Avoid Delivering Therapies for Nonsustained Arrhythmias in ICD Patients - ADVANCE III

Jun 11, 2014
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Medtronic Inc.
Date Updated:
06/11/2014
Original Posted Date:
06/11/2014
References

Description:

Although implantable cardioverter-defibrillators (ICDs)/cardiac resynchronization therapy-defibrillators (CRT-Ds) have a significant role in preventing sudden cardiac death (SCD) in high-risk patients, especially for secondary prevention, inappropriate ICD shocks are common (8-40%). They are associated with high morbidity as well.

Hypothesis:

Programming ICDs to increased detection intervals before therapy administration would be safe and efficacious as compared with conventional programming.

Study Design

  • Placebo Controlled
  • Randomized
  • Blinded
  • Parallel

Patient Populations:

  • Age >18 years
  • Underwent their first ICD or CRT device implantation

    Number of enrollees: 1,902
    Duration of follow-up: 12 months (median)
    Mean patient age: 65 years
    Percentage female: 14%
    Ejection fraction: 30%
    New York Heart Association class: III/IV (48%)

Exclusions:

  • Previously undergone ICD implant
  • Brugada syndrome, long QT, hypertrophic cardiomyopathy, ventricular tachyarrhythmia associated with reversible cause

Primary Endpoints:

  • Total ICD therapies delivered

Secondary Endpoints:

  • Percentage reduction in the number of shocks delivered per participant to treat appropriate and inappropriate spontaneous episodes with a fast cycle length
  • Hospitalizations
  • Quality-of-life measures
  • Death
  • Arrhythmic syncope

Drug/Procedures Used:

Patients undergoing ICD implantation were randomized in a 1:1 fashion to either prolonged detection (30 of 40 intervals) or routine programming (18 of 24 intervals). All ICDs were programmed to detect arrhythmias with a cycle length of ≤320 msec. A “monitor only” ventricular tachycardia (VT) detection interval was mandatory for all patients without previous documented VT.

Concomitant Medications:

Beta-blockers (81%), angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (81%), digitalis (14%), antiarrhythmics (20%)

Principal Findings:

A total of 1,902 patients were randomized, 948 to long-interval detection and 954 to standard-interval detection at 94 centers in several countries. Baseline characteristics were fairly similar between the three arms. Approximately 41% had biventricular ICDs and 29% had single-chamber ICDs. Approximately 75% of the patients enrolled had an ICD implanted for primary prevention; only 16% had a history of prior sustained VT. A left bundle branch block morphology was noted in one third of all patients.

The primary endpoint of delivered ICD therapy was significantly lower in the long-interval detection arm as compared with the standard-interval programming arm (42 vs. 67/100 patient-years [PY]; incidence rate ratio [IRR], 0.63; 95% confidence interval [CI], 0.51-0.78; p < 0.001). This was mainly due to a significant reduction in inappropriate antitachycardia pacing (ATP) (23 vs. 37/100 PY; IRR, 0.58; 95% CI, 0.47-0.72; p < 0.001); inappropriate shocks were numerically lower (IRR, 0.77; 95% CI, 0.59-1.01; p = 0.06).

Time to first ICD therapy was similarly lower in the long-detection arm (p < 0.001). Appropriate therapies were similar between the two arms (p = 0.79). Quality-of-life scores were similar between the two arms, but hospitalizations were lower in the long-detection arm (42.1 vs. 51.7/100 PY, p = 0.03). Rates of syncope were numerically higher in the long-detection arm (3.1 vs. 1.9/100 PY, p = 0.22); overall mortality rates were similar (5.5 vs. 6.3/100 PY, p = 0.50).

On subgroup analysis, in 477 patients who received an ICD for secondary prevention, a similar reduction in the primary endpoint (IRR, 0.75; 95% CI, 0.61-0.93; p = 0.008) was observed, again driven by a reduction in both appropriate and inappropriate shocks.

Interpretation:

The results of the ADVANCE III trial indicate that programming ICDs with a longer detection interval is superior to conventional programming zone in reducing delivered ICD therapies (mostly inappropriate ATP). These results are confirmatory to those noted in the MADIT-RIT trial, in a larger, slightly more diverse patient population. A subgroup analysis indicates benefit in patients receiving ICDs for secondary prevention as well. 

However, contrary to MADIT-RIT, no difference in mortality was noted with increased delay. This could be due to differences in the length of delay between the two trials, but any potential mortality reduction will need to be confirmed in future studies.

References:

Kloppe A, Proclemer A, Arenal A, et al. Efficacy of long detection interval ICD settings in secondary prevention population: data from the ADVANCE III trial. Circulation 2014;May 16:[Epub ahead of print].

Gasparini M, Proclemer A, Klersy C, et al. Effect of long-detection interval vs standard-detection interval for implantable cardioverter-defibrillators on antitachycardia pacing and shock delivery: the ADVANCE III randomized clinical trial. JAMA 2013;309:1903-11.

Keywords: Tachycardia, Ventricular, Secondary Prevention, Syncope, Bundle-Branch Block, Hospitalization, Death, Sudden, Cardiac, Defibrillators, Implantable, Cardiac Resynchronization Therapy


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