Medical Device Daily Washington Editor

BOSTON – One of the Thursday morning sessions at Heart Rhythm 2006 was a debate on whether the medical establishment needs to further study risk stratification for patients who are candidates for implantable cardioverter defibrillators (ICDs). While a medical economist might argue that such analyses are needed to make best use of limited healthcare resources, the decision on how to advise individual patients based on such data is surely difficult for physicians to swallow.

Greg Flaker, MD, of the University of Missouri Hospital and Clinics (Columbia), whose titles there include the director of the electrophysiology lab, presented the argument that there is no further need to study risk stratification whereas Arthur Moss, MD, professor of medicine at the University of Rochester Medical Center (Rochester, New York) made the opposite case, that the established sum of existing data is not sufficient to fully address the question.

Flaker led off, stating that “secondary prevention ICD trials have demonstrated a modest mortality reduction,” and he urged the audience to “beware of subgroup” analysis, making the case that it may be dangerous to be a member of a subgroup who generates an outcome that “swims against the data.”

Moss proposed that risk stratification for those with ejection fractions (EFs) less than 30% is still needed, given the downward trend in incremental cost effectiveness for this patient sub-population with demonstrated co-morbidities. Referring to the MADIT II (Multicenter Automatic Defibrillator Implantation II) trial, he said that for those with EFs lower than 30%, the three-year non-ICD mortality rate was shown to be 31% and the ICD mortality rate over the same span for the same population was 22%. He concluded that the reduction in mortality was likely to be on the order of 9% and stated that a reasonable inference was that surgeons had to implant 11 ICDs in order to save the equivalent of one life-year.

Moss presented data that further suggested that “the cost per life-year saved is $235,000” in the three years covered by the MADIT II trial, but that any figures beyond those three years had to be generated by extrapolation and conjecture. He suggested that the mortality rate of 45% over three years in patients with two risk factors was a compelling case for continued risk stratification.

The MADIT II trial, in which Moss participated, was designed in part to examine how patients on conventional drug therapy fared in contrast to those on ICDs and drug therapy, and the Data Safety and Monitoring Board halted enrollment in November 2001 due to the reduced risk of death in patients involved in the study. However, those on ICDs also experienced higher rates of new heart failure and more exacerbated existing heart failure. Moss closed his presentation by insisting that stratification leads to better efficacy and lower systemic cost.

In a brief rebuttal discussion, Flaker insisted that Moss' data was “unsound” because of the inference that age was more decisive than “physiological data,” and Moss replied that MADIT II did not employ an age cut-off for enrollment. However, in support of his thesis that stratification makes sense, he noted that he found it “paradoxical” that “those younger than 60 got no benefit from ICDs.”

One of the Friday morning debates dealt with anti-tachycardia pacing (ATP), specifically asking whether ATP function should be programmed into all ICDs. Arguing the case for ATP inclusion was Mark Wathen, MD, the director of arrhythmia research at Vanderbilt University (Nashville, Tennessee), and Gust Bardy, MD, the founder of the Seattle Institute for Cardiac Research (Seattle), made the opposite case.

Wathen led off with the caveat that ICDs are installed to abort cardiac death and that “anything beyond this function has to be considered carefully.” He suggested that the debate is really about whether ATP programming should provide the first line of therapy in advance of full cardiac shock, a subject that moderator Emile Daoud, MD, assistant professor at Riverside Methodist Hospital (Columbus, Ohio), admitted he was not aware was the subject of this much controversy.

Wathen noted that traditional shock is the gold standard, effectively treating more than 99% of cases of ventricular fibrillation and 87% to 97% of cases of ventricular tachycardia. He also took ventricular flutter off the table in this discussion as ATP is not effective in dealing with this state of affairs. Wathen insisted that mortality issues do not plague ATP because no available data ascribes death directly to ATP.

Citing data from the Pain Free Rx II (Pacing Reduces Shocks for Fast Ventricular Tachycardia II) trial, for which he was the lead investigator, Wathen said that the risk of sudden death was essentially the same in both arms, each of which lost two patients (out of a total enrollment of more than 600 randomized subjects).

Some of the concerns about the use of ATP revolve around the prospect that it could fail to restore normal rhythm and delay a restorative shock. However, Wathen said that available data showed that the success rate of shock was identical with and without prior ATP. He further made the case that ATP “is the superior therapy” in part because it reduces the pain experienced by patients. However, ATP did cut down on the shock events for fast ventricular tachycardia (fast VT), reducing shocks from 67% in the control arm to 20% in the treatment arm of the Pain Free Rx II study.

Bardy's opening salvo consisted of the assertion that the “use of surrogates” can be misleading. He pointed out that cardiologists typically do not know what killed most of their patients, partly because most ICDs are not extracted from the deceased and returned to the clinician.

Bardy decried the “rampant presumption” in the medical establishment that a faster response to cardiac events is necessarily better, pointing out that the apparent lag in response time by the traditional ICD shock cycle, much of which is incurred in charging, is useful because it allows many transient events to pass without needless shock.

He added that this delay also allows data collection, but said that with the inclusion of ATP function into ICDs, “by definition, you've turned [the defibrillator] into a hair trigger.”

Bardy cited the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) results, which were published in The New England Journal of Medicinein January 2005. The general finding from this trial was that ICD therapy cut down on all-cause mortality by 23% compared to placebo, and Bardy said that the trial employed “a dumb old shockbox” in a trial that reduced decision-making by electrophysiologists. “The whim of obliterating every abnormality will only get you into trouble,” he insisted.

Bardy pointed out that nearly three of four in the Pain Free Rx I trial needed a shock, and described many of the numbers presented by Wathen as “inappropriate statistics” derived from a “fishing exercise.” He concluded that ATP should be reserved “for the frequent flier.”

In the rebuttal discussion, Wathen admitted that “we are overtreating grossly,” but made the case that ATP reduces shocks and can increase the therapeutic value because it reacts more quickly than the typical ICD shock function.

In his rebuttal, Bardy said that “it really bothers me” that the total number of deaths (most of which were not attributed to ATP therapy) in the ATP arm in Pain Free II far outstripped the number of deaths in the control group 32 to 24. He compared the fatality data to the Vioxx problems, asking where the Medical Data Safety Board was during the conduct of this trial.