DualChamber and VVI Implantable Defibrillator Trial DAVID

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Dual-Chamber and VVI Implantable Defibrillator
TrialDAVID
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DAVID Trial Overview

• Hypothesis
• Aggressive management of LV dysfunction with
  optimized drug therapy and with dual chamber
  pacing could improve the combined endpoint of
  total mortality and hospitalization for heart
  failure, compared to similarly optimized drug
  therapy supported by ventricular backup pacing.
• Study design
• Single blind, multicenter, parallel group,
  randomized trial comparing DDDR (70 bpm lower
  rate) vs. VVI (40 bpm lower rate) pacing modes

Wilkoff B, et al. JAMA. 2002 288 3115-3123.
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DAVID Trial Endpoints

• Primary
• Freedom from death and heart failure
  hospitalization

Wilkoff B, et al. JAMA. 2002 288 3115-3123.
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DAVID Trial Inclusion Criteria

• ICD indicated patients
• No indication for antibradycardia pacing
• LVEF ?40
• No persistent or frequent, uncontrolled AF

Wilkoff B, et al. JAMA. 2002 288 3115-3123.
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DAVID Trial Baseline Patient Characteristics
Wilkoff B, et al. JAMA. 2002 288 3115-3123.
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DAVID Trial Baseline Patient Characteristics
Wilkoff B, et al. JAMA. 2002 288 3115-3123.
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DAVID Trial Protocol
760 assessed for eligibility
250 excluded 149 Did not meet Rx criteria
55 refused 46 Other
510 eligible
4 Not randomized 2 Required pacing 1
Inadequate defibrillation threshold 1 Decided
not to implant
VVI-40 (n256)
DDDR-70 (n 250)

• 1 had pacing mode set to DDD
• 1 LTF
• 10 Discontinued intervention
• 5 Bradycardia
• 1 CHF and AF
• 1 Brady induced Torsade
• 1 Heart Tx workup
• 1 AF w rapid V response
• 1 multiple shocks due to double counting

• 3 had pacing mode set to VVI
• 2 LTF
• 5 Discontinued intervention
• 1 Angina
• 1 CHF and Lead Failure
• 1 CHF Hospitalization
• 1 Exacerbation of VT
• 1 Lead Migration

Wilkoff B, et al. JAMA. 2002 288 3115-3123.
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DAVID Trial Drug Therapy 6 Months Post
Randomization
Wilkoff B, et al. JAMA. 2002 288 3115-3123.
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DAVID
Death or First Hospitalization for New or
Worsened CHF
0.4
DDDR
Hazard ratio (95 CI), 1.61 (1.06-2.44)
0.3
Cumulative Probability
0.2
VVI
0.1
0
0
6
12
18
Months
No. at Risk DDDR VVI
250 256
159 158
76 90
21 25
Wilkoff B, et al. JAMA. 2002 288 3115-3123.
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DAVID Trial Results
Wilkoff B, et al. JAMA. 2002 288 3115-3123.
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DAVID
First Hospitalization for New or Worsened CHF
0.4
0.3
Hazard ratio (95 CI), 1.54 (0.97-2.46)
DDDR
Cumulative Probability
0.2
VVI
0.1
0
0
6
12
18
Months
No. at Risk DDDR VVI
250 256
155 156
74 89
21 24
Wilkoff B, et al. JAMA. 2002 288 3115-3123.
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DAVID
Death From Any Cause
Wilkoff B, et al. JAMA. 2002 288 3115-3123.
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DAVID
Wilkoff B, et al. JAMA. 2002 288 3115-3123.
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DAVID

• Study results are consistent with the pacing
  literature.
• AAI was associated with slightly better survival
  and lower rate of severe CHF compared to VVI
  pacing mode in patients with SSS1
• QOL was better in elderly patients with sinus
  node disease with VVI compared to DDD pacing.2
• More than 40 ventricular pacing was associated
  with increased CHF hospitalizations.3
• The benefit of DDDR pacing was most evident in
  patients who needed continuous pacing.4

• Sweeney et al. Pacing Clin Electro. 200225690.
• Kerr et al. Pacing Clin Electro. 200225553.

• Anderson et al. Lancet. 19973501210-1216.
• Lamas et al. N Engl J Med. 19973371576-1583.

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DAVID Conclusions

• Bradycardia pacing operation in dual-chamber ICDs
  should be optimized for individual patients.
• RV pacing in patients with LV dysfunction and no
  bradycardia indication for pacing can be harmful.
• Programming of dual chamber devices to backup
  ventricular pacing is justified in this patient
  population.

Wilkoff B, et al. JAMA. 2002 288 3115-3123.
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DAVID Limitations

• The specific programming choices made by
  investigators and available pacemakers could have
  affected the results, e.g.
• Choice of DDDR pacing rate of 70
• Choice of AV interval
• DDDR devices did not have algorithms to promote
  intrinsic conduction (reduce ventricular pacing)
• Results may not apply to patients with a normal
  ejection fraction or with standard pacing
  indications.

Wilkoff B, et al. JAMA. 2002 288 3115-3123.