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New trial aims to elucidate ICD, CRT-D performance in women
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Much research has been done on the benefits of implantable cardioverter defibrillators and cardiac resynchronization therapy defibrillators, but little is known about how well they perform in women compared with men and in patients with nonischemic cardiomyopathy compared with ischemic cardiomyopathy.
In fact, women have been historically underrepresented in trials of implantable cardiac devices, never comprising more than 30% of a prospective trial population.
To address that, Biotronik announced it will launch the BIO-LIBRA study, which will include only patients with nonischemic cardiomyopathy and an ICD or CRT-D, and whose cohort is expected to be at least 40% women.
Valentina Kutyifa, MD, PhD, FESC, associate professor of medicine at the University of Rochester Medical Center School of Medicine and Dentistry, and principal investigator for the trial, spoke to Cardiology Today about why women have been underrepresented in ICD and CRT-D trials and how the study might more light on the performances of these devices in women and in patients with nonischemic cardiomyopathy.
Question: Why do you think women are underrepresented in trials of implantable cardiac devices?
Answer: It has previously been shown that women often present with a different manifestation of heart disease compared with men. Women more often have nonischemic cardiomyopathy, which does not also manifest itself as CHD. In many cases, women are diagnosed with heart disease at a later age compared with men. This different pathophysiology may be one of the reasons why they are generally underrepresented in cardiology clinical trials.
There has also been data suggesting women may be less likely to participate in clinical trials in part due to family responsibilities and obligations. Also, they sometimes need more time and multiple consults to make the decision to participate in a clinical trial.
Q: Currently, what do we know about how implantable cardiac devices work in women compared with men?
A: We have information that there may be differences, but unfortunately, all the information we have at this time is limited by the relatively small number of women in previous clinical trials. There is some indication that CRT devices might work better in women, but on the other hand, there are data suggesting that an ICD alone has less beneficial effect in women compared with men. But again, we cannot draw definitive conclusions because of the small number of women in previous studies.
Q: Why did you and your colleagues decide to conduct the BIO-LIBRA trial?
A: We understood that we had very little information available on the efficacy of ICD and CRT devices in women with nonischemic cardiomyopathy. There was also a recent study, DANISH (Køber L, et al. N Engl J Med. 2016;doi10.1056/NEJMoa1608029), which suggested that maybe ICDs are not helpful at all in patients with nonischemic cardiomyopathy, and this might be especially relevant in women. So we have launched a prospective clinical study focusing only on patients with nonischemic cardiomyopathy, and especially focusing on differences in outcome by sex.
We set out to enroll at least 40% women in our patient population. This way, we will be able to provide solid information on outcomes by sex. This will be the highest proportion of women ever enrolled in a clinical study of implantable cardiac devices. Previous clinical studies had 16% to 30% women enrolled. That is much less than we need to understand outcomes by sex.
Q: Are there any devices designed specifically for nonischemic cardiomyopathy?
A: At this time, all devices are the same for men and women and for ischemic and nonischemic cardiomyopathy. We need to better understand how these devices work in men and in women, and potentially in the far future some modifications could be made based on sex if necessary.
Q: What are the endpoints that will be evaluated?
A: Endpoints include ventricular arrhythmia events and death. We will also look at the causes of death in this population. It is important with these devices to know the burden of ventricular arrhythmias, which is a surrogate for sudden cardiac death. The patients will be followed up to 3 years. They will be followed in-clinic every year, but at every 6 months, there will be a home monitoring visit. The patients will have a home monitoring device tracking them all the time so we can be sure we do not miss any ventricular arrhythmia events. While remote monitoring has become more common, it is still unique to use it in a clinical trial.
Q: Are there any exclusion criteria of note?
A: There are two major exclusion criteria. We will exclude patients with ischemic cardiomyopathy, ie, patients with significant CAD. That is a different etiology of cardiomyopathy. Also, we will exclude patients with a prior ventricular tachycardia (VT) or ventricular fibrillation (VF) event. This study will include only patients with a primary prevention ICD indication.
Q: At the end of the trial, what will you hope to have learned?
A: Right now, we don’t have information on VT/VF events in U.S. patients with nonischemic cardiomyopathy. The only such data are from the DANISH trial, which was conducted in Europe. This will be the first prospective study on U.S. soil on the rate of VT/VF events in patients with nonischemic cardiomyopathy and an ICD or CRT-D in a long time. The last one, SCD-HeFT, which included patients with both types of cardiomyopathy, was in 2005 (Bardy GH, et al. N Engl J Med. 2005;doi:10.1056/NEJMoa043399). Since then, the only U.S. data we have had comes from the American College of Cardiology’s National Cardiovascular Data Registry, but that does not report on VT/VF, only on death.
Therefore, we hope this study fills an important knowledge gap to help clinicians better understand the outcomes of this cohort, and treat these patients better.
Q: What else is unique about this study?
A: This study is also endorsed by the Electrophysiologist International Community (EPIC) Alliance, a global network for women electrophysiologists. The study will have 50 sites in the U.S., and a significant proportion of them will have a female electrophysiologist as the principal investigator. So, this is a study where women are coming together to help understand women’s and men’s health and change their outcomes for the better. – by Erik Swain
For more information:
Valentina Kutyifa, MD, PhD, FESC, can be reached at valentina.kutyifa@heart.rochester.edu.
Disclosure: The study is being funded by Biotronik. Kutyifa reports she receives research grants from Biotronik, Boston Scientific and Zoll and consultant fees from Biotronik and Zoll.