Patients whose implantable cardioverter-defibrillators (ICDs) were programmed to provide high-rate or delayed therapy were less likely to receive inappropriate shocks compared with conventional programming, according to MADIT-RIT results. The two approaches also offered survival benefits.
Researchers presented the results of the late-breaking clinical trial Nov. 6 at the American Heart Association scientific sessions in Los Angeles. Their findings were simultaneously published in the New England Journal of Medicine.
In MADIT-II (Multicenter Automatic Defibrillator Implantation Trial II), researchers reported a significant reduction in the risk of death with primary ICD therapy that persisted long term (Circulation 2010;28;122:1265-1271). But MADIT-II investigators also found that one or more inappropriate shocks occurred in 11.5 percent of patients in the study (J Am Coll Cardiol 2008;51:1357-1365).
Arthur J. Moss, MD, of the University of Rochester Medical Center in Rochester, New York, and colleagues designed the MADIT-RIT (Reduce Inappropriate Therapy) trial to evaluate whether changing programming features would reduce inappropriate therapy in patients implanted with ICDs (Boston Scientific). Patients were randomized to one of three groups: High-rate, delayed or conventional therapy.
They enrolled 1,500 patients between September 2009 and October 2011 from 98 hospitals in the U.S., Canada, Europe, Israel and Japan. All patients were 21 years or older and had ischemic or nonischemic heart disease. Baseline characteristics were similar in all groups, and patients were followed for an average of 1.4 years.
Device programming for conventional therapy (514 patients) used two detection zones: one at a heart rate of 170 to 199 beats per minute for ventricular tachycardia with a 2.5-second delay before initiation of therapy and a second zone at 200 beats per minute with a one-second delay.
In the high-rate group (500 patients), the therapy zone began at 200 beats per minute with a 2.5-second monitoring delay. The delayed therapy (486 patients) approach used three detection zones: at 170 to 199 beats per minute with a 60-second delay; at 200 beats per minute with a 12-second delay; and at 250 beats per minute or higher with a 2.5-second delay.
In all patient groups, antitachycardia pacing was followed by shock therapy if pacing did not terminate the detected tachyarrhythmia. The primary endpoint was the first occurrence of inappropriate therapy. The secondary endpoints were death from any cause and the first episode of syncope.
In the conventional-therapy group, patients had a 29 percent probability of inappropriate therapy at 2.5 years compared with rates of 6 percent in the high-rate and delayed-therapy groups. The high-rate group had a 79 percent reduction in risk of a first occurrence of inappropriate therapy compared with the conventional therapy group. The delayed-therapy group had a 76 percent risk reduction compared with conventional therapy.
A total of 34 patients died in the conventional therapy group compared with 16 and 21 in the high-rate and delayed-therapy groups, respectively. All-cause mortality was reduced by 55 percent in the high-rate group and 44 percent in the delayed-therapy group compared with conventional therapy.
“In the design of the trial, we were concerned that the higher rate threshold or longer delay before initiation of device-delivered therapy might be associated with modest increases in mortality and syncope, but these concerns were not realized,” Moss and colleagues wrote. “Rather, all-cause mortality was significantly reduced with the high rate threshold of 200 beats per minute, and the frequency of syncope was similar in all three treatment groups.”
The authors wrote that the high rate of inappropriate pacing with conventional therapy reflected the inability of device algorithms to discriminate between atrial and ventricular tachyarrhythmias in the 170 to 199 beats per minute range. “In addition, appropriate anti-tachycardia pacing was significantly less frequent in the high-rate and delayed-therapy groups than in the conventional-therapy group, a finding that suggests that many episodes of nonsustained ventricular tachycardia that would have terminated spontaneously were treated prematurely in the conventional-therapy group. In retrospect, such therapy could be considered unnecessary.”
The authors suggested that the survival benefits seen in the high-rate and delayed-therapy approaches might be related to less myocardial damage from inappropriate shocks. But they added that the number of deaths in the study was small and more research is warranted.
Both the high-rate and delayed-therapy approaches proved superior to conventional therapy, they wrote, but they added that programming for the high-rate method was simple while programming for delayed-therapy method was complex.
Bruce L. Wilkoff, MD, of the Cleveland Clinic, emphasized in an accompanying NEJM editorial that the value of ICD therapy depends not only on the patient population and successful implantation but also device programming. Physicians should consider MADIT-RIT results in their programming choices, he wrote.
“Instead of favoring quick detection and therapy, physicians should adhere to the guiding principle of waiting for certainty of detection before implementing therapy,” Wilkoff advised. “This principle will result in systematic underdetection of some important arrhythmias but will also systematically reduce overall morbidity and improve survival, as shown by Moss et al.”
Boston Scientific of Natick, Mass., funded the trial.