Making Headway in Heart Failure
Melissa Walton-Shirley, MD: Hi. I am Dr. Melissa Walton-Shirley, and we are sitting down today with Dr. Clyde Yancy from Northwestern University. We are going to talk about heart failure.
Dr. Yancy, let's start with TOPCAT. It has been a major topic of discussion. To recap, this study had more than 3000 patients with more than 3 years of follow-up, patient age > 50 years, with ejection fractions ≥ 45%. It looked at aldosterone antagonism in heart failure with preserved ejection fraction (HFpEF), which seems to be the elusive diagnosis that we can't do much for. Because there was no mortality benefit, are we making any real headway in the treatment of diastolic dysfunction?
TOPCAT: An Informative Trial
Clyde W. Yancy, MD, MSc: First, I want to thank you for taking an interest in heart failure. We have had discussions over the years and have deliberated on all the different trials and tried to understand where the data have taken us. I am delighted that you have seen this as a topic of interest, because it is of interest.
Let's get to TOPCAT right way. This is an important study. For the moment, let's set aside whether it was positive or negative. Instead, let's think about it as something that gives us more information. One of the principal investigators appropriately described it as "informative."
We should get out of this binary mode of interpreting clinical trials. If it's negative, we dismiss it, and move on; if it's positive, we embrace it, and incorporate it into guidelines as soon as possible.
There is another dimension here. Does the trial teach us something? Does it inform decision-making? Does it help the clinician or the investigator know more about the patient or the treatment? From that point of view, let's correctly profile this as an informative trial.
Let's talk about the patients in the study. You are correct that these patients are older. They have preserved ejection fractions, but the cut-point was at 45%. I know that you are still in the catheterization laboratory. You know that when you see a ventricle that is at 45%, that is systolic and diastolic dysfunction, and when you see a ventricle at 55%, that is probably just diastolic dysfunction. By definition, this is a heterogeneous group of patients.
The other thing to consider is that the enrollment criteria for patients were simple. Did they have a heart failure hospitalization in the preceding 12 months, or did they have an elevated B-type natriuretic peptide (BNP) level (and the threshold was pretty low: a BNP ≥ 100 pg/mL or an NT-proBNP ≥ 380 pg/mL)? [Editor's note: The speaker meant to say "≥ 360 pg/mL."]
Now pause for a moment and think on what we are talking about. A previous hospitalization or a mildly elevated BNP level was sufficient to get you in the trial. About 28% were in stratum 2, with the natriuretic peptide criterion; the others were with the previous hospitalization criterion. You have the known issues of comorbidities associated with HFpEF (hypertension, atrial fibrillation, renal insufficiency, diabetes, obesity, and sleep apnea), but you also have this mix of left ventricular function phenotypes, and then you have this natriuretic peptide, so it was a very heterogeneous group. It is important that we start from that point.
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Cite this: Dr. Clyde Yancy on Recent Heart Failure Studies - Medscape - Feb 24, 2014.