Ileana L. Piña, MD, MPH


July 30, 2014

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Hello. I'm Ileana Piña, Associate Chief of Cardiology at Albert Einstein College of Medicine in Montefiore here in New York. I am very excited today because we have just published a paper in JAMA Internal Medicine.[1]

Many of you who follow my blog know that I also work for the US Food and Drug Administration (FDA) in the Center for Devices and Radiological Health. We have been asking questions for a while about the differences in some clinical trials between women and men, specifically in cardac resynchronization therapy (CRT). CRT is the ability to synchronize ventricles that have become desynchronous because of disease. When we look at the EKG and look at the QRS, we commonly see a left bundle branch block, which is a sign of desynchrony (although not in all patients).

At the FDA, we often get premarket approvals (PMAs) to release a device. We put together 3 different PMAs, from 3 totally different trials that looked at a very similar population of class II-III heart failure patients. These patients were perhaps not as sick as in some of the earlier trials, such as MIRACLE-ICD[2] or COMPANION,[3] which had patients who were primarily class III and IV and still symptomatic despite good medical therapy. Good medical therapy still needs to be there at all levels and all stages of heart failure care, including stage B, C, and D, with stage A being more of the prevention stage.

We took all 3 of these to some very able statisticians. The lead author has tremendous statistical knowledge, and our senior author, David Strauss, has been working with the FDA and many of us through grants from the Office of Women's Health (yes, we have an Office of Women's Health within the FDA).

CRT has reduced hospitalizations and mortality as a combined endpoint in these very sick patients. The 3 trials that we looked at were MADIT-CRT,[4] REVERSE,[5] and RAFT.[6] All 3 are different, separate trials but were combined into a very elegant meta-analysis.

A couple of years ago, when we spoke about MADIT-CRT, we already noticed that the women seemed to do better, and in our HF-ACTION Trial,[7] more women than men had left bundle branch block. So there may even be a difference in the prevalence of left bundle branch block in women with heart failure vs men, and our observations were correct. The women derived a statistically significant benefit of reduction in hospitalization and mortality and in mortality alone. Guess what? It happens at a smaller QRS than the level that we now consider in the guidelines (a QRS ≥ 150 ms). This was occurring at a QRS of 129-139 ms.

I leave you with a very important message. Pay attention to the women patients that you have in your clinic. Pay attention to the women with heart failure who have a left bundle branch block; get them well medicated; and consider the use of CRT in women, perhaps even earlier than in men.

This also brings something to the forefront. We couldn't get more definitive data from one trial because we don't enroll enough women in trials. Clinicians, please get your women patients interested in clinical trials. Very often, women are a little bit scared and want to talk to their families about the trial, and the families may not want the woman in the trial because they fear that they are being used as guinea pigs. We need extensive education about the benefit that patients derive from being in clinical trials, where they are watched so carefully and they are so well taken care of. We often see patients actually do better in clinical trials than we expect them to, but it really marks the need for more women in trials. We can't just extrapolate all our results that are done primarily in men clearly to women, and this is a perfect example of where differences exist.

This is Ileana Piña signing off.


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