Medical Device Daily National Editor

BOSTON — Implantable cardioverter defibrillators (ICDs) provide shocks that prevent cardiac arrest – but what then?

It is no particular surprise that the primary emphasis concerning ICD technology coming out of last week's scientific sessions of the Heart Rhythm Society (Washington) was the ability of these devices to extend survivorship to implantees.

It is no surprise because the attendees at this conference are predominantly electrophysiologists, clinicians who make their living by implanting electronic devices, primarily pacemakers and the aforementioned ICDs, and they are unlikely to banner the risk portion of the risk/benefit equation.

Thus, one of the late-breaking trials highlighted at one of the society's press conferences for reports focused on ALTITUDE, an observational study of how long patients implanted with ICDs and the CRT-D versions of ICDs (an advanced form of the ICD) lived following implantation.

The abstract and press release about ALTITUDE made two points about its importance:

• One, its large size (just one person short of 86,000), the largest for this type of study to date.

• Two, that it is a "real-world" type of study, meaning implantations in a "naturalistic" every-day population of heart patients, rather than the carefully selected populations that characterize clinical trials – or what the press release describing the study called the "confines" of the initial pivotal trials.

The third important point made by the researchers was that the study demonstrated that the patients implanted with these devices were found to live longer, on average, than had been found with their use in early clinical trials, about 10% longer, on average.

The press statement put this added benefit as follows: "Five year survival in 47,032 patients after ICD placement, and 38,967 CRT patients, is 91.8% and 75.6% [respectively]."

These higher numbers were attributed to improved device technology, better selection of patients and "the ability to monitor device function and symptom status over a network" – this last being the LATITUDE remote monitoring system from Boston Scientific (Natick, Massachusetts) that gathered physiological data from the implantees as well as device information.

Inquiring minds, of course, should wonder about these results – with more than one or two grains of salt – since these conclusions are not saying that this therapy is being shown to be a great deal better than another form of therapy intended to prevent cardiac arrest, only that the therapy, as it is being used now, is better than this therapy as it was used a certain number of years ago.

Put more briefly: ALTITUDE is not a clinical trial of alternate therapies, via comparison of investigational and control groups, but an "observational study" of two versions of the same therapy.

However, the HRS conference, as a matter of fact, did provide a clinical trial of the regular sort, MADIT II, which compared the outcomes for patients implanted with an ICD device and those not implanted with one.

The result of this study is that, on the basis of eight-year follow-up, those implanted with the ICDs lived, on average, 1.2 years longer than those without the devices – an "all-cause mortality probability of 45% among patients with an ICD as compared to 61% among patients without an ICD."

Lead author Ilan Goldenberg, MD, of the Heart Research Follow-up Program at the University of Rochester Medical Center (Rochester, New York), praised these results (again not unexpectedly), saying that the study "proves that ICD therapy, sustained for over eight years, does in fact improve survival rates and ultimately saves lives."

(And one press report version of the study said that it showed the technology can extend life by an "entire year" – not just a year, but an "entire" year, an apparent attempt by the writer to puff up the number 1.)

But the significance of the amount of life extended by an ICD is something we can question, based on going back to ALTITUDE and one of the other findings from that study – and I highlight this: "Shock is associated with decreased survival for both ICD and CRT patients (HR = 1.60; p < .0001)."

Further, adjudication was used in this study to determine which of the shocks recorded in LATITUDE were "appropriate" and those "inappropriate" – assuming here, that an appropriate shock prevented death by cardiac arrest, while an inappropriate shock not being a specific life-saving reaction by the device.

Significantly, the adjudication ruled that 43% of the shocks were inappropriate, and 80% of these inappropriate shocks were responses to a problem arrhythmia, but not a life-threatening one.

Repeat here: inappropriate – prompting a comment in the conclusion portion of the ALTITUDE abstract that this 43% is not a large problem but rather "a significant clinical issue" needing to be addressed.

These qualifiers cast a broad shadow over any conclusion that ICDs offer a significant increase in survival (and we suggest that while an average additional 1.2 years may be added to a life and may indicate numerical significance, it doesn't necessarily convey great human significance).

It seems that what we can say about ALTITUDE is this:

• One, that those receiving "appropriate" ICD shocks avoid death by cardiac arrest but that these patients generally died sooner than implantees who received no shock from their devices.

• And two, that those receiving inappropriate shocks also died sooner than implantees receiving no shocks.

While it is difficult to put ALTITUDE and MADIT II together, these conclusions prompt considerable doubts about the findings of MADIT II and the ability of ICDs to extend survivorship.

If shocks "decrease" survival then the conclusion is that the only ones living longer in these studies are those who are implanted with ICDs that never have to perform the life-extending benefit of zapping the heart back to normal activity.

Leslie Saxon, MD, of the Keck School of Medicine at the University of Southern California (Los Angeles), who presented results of the ALTITUDE study, did note a conclusion that is hard to contradict: that shocks, whether appropriate or inappropriate, indicate that the person shocked is sicker, or is getting sicker, and that more than anything else these patients need much closer management.

So, as to the real benefits of ICDs ... the next analysis of MADIT II should answer this question, as follows:

What was the mortality of those implanted with ICDs who received the "appropriate" life-saving shocks, compared to those not implanted with these devices and receiving medical/drug therapy?

That would really tell us something about ICDs and how significant they are in extending life.