MADIT-RIT: What are the Takeaways for Busy Device Clinicians?

Tom Kenny
Tom Kenny

In the early days of ICD therapy, most clinicians programmed defibrillations under the motto, “Shock early.” In setting up the patient’s therapy algorithms, most clinicians preferred to err on the side of delivering therapy — and delivering it faster rather than slower. The groundbreaking MADIT trial (published in 1996) found that implantable defibrillators conferred a mortality benefit on individuals with impaired systolic function and a positive EP study — even with no history of tachyarrhythmia. What followed is a suite of landmark studies: MADIT II discovered the mortality benefit persisted even without an EP study. MADIT-CRT explored the benefits of CRT pacing in primary prevention.1 In fact, if you search the PubMed database for “MADIT,” it will return 240 results, including many peer-reviewed sub-studies and commentaries on the MADIT series by some of the biggest names in the EP world.

The latest MADIT study is MADIT-RIT, in which the RIT stands for “reduce inappropriate therapy.” Inappropriate device therapy occurs when the implantable defibrillator delivers a low- or high-voltage therapy to terminate what turns out to be a non-ventricular tachyarrhythmia, such as atrial fibrillation with a rapid ventricular response. A substudy of the MADIT II trial found that 11.5% of MADIT II patients experienced at least one inappropriate shock during that trial and over 30% of all shocks delivered in that trial could be deemed inappropriate.2 Although it is common to think of inappropriate shocks as the result of suboptimal device programming, Daubert and colleagues found that atrial fibrillation accounted for 44% of all inappropriate shocks and that most programmed settings were not significantly different in patients who did and did not receive inappropriate therapy.2 

Inappropriate shock is painful and distressing to the patient, can lead to mental health disorders, reduces quality of life, and drains device battery life. But it goes far beyond that. Inappropriate therapy can provoke serious and even potentially lethal ventricular arrhythmias.3 So how can we protect patients from inappropriate therapy? Manufacturers have offered a variety of programmable parameters and special algorithms aimed at improving device specificity (that it only delivers therapy to actual ventricular tachyarrhythmias) and sensitivity (that it never misses a ventricular tachyarrhythmia). Despite the sometimes confusing array of programmable options, inappropriate therapy delivery remains a problem.

The MADIT-RIT study randomized 1,500 primary-prevention ICD patients to one of three study groups using a proprietary device algorithm (Boston Scientific):4

  • For one test group, therapy was initiated when the heart rate ≥200 bpm with a 2.5-second delay before therapy started
  • In the other test group, therapy was delayed by 60 seconds for heart rates from 170 to 199 bpm, 12 seconds for rates 200 to 249 bpm, and 2.5 seconds for rates ≥250 bpm
  • The “conventional group,” which acted as a control group, had a 2.5-second delay for rates of 170 to 199 bpm and a 1.0-second delay for rates ≥200 bpm

The study was set up to determine which group had the most instances of inappropriate antitachycardia pacing or shocks and when they occurred, compared to conventional therapy. The study followed the patients on average for 1.4 years.

There was a significant reduction in first occurrence of an inappropriate therapy in both the high-rate and delayed-therapy group compared to the conventional group. Moreover, there was a significant reduction in all-cause mortality in the high-rate group compared to conventional therapy (p = 0.01) and a reduction that trended toward significance in the delayed-therapy group compared to conventional therapy (p = 0.06).

The fact that both high-rate and delayed-therapy prolonged the time before the first occurrence of inappropriate therapy suggests that both of these programming strategies can reduce the rate of inappropriate therapy. 

Of course, some therapy is appropriate and necessary. Appropriate antitachycardia pacing occurred in 8% of the high-rate, 4% of the delayed-rate, and 22% of the conventional group. Appropriate shock occurred in 5% of the high-rate, 4% of the delayed-rate, and 5% of the conventional group. These rates are not surprising.

However, inappropriate therapy occurred almost as often. Inappropriate antitachycardia therapy occurred in 4% of the high-rate, 5% of the delayed-rate, and 20% of the conventional group. Inappropriate shock occurred in 3% of the high-rate, 3% of the delayed-therapy, and 6% of the conventional group. For patients with a conventionally programmed ICD, inappropriate shock therapy occurred at a higher rate than appropriate therapy (6% vs. 5%, respectively).

Setting the high-rate cutoff at 200 bpm or delaying therapy might be perceived by some clinicians as a risky strategy. After all, if a patient had a ventricular tachycardia that never exceeded 180 bpm, there would be no therapy delivery. Even the investigators were unsure if a high cutoff rate would result in increased morbidity or mortality — but it did not. The rate of adverse events, such as syncope, was similar in all three groups, so the high cutoff rate did not even result in more cases of dizziness or lightheadedness.

From diagnostic data analysis, it seems that many MADIT-RIT patients experienced episodes of nonsustained ventricular tachycardia that terminated spontaneously. In other words, treating a too-low or short-duration episode of high-rate ventricular activity did not leave room for nonsustained episodes to resolve on their own. 

The large amount of antitachycardia therapy suggests that rhythm disorders in the range of 170 to 199 bpm are surprisingly common and device algorithms have difficulty discriminating between ventricular and atrial tachyarrhythmias in this range. The investigators noted that device diagnostics reveal that some antitachycardia pacing therapy converted supraventricular tachyarrhythmias to ventricular tachycardias, which then required shock delivery. Such shocks might appear “appropriate” but demonstrate how dangerous aggressive or totally empirical antitachycardia pacing can be. 

The high-rate and delayed-therapy groups exhibited a reduction in all-cause mortality of 44% and 55%, respectively, compared to conventional therapy. This suggests that device programming, even of antitachycardia pacing settings, can be of crucial importance.

One thing to note is that the actual number of deaths in this study was relatively small; the mortality rate was 0.12% for the conventional therapy group at 2.5 years, compared to 0.05% for the high-rate therapy and 0.09% for delayed-therapy in the same time period. The study evaluated “all-cause mortality,” which is death from any cause at all, even unrelated to the study. Most device studies use “all-cause mortality” as an endpoint rather than cardiovascular mortality, since cause of death can sometimes be complicated and disputed. Since arrhythmic deaths would be a subset of all-cause mortality, this endpoint is used in most device studies. 

MADIT-RIT demonstrated that two particular programming strategies not only reduced inappropriate therapy, but also conferred a mortality benefit. As Bruce Wilkoff points out in an editorial in the New England Journal of Medicine, these results should cause us to re-think all previous ICD studies because they may have underestimated the mortality benefits of defibrillation therapy.5

The MADIT-RIT study enrolled only primary-prevention patients. An earlier study, PainFREE Rx II, explored the overall rates of inappropriate therapy in both primary and secondary prevention patients.6 Both groups had a 15% rate of inappropriate therapy, but these were slightly more common in primary-prevention patients. Of all the arrhythmic events detected and treated by the ICD, 46% led to inappropriate therapy in primary-prevention patients compared to 34% in secondary-prevention patients. With secondary-prevention patients, clinicians have arrhythmic history to help guide programming decisions.

With what we have learned in MADIT-RIT, what can the busy device clinician take away in terms of ICD programming? The MADIT-RIT study found that high-rate and delayed-therapy were both effective in reducing inappropriate shock and mortality compared to conventional therapy. Since they are both effective, the simpler one should take precedence. Programming a cutoff rate of 200 bpm is very straightforward (and much easier to program than delayed therapy) and MADIT-RIT found it reduced both inappropriate therapy and mortality rates. Forget the old mantra, “Shock early.” Program a high VF cutoff (for example, 200 bpm) and delay the onset of the therapy — MADIT-RIT shows that this saves lives

Tom Kenny is the director of education at PrepMD in Boston, Massachusetts and is the author of the Nuts & Bolts series of books on cardiac rhythm management, including The Nuts & Bolts of Cardiac Pacing, The Nuts & Bolts of ICD Therapy, The Nuts & Bolts of Cardiac Resynchronization Therapy, and The Nuts & Bolts of Paced ECG Interpretation.

Disclosures: The author discloses an affiliation with PrepMD.

Editor’s Note: This article underwent peer review by one or more members of EP Lab Digest®’s editorial board.


  1. Moss AJ, Hall WJ, Cannom DS, et al. Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med. 2009;361:1329-1338.
  2. Daubert JP, Zareba W, Cannom DS, et al. Inappropriate implantable cardioverter-defibrillator shocks in MADIT II: frequency, mechanisms, predictors, and survival impact. J Am Coll Cardiol. 2008;51:1357-1365.
  3. Vollmann D, Luthje L, Vonhof S, Unterberg C. Inappropriate therapy and fatal proarrhythmia by an implantable cardioverter-defibrillator. Heart Rhythm. 2005;2:307-309.
  4. Moss AJ, Schuger C, Beck CA, et al. Reduction in Inappropriate Therapy and Mortality through ICD Programming. N Engl J Med. Nov 6 2012.
  5. Wilkoff BL. Improved Programming of ICDs. N Engl J Med. Nov 6 2012.
  6. Sweeney MO, Wathen MS, Volosin K, et al. Appropriate and inappropriate ventricular therapies, quality of life, and mortality among primary and secondary prevention implantable cardioverter defibrillator patients: results from the pacing Fast VT REduces Shock ThErapies (PainFREE Rx II) Trial. Circulation. 2005;111:2898-2905.