythms
22.9% 22.1% Sustained SVT, not AF
7.3% 1.5%
Short-Long-Short Sequence
13.8% 32.4% Acute Onset AF 1.8% 1.5%
Initiating Beat of VT Morphology Different
20.2% NA VVI Pacing Triggered by Bradycardia
0% 4.4%
NSVT 11% 8.8% None Identified 17.4% 17.7%
Poole JE. Heart Rhythm 2005. May;2 (1suppl):AB20-5.
SCD-HeFT Change in NYHA ClassBaseline to 3 Years
Surviving patient’s HF condition appeared to improve progressively over time. Good drug management likely contributed to these results.
0
10
20
30
40
50
60
70
All ICD Placebo Amiodarone
% P
atie
nts
-2
-1
0
+1
+2
Changes in NYHA Class
Bardy GH. Heart Rhythm 2005. May;2 (1suppl):AB20-3.
SCD-HeFT Mode of Death
Cause of DeathAmiodarone
N = 845PlaceboN = 847
ICDN = 829
Cardiac 19% 20% 15%
Tachyarrhythmia 9% 11% 4%
Bradyarrhythmia < 1% < 1% < 1%
Heart Failure 8% 8% 9%
Nonarrhythmic 1% < 1% 1%
Packer DL. Heart Rhythm 2005. May;2 (1suppl):AB20-2.
SCD-HeFT Tachyarrhythmia Deaths
Cause of DeathAmiodarone
N = 845PlaceboN = 847
ICDN = 829
Tachyarrhythmia 9% 11% 4%
ICD therapy reduced tachyarrhythmia deaths by 60%
Packer DL. Heart Rhythm 2005. May;2 (1suppl):AB20-2.
SCD-HeFT Hazard Rate ResultsICD vs. Placebo
ICDBetter
4.02.01.00.50.25
Placebo Better
Subgroup ICD Therapy vs. Placebo
N Hazard Ratio (97.5% Cl)
Female Sex 382 0.96 (0.58 - 1.61)Male Sex 1294 0.73 (0.57 - 0.93)
Age < 65 Yrs 1098 0.68 (0.50 - 0.93)Age > 65 Yrs 578 0.86 (0.62 - 1.18)
White Race 1283 0.78 (0.61 - 1.00)Nonwhite Race 393 0.75 (0.48 - 1.17)
LVEF < 30% 1390 0.73 (0.57 - 0.92)LVEF > 30% 285 1.08 (0.57 - 2.07)
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Hazard Rate ResultsICD vs. Placebo
ICDBetter
4.02.01.00.50.25
PlaceboBetter
Subgroup ICD Therapy vs. Placebo
N Hazard Ratio (97.5% Cl)
QRS < 120 ms 977 0.84 (0.62 - 1.14)QRS > 120 ms 699 0.67 (0.49 - 0.93)6-Min Walk Test < 950 ft 526 1.14 (0.81 - 1.60) 950 – 1275 ft 536 0.57 (0.38 - 0.88) > 1275 ft 526 0.45 (0.27 - 0.76)
Beta Blocker 1157 0.68 (0.51 - 0.91)No Beta Blocker 519 0.92 (0.65 - 1.30)
Diabetes 524 0.95 (0.68 - 1.33)No Diabetes 1152 0.67 (0.50 - 0.90)
Bardy GH. N Engl J Med. 2005;352:225-237.
New SCD-HeFT Cost-Effectiveness Analysis
Incremental Cost-Effectiveness
Analysis1
SCD-HeFT2
Total Cost A – Total Cost B
Life Expectancy A – Life Expectancy B
=
$ Per Life-Year Saved
$LYS
1 Roberts PR. European Heart Journal. 2001;21:712-719.2 Mark DB. www.theheart.org. AHA News. November 11, 2004.
ICD
=$33,192 LYS
(discounted 3%lifetime analysis)
Placebo
$159,147 $90,759
10.78 Years* 8.41 Years*
* ICD patients had an average increase in life expectancy of 2.5 years
$0
$20,000
$40,000
$60,000
$80,000
$100,000
$120,000
$140,000
$160,000
$180,000
$200,000
Incremental Cost-EffectivenessCardiovascular Interventions
HypertensionTherapy(diastolic95 - 104mmHg)
Expensive
BorderlineCost-Effective
Cost-Effective
HighlyCost-Effective
Incr
emen
tal
Co
st p
er L
ife-
Yea
r S
aved
EconomicallyUnattractive
Lovastatin(chol. =
290 mg/dL,50 yrs old,
male, no riskfactors)
PTCA(chronic CAD,severe angina
1 VD)
CABG(chronic
CADmild angina,
3 VD)
End Stage Renal
Disease Treatment
Exercise SPECT (atypical
angina who can walk
on treadmill)
RoutineCoronary
Angiography(35 - 84 yrs
old, low risk MI,has CHF)
$8,461$17,701
$40,750
$67,000
$135,000
$150,000
Carotid Disease
Screening(65 yrs old,
male, no
symptoms)
$200,000
$120,000
$0
$20,000
$40,000
$60,000
$80,000
$100,000
$120,000
$140,000
$160,000
$180,000
$200,000
Incremental Cost-Effectiveness ICD, CRT, and CRT-D Therapies
COMPANIONCRT-D1
Incr
emen
tal
Co
st p
er L
ife-
Yea
r S
aved
COMPANIONCRT1
MADIT-IIICD3
AVIDICD4
$28,000 $38,200
$50,000$67,000
Expensive
BorderlineCost-Effective
Cost-Effective
HighlyCost-Effective
EconomicallyUnattractive
SCD-HeFTICD2
$33,000
1 Feldman AM. www.theheart.org. ACC News. March 16, 2005.2 Mark DB. www.theheart.org. AHA News. November 11, 2004.3 Ak-Khatib S. Ann Intern Med. 2005;142:593-600.4 Larsen G. Circulation. 2002;105:2049-2057.
SCD-HeFT Conclusions
• SCD-HeFT was the largest device trial (ICD, CRT, CRT-D) ever completed and had a longer follow-up period than other major device trials
• In NYHA Class II-III patients with LVEF ≤ 35% on optimal drug therapy:
– ICDs reduced mortality by 23%
– ICDs reduced tachyarrhythmia deaths by 60%
– Amiodarone did not improve survival
Bardy GH. N Engl J Med. 2005;352:225-237.
SCD-HeFT Conclusions
• ICD therapy provided the largest mortality reduction in NYHA Class II patients
• Surviving patients had improvements in their heart failure condition over time.Good drug management likely contributed to this improvement.
• Compared to other CV therapies, ICDs are a cost-effective therapy
SCD-HeFT Implications
• SCD-HeFT ischemic CHF results are similar to findings from recently completed post-MI ICD trials and provide additional support for ICD therapy in ischemic CHF patients
• SCD-HeFT non-ischemic CHF results support the new use of ICDs in the non-ischemic CHF patient population
• SCD-HeFT Class II results provide new evidence that “less sick” heart failure patients can benefit from ICD therapy
• Recent CMS Coverage Decisions allow reimbursement for all SCD-HeFT patients