Studies have started tackling the cardiac damage that can occur with certain cancer treatments. But how to evaluate cardioprotection in this application isn't always straightforward. In this video, two leaders in the field of cardio-oncology discuss the issue in the context of recent trials.
Following is a transcript of their remarks:
Javid Moslehi, MD, Vanderbilt School of Medicine, Nashville: Another exciting area is cardioprotection. Dr. Scherrer-Crosbie, can you provide us what is new at ACC on cardioprotection?
Marielle Scherrer-Crosbie, MD, PhD, University of Pennsylvania, Philadelphia: Absolutely and it's a big topic in cardio-oncology. As you know, there's a lot of work that's been going into that. What's new at ACC: There's two late-breaking trials that have been presented at this ACC and that represent efforts to validate the cardioprotective properties of lisinopril, so an ACE inhibitor, and carvedilol, a beta blocker. Another group has been trying to validate whether carvedilol alone was, in a large cohort of patients, protective of cardiotoxicity.
I'll briefly report those two trials. I thought they were really interesting. There have been a series of trials looking at, actually, similar compounds, but they were smaller trials, and they showed some effect on the prevention of a decrease in LVEF, because that's what has been measured.
Moslehi: Give me, in a nutshell, are these drugs effective or are we kind of wasting our time thinking of adding patients in on these unnecessary drugs?
Scherrer-Crosbie: The trial that looked at the prevention by lisinopril or carvedilol was done in patients with breast cancer treated by anthracycline and trastuzumab [Herceptin]. It seems like it's very hard to show an effect on trastuzumab alone of any drug, because the cardiotoxicity rate is so low. You have to define cardiotoxicity on top of that, which in that particular trial, which the lead author is Maya Guglin, included about 468 patients. The definition of cardiotoxicity was a decrease of 10% of LVEF. So is a decrease of 10% of LVEF really significant is another question.
Moslehi: Yeah, let me ask you that. What if your EF goes from 70% to 55%, which we know is normal? That's a 15% drop in EF. Why should I care about that as a cardiologist or an oncologist in a scenario where the patient is getting lifesaving cancer therapy?
Scherrer-Crosbie: That's an excellent question, and there is no clear answer to that. The 70% to 55%, as you know, 55% is in a bit of a gray zone, so we should start to worry about it. More to the point would be 70% to, say, 60% and that, really, we don't know what to do with that. But anyway, those were the criteria and these investigators did show a protective effect in the decrease of LVEF. The other part of it was a decrease of more than 5% to less than the lower limits of normal, which seems to be really significant, also. They did show an effect of lisinopril and of carvedilol in patients who had anthracyclines and trastuzumab.
The other study that comes from Brazil looked prospectively at 200 patients, but these patients had HER2-negative cancer, and so they only had anthracyclines. They didn't have anthracyclines and trastuzumab, so less of a cardiotoxic rate, if you will. They did not show any effect of carvedilol in that population. Now I do want to point out that the field of cardioprotection is bigger and that there's, for example, trials looking at the effects of statin and we are one of the groups looking at that, actually, but there [is] another group by Greg Hundley looking at the effects of statins, and so those results are still pending. Then there are other trials looking at other cardioprotective drugs, so it's really a field in great development.
Moslehi: This is really exciting, because I think there's going to be a lot coming in this area, so thanks for sharing this information.
Scherrer-Crosbie: My pleasure.