Program Tweak Cuts ICD Pacing/Shocks in Broad Population: ADVANCE 3

May 08, 2013

CHICAGO, IL — Implantable-cardioverter defibrillators (ICDs) programmed with prolonged detection intervals cut the total number of delivered therapies in patients with either primary- or secondary-prevention devices in a large randomized trial[1].

Less antitachycardia pacing (ATP), rather than fewer shocks, seemed to account for most of the reduction in delivered therapy in the study, the third Avoid Delivering Therapies for Nonsustained Arrhythmias in ICD Patients (ADVANCE 3) trial.

The novel programming, however, was associated with significantly fewer inappropriate shocks as well as a reduction in hospitalizations over the trial’s median follow-up of 12 months, say Dr Maurizio Gasparini (Humanitas Clinical and Research Center, Rozzano, Italy) and associates in a report published in the May 8, 2013 issue of the Journal of the American Medical Association.

ADVANCE 3 to a great extent "confirms and reinforces" results of the slightly smaller Multicenter Automatic Defibrillator Implantation Trial to Reduce Inappropriate Therapy (MADIT-RIT), reported last year[2], the authors note. They point out that MADIT-RIT was limited to primary-prevention patients and, unlike ADVANCE 3, excluded those with single-chamber ICDs or atrial fibrillation. But it did show a mortality reduction associated with the programming intervention.

Despite showing no significant effect on mortality from prolonging the detection interval, ADVANCE 3 potentially broadens the applicability of delayed detection to include secondary prevention, single-chamber ICDs, and patients with AF, according to Gasparini et al.

The trial "adds important new information to the evidence base of ICD programming for prevention of ventricular arrhythmias," writes Dr Merritt H Raitt (Portland Veterans Administration Medical Center and Oregon Health and Science University) in an accompanying editorial[3].

"Regardless of whether these programming interventions lead to reduced mortality, the unequivocal reduction in ICD shocks and the reduction in hospitalization without an increase in adverse events such as syncope suggest that this programming approach should be considered for adoption in the care of patients with ICDs and clinical characteristics similar to those enrolled in these studies."

ADVANCE 3 randomized 1902 patients with first ICDs, of whom 75% were primary prevention and 25% were secondary prevention, at 94 centers in Europe, the Middle East, Russia, and Africa to have their devices programmed for prolonged (n=948) or standard (n=954) detection intervals.

The devices could be any type of ICD, with or without biventricular pacing, that was capable of delivering ATP while the capacitor builds a charge, the authors note. All were programmed to detect arrhythmias with a cycle length of <320 ms. Detection interval prolongation in 948 patients called for detection programming of 30 of 40 intervals while standard programming in 954 patients was of 18 of 24 intervals.

Incident Rate Ratio (IRR, 95% CI) for Outcomes, Long vs Standard Detection Intervals, in ADVANCE 3

End point IRR (95% CI)
Shocks or ATP 0.63 (0.51–0.78)
Shocks 0.77 (0.59–1.01)
ATP 0.58 (0.47–0.72)
Inappropriate shock 0.55 (0.36–0.85)
Hospitalization 0.81 (0.68–0.98)

ATP=antitachycardia pacing

Compared with standard detection intervals, prolonged-interval programming was associated with significantly fewer delivered shocks or ATP (the primary end point, p<0.001), less ATP (p<0.001), and fewer inappropriate shocks (p=0.008) and hospitalizations (p=0.03); a reduction in overall shocks didn't reach significance (p=0.06).

Prolonging the detection interval, compared with the standard approach, didn't have a significant effect on mortality (hazard ratio 0.87, 95% CI 0.57–1.32; p=0.50).

In his editorial, Raitt describes several possible reasons for the different mortality results in ADVANCE 3 and MADIT-RIT:

  • Neither trial was powered for mortality, so a mortality reduction could have been by chance.

  • ADVANCE 3 used a longer detection delay, probably attenuating differences between the two groups.

  • Follow-up in ADVANCE 3 was shorter, perhaps preventing detection of potential survival gains occurring later.

  • Mean LVEF was higher in ADVANCE 3, so its lower-risk patients may have been less likely to "show an increased risk of adverse effects related to ICD shocks."

The ADVANCE 3 study was funded by Medtronic. Gasparini discloses serving on advisory boards for Medtronic and Boston Scientific. Disclosures for the coauthors are listed in the paper. Raitt had no disclosures.

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