• Arrhythmias
• Cardiology Clinical Trials
• Interventional Techniques & Devices

Arthur J. Moss, MD, University of Rochester Medical Center, Rochester, New York, USA, presented findings from the Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy [MADIT-RIT; NCT00947310] that were simultaneously published in the New England Journal of Medicine [Moss AJ et al. 2012].

Inappropriate therapy delivered by implantable cardioverter-defibrillators (ICDs) is defined as ICD therapies that are triggered by nonventricular tachyarrhythmias. These errors occur frequently despite sophisticated device-related detection algorithms designed to differentiate supraventricular from ventricular tachyarrhythmias [Moss AJ et al. N Engl J Med 2012]. Activations that fail to make this distinction can have potentially life-threatening consequences [Daubert JP et al. J Am Coll Cardiol 2008].

MADIT-RIT was a global, prospective, randomized, nonblinded, 3-arm, multicenter clinical investigation performed at 98 hospital centers in the United States, Europe, Canada, Israel, and Japan from September 15, 2009, through trial termination on July 10, 2012. The study assessed specific programming features for reducing inappropriate therapy in patients with ICDs.

The primary objective was to determine whether programmed high-rate therapy (with a 2.5-second delay before the initiation of therapy at a heart rate of ≥200 beats per minute [bpm]) or delayed therapy (with a 60-second delay at 170 to 199 bpm, a 12-second delay at 200 to 249 bpm, and a 2.5-second delay at ≥250 bpm) was associated with a decrease in the number of patients with a first occurrence of inappropriate antitachycardia pacing or shocks compared with conventional programming (with a 2.5-second delay at 170 to 199 bpm and a 1.0-second delay at ≥200 bpm). The secondary endpoints were death from any cause and the first episode of syncope.

A total of 1500 patients were randomized to high-rate therapy (n=500), delayed therapy (n=486), or conventional therapy (n=514). Baseline characteristics were similar. During a mean follow-up of 1.4 years, high-rate therapy and delayed ICD therapy significantly reduced inappropriate therapy compared with conventional therapy—high-rate therapy vs conventional therapy (HR, 0.21; 95% CI, 0.13 to 0.34; p<0.001), delayed therapy vs conventional therapy (HR, 0.24; 95% CI, 0.15 to 0.40; p<0.001)—and reduced all-cause mortality (HR, 0.45; 95% CI, 0.24 to 0.85; p=0.01; HR, 0.56; 95% CI, 0.30 to 1.02; p=0.06; respectively for the same comparisons). The frequency of a first episode of syncope was similar in the 3 treatment groups: high-rate therapy (22), delayed therapy (23), and conventional therapy (23).

Compared with conventional programming, ICD therapies for tachyarrhythmias of 200 bpm or higher, or with a prolonged delay in therapy at 170 bpm or higher are associated with reductions in inappropriate therapy and all-cause mortality during long-term follow-up. Wilkoff [N Engl J Med 2012] noted in a related editorial that the value of ICD therapy is greatly influenced and in many ways determined by the programming choices made by the physician. The results of MADIT-RIT call for careful reconsideration of the previously measured effects of ICD therapy on morbidity and mortality. A patient's unnecessary exposure to painful shocks and his or her survival may depend on programming choices.

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