DAVID Trial

1
DAVID Trial

• The Dual Chamber and VVI Implantable
  Defibrillator Trial
• Pacing or Ventricular Backup Pacing in Patients
  With an Implantable Defibrillator

2
DAVID Background

• ICD therapy is the 1st line therapy for
  prevention of sudden cardiac death.1,2,3,4,5,6
• Effectiveness of ICD therapy was established
  using single chamber ICDs.
• Approximately 10 of ICD patients have a Class I
  pacing indication at the time of implant.7
• Most ICDs implanted today are dual chamber.

• AVID. N Engl J Med.. 19973371576
• CIDS. Circ. 20001011297.
• CASH. Circ. 2000102748

• MADIT. N Engl J Med. 19963351933.
• MUSTT. N Engl J Med. 19993411882.
• MADIT-II. N Engl J Med. 2002346877.
• Best . PACE. 199922(1, part I)79-85.

3
DAVID Background

• Many VT/VF patients with an ICD have ventricular
  dysfunction and heart failure.
• Optimal medical therapy for LV dysfunction and
  CHF includes ACE inhibitors and beta blockers.
• Antiarrhythmic medications may also be used for
  AF or for reducing the frequency of VT/VF.
• This drug regimen may lead to chronotropic
  incompetence.

4
DAVID Background

• Dual chamber atrial based pacing could be
  beneficial by allowing for
• Optimal medical management
• Increased heart rate and cardiac output
• Reduced incidence of AF

5
DAVID 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.

6
DAVID Study Design

• Multi-center, randomized, single-blind, parallel
  2-group design
• Enrolled ICD indicated patients
• no indication for antibradycardia pacing
• LVEF ?40
• No persistent or frequent, uncontrolled AF

7
DAVID Study Design
Successful ICD Implant N 506
Single-blinded randomization to pacing mode
DDDR-70 bpm n 250
VVI - 40 bpm n 256
Follow-up to study closure every 3 months
8
DAVID Programming

• All randomized programming as per physician
  discretion except
• Tachyarrhythmia detection set at 150 bpm
• Atrial and ventricular bipolar EGMs and markers
  enabled
• SVT discrimination based on ventricular rate only
  in the VVI-40 group
• SVT enhanced discrimination ON, mode switching ON
  in the DDDR-70 group

9
DAVID HF Drug Therapy

• Optimal medical therapy for LV dysfunction and
  heart failure
• Initial and target doses for ACE-inhibitors and
  Beta Blockers defined in protocol
• ACE inhibitor if tolerated, then ARB, if ARB not
  tolerated then nitrates and hydralaxine for
  afterload reduction
• Add BB after ACE inhibitor therapy is stabilized
• Diuretics as needed
• Digoxin for NYHA Class II/III patients
• Spironelactone added if functional Class III/IV
  with above

10
DAVID Primary Endpoint

• Freedom from death or first hospitalization for
  heart failure
• Events Committee reviewed all hospitalizations
• HF hospitalization criteria
• admit to hospital for gt24 hours with worsening
  symptoms, e.g. increased functional class,
  orthopnea, dyspnea, edema.
• ?1 intensive treatments for CHF within 24 hrs of
  admit, e.g. intravenous diuretics, inotropic
  agents, placement as Status 1 on transplant list

11
DAVID Baseline Characteristics
12
DAVID Baseline Characteristics
13
DAVID Drug Therapy 6 Months Post Randomization
14
DAVID Patient Flow
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
256 VVI-40 (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
250 DDDR-70 (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
15
DAVID Follow-up

• Median 8.4 months Range
  0-23.6 months
• Time VVI-40 (n 256) DDDR-70 (n250)
• 6 months n158 n159
• 12 months n90 n76
• 18 months n25 n21

16
DAVID Results
17
DAVID Results
Death or First Hospitalization for New or
Worsened CHF
0.4
Relative Hazard (95 CI), 1.61 (1.06-2.44)
0.3
Cumulative Probability
0.2
0.1
0
0
6
12
18
Time, mo
No. at Risk DDDR VVI
250 256
159 158
76 90
21 25
18
DAVID Results
First Hospitalization for New or Worsened CHF
0.4
0.3
Relative Hazard (95 CI), 1.54 (0.97-2.46)
Cumulative Probability
0.2
0.1
0
0
6
12
18
Time, mo
No. at Risk DDDR VVI
250 256
155 156
74 89
21 24
19
DAVID Results
Death From Any Cause
0.4
0.3
Relative Hazard (95 CI), 1.61 (0.84-3.09)
Cumulative Probability
0.2
0.1
0
0
6
12
18
Time, mo
No. at Risk DDDR VVI
250 256
173 172
95 96
30 25
20
DAVID Results

• Pacing percentage and outcome in the DDDR-70
  group
• Two subgroups
• RV pacing ?40
• RV pacing 41-100
• Patients who survived to the 3-month follow-up
  visit had better 12-month event-free survival in
  the ?40 group.
• 41-100 RV Pacing 75.9
• ?40 RV Pacing 86.9

21
DAVID Discussion

• Intrinsic ventricular activation is better for
  ICD patients with left ventricular dysfunction
  who do not need pacing.
• The RV pacing imposed by the DDDR pacing mode
  appears to cause ventricular dsynchrony in ICD
  patients with existing ventricular dysfunction.
• Ventricular dsynchrony leads to worsening heart
  failure

22
DAVID Discussion

• 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 SSS 1
• 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.

23
DAVID Limitations

• The specific programming choices made by
  investigators could have affected the results,
  e.g.
• Choice of pacing rate of 70
• Choice of AV interval
• Results may not apply to patients with a normal
  ejection fraction or with pacing indications.

24
DAVID Conclusion

• Programming of pacing functions in dual chamber
  defibrillators 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.