Not so very long ago, it was probably easier to win the lottery than qualify to get an implantable cardioverter-defibrillator (ICD). ICDs were considered extreme measures for the most desperate cases. As such, patients had to have survived not one but two documented episodes of sudden cardiac arrest, be drug refractory, but also be strong enough to be able to undergo a thoracotomy to implant the device. Somehow, some patients qualified and received devices!

However, the life-saving potential of ICDs was apparent to many physicians. The ICD world changed when a few committed physicians got together to develop a suite of clinical studies that would explore the implantation of this radical device into arrhythmia-rich populations. The most famous of these studies turned out to be the Multicenter Automatic Defibrillator Implantation Trial (MADIT) and MADIT II.

Both MADIT and MADIT II looked at heart attack survivors with impaired left-ventricular function. In the first MADIT trial (published in 1996), patients had to be inducible in an EP study. The study was based on the notion that potentially dangerous ventricular arrhythmias occurred more frequently in post myocardial infarction (MI) patients. A positive EP study was utilized to help further confirm the fact that the patient possessed the necessary arrhythmic substrates to sustain a ventricular arrhythmia. The ICD turned out to reduce all-cause mortality by 54% in the ICD group when compared to the control group.

But what if these same patients had not undergone the EP study? MADIT II (published in 2002) dispensed with the EP study and found ICDs still reduced the risk of all-cause mortality by 31% versus the control group (Figure 1).

While it is very tempting to view MADIT and MADIT II as two versions of the same study, they were actually set up using two different statistical designs. Thus, it is not really accurate to make head-to-head comparisons of the studies. Both showed a significant mortality benefit for ICDs. Eliminating a positive EP study was also a major step; as we know, EP studies can be difficult procedures for some patients, particularly highly symptomatic, debilitated heart failure patients.

MADIT and MADIT II prompted a new indication for ICDs and created a new word in our vocabulary: the primary prevention patient. Primary prevention patients were those who would get an ICD to prevent the first instance of sudden cardiac arrest.

This marked a huge departure from our previous appreciation of ICDs. Now an ICD could be prescribed for a prior-MI patient without documented arrhythmias and without an EP study, even if the patient was responded well to drugs. (Figure 2)

But while the MADIT studies caused physicians to re-think how to manage MI survivors, other investigators were wondering about patients who had not had a heart attack. Would ICDs confer a mortality benefit on nonischemic patients at high risk for arrhythmic activity? That question was answered by the the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) study, which enrolled patients with nonischemic dilated cardiomyopathy and a LVEF < 35% with documented evidence of arrhythmic activity. The DEFINITE patients did not have to undergo an EP study. Instead, there had to be evidence of at least 10 PVCs an hour or runs of nonsustained ventricular tachycardia (3-15 beats above the rate of 120 bpm) on Holter monitoring.