Prophylactic ICDs may not benefit women…

The heart of a woman may be much different than that of a man.

The “Go Red” campaign would surely agree.  As would most masters of the obvious.

But in the case of whether female hearts garner the same benefit from a prophylactic implantable defibrillator (ICD), women may be much different than men.

As published in the increasingly influential journal, Heart Rhythm, researchers from Italy and Austin TX. have published a provocative report (e-version is free) on the gender differences of ICD benefits.  The trial was a systematic review and meta-analysis of the major prophylactic ICD trials.  By culling the 5 major ICD primary prevention trials, a cohort of 1,630 women (23% of the total study populations) was analyzed.

This statistical analysis of the five major primary prevention ICD trials (the trials which current ICD implantation guidelines are based upon) revealed three very important findings:

• Women had the same mortality rate as men.  
• Women received fewer appropriate ICD shocks than men.
• Prophylactic ICDs did not confer a survival benefit in women

Shocking news!

Background:

Compared to patients with normal hearts, patients with significant heart muscle weakness are at substantially higher risk of sudden cardiac death from an arrhythmia.  Primary prevention (implantation before any cardiac event) ICD trials have shown that mortality can be statistically reduced by implanting an ICD.  These trials formed the basis for ICD implantation guidelines.  And these guidelines have resulted in a marked increase in the use of ICDs.

Although widely accepted as truisms in the death-is-failure culture of the cardiology community, these ICD guidelines have critics.  An extremely important, but infrequently cited critical appraisal of the ICD is here.  This sobering criticism of the ICD is a must read for cardiology fellows, cardiologists and arrhythmia specialists.

The real-life dilemma in applying ICD therapy is in the generalization of the clinical trials to patients.  In the primary prevention trials, the study cohorts were relatively young and for the most part, heart disease was their most life-threatening problem.  So it is easy to understand that a device that could prevent sudden death will positively impact overall death rates.  But in real-life medical practice, this is the exception rather than the rule.

In other words, a defibrillator can only prevent death from a sudden arrhythmia, but there are many other ways to die.  If one’s risk of dying of “other ways” is significant, like in a elderly patient with other non-cardiac problems, the small reduction in sudden death from an ICD would not be significant overall.  An even more disastrous situation is that an ICD might simply trade a sudden painless death for a much more unpleasant and drawn out death. (A lesson I hear frequently from my palliative care doctor and wife is that sudden death is infinitely more desirable than almost any other means of dying.)

Is this data real?

I believe this data is compelling for a number of reasons.  First, although meta-analysis trials have significant limitations, this study used only data from large-scale, prospective randomized trials.  Registries and less rigorous trials were excluded.  Secondly, the findings make sense.

Why would women benefit from a prophylactic ICD less than men?

• Women who present with heart muscle weakness, more often than men, have non-ischemic cardiomyopathy (heart disease not related to coronary obstructions.)  Undoubtedly, compared with ischemic heart disease, non-ishemic disease confers less sudden death risk.  Less arrhythmia risk means less benefit of an ICD. 
• Additionally, women enrolled in these trials were older and had more non-cardiac disease.  Being older and sicker means there are more competing causes of death.  Again, other causes of death means that an ICD is less likely to lower overall death rate.
• Women may have different susceptibilities to arrhythmia.  Take the long QT dogma that women are more likely to initially present with symptoms, while men are more likely to present with sudden death. 

Significance of the findings:

The researchers, and I, are not saying that ICDs are useless in women.  For example, I still strongly believe that in a otherwise healthy female patient with a low-EF, prior MI and wide QRS, an ICD will lower mortality.  However, this post hoc analysis of the major primary prevention trials strongly suggests that when the female cohort of the major ICD trials is considered as a whole, a prophylactic ICD did not confer a survival advantage.

This notion further challenges the present guidelines for ICD implantation, and speaks loudly for enhanced critical appraisal of the overly simplistic, ejection-fraction based ICD guidelines.  And this news further complicates the decision making process of electrophysiologists charged with applying this very expensive, invasive and emotionally-charged therapeutic tool.

Herein lies even more evidence that patients are best treated by thinking doctors rather than mandated protocols.

JMM

Addendum:

So-called meta-analysis are often highly criticized. But in this case there were few other options, as in each of the five major trials women were underrepresented.  Therefore, taken individually, none of the trials were sufficiently powered to make specific conclusions on the female cohort. The only way to consider the impact of ICD therapy in women was to cull the data of many similar trials.