Q&A on Heart Failure Prevention, with Javed Butler, MD

Javed Butler, MD

Few, if any, conditions have captured the attention of a specialty and primary care in the same manner as heart failure has in recent years. While the fight against cardiovascular disease in the US has been a story of progress, speed bumps and roadblocks have slowed the fight. Heart failure is often at the center of conversations around the stalled progress.

With this in mind, prevention of heart failure has taken center stage for many in cardiology, primary care, and, in recent years, endocrinology. The American Society for Preventive Cardiology’s 2021 Virtual Summit (ASPC 2021) was no different, with Javed Butler, MD, MPH, Professor and Chairman of the Department of Medicine at the University of Mississippi Medical Center, leading a session on the prevention of heart failure.

To learn more about his presentation, the roles of cardiologists and primary care in prevention, and how new agents impact prevention in different risk groups, Practical Cardiology reached out to Butler and a transcript of that conversation can be found below.

Q&A on Heart Failure Prevention with Javed Butler, MD

PC: Could you take me through what were the main points of your ASPC session? And how important is the topic of preventing heart failure as we move forward in our battle against it?

JB: So, let me give a little bit of historical background. From the 1970s, the Framingham Heart Study and the lipid revolution, we have been thinking about prevention of vascular disease. For a long time, we have Framingham risk score, we have all sorts of ways to identify the risk of atherosclerotic cardiovascular disease and focused on what do we need to do to prevent atherosclerotic cardiovascular disease at all levels, primordial, primary, secondary, and tertiary prevention. These initially started with heart attack, but then it's brought into all coronary diseases, and then stroke, and then peripheral vascular disease, but it was all vascular disease.

For heart failure, the general idea was two things. First, heart failure is largely a consequence of vascular disease. So, you don't need to focus on heart failure because if you're preventing vascular disease you were preventing a heart failure anyway. Second, there is nothing specific about heart failure because whatever you're going to do for vascular disease prevention are the very same overlapping risk factors to heart failure.

So, it was like really sort of ignored and sort put on the side. None of these risk prediction models or clinical trials had heart failure as a primary point.

I think we have evolved from that point. Now, we do know that a sizeable minority, about 40%, of patients who develop heart failure, do not have manifest atherosclerotic cardiovascular disease. Now, we obviously have not done caths on everybody—that's not how we practice medicine. So, a large minority of patients with heart failure have no manifest atherosclerotic cardiovascular disease and, in some higher risk patients like patients with diabetes or chronic kidney disease, that proportion is even higher; and some data that may suggest that it may actually be a majority at more than 50%.

The third thing is that the traditional heart attack or later heart failure has been heart failure with reduced ejection fraction (HFrEF). For heart failure with preserved ejection fraction (HFpEF) is the more dominant form of heart failure in older people whose proportion is increasing as the population ages and among those with high-risk diseases like diabetes or chronic kidney disease.

Lastly, we know not only are the generic therapies like smoking cessation, Life's Simple 7, exercise, and healthy living and smoking, those things are good, but hypertension has just dramatic improvement in heart failure. I mean, you control blood pressure, you knock it out by 50% and even trials that have not shown a remarkable improvement in stroke and AMI with blood pressure control, we still see a 50% reduction in heart failure, including in atherogenic areas. Now, with these SGLT2 inhibitors, we have this specific drug for primary prevention of heart failure, even if heart attack or stroke risk is not altered. So, we have specific guarantees as well. I think if you put all of these things together, we are at a point where heart failure prevention should get some air.

PC: With so many patients presenting without the historic, traditional risk factors, how do you go about identifying these patients?

JB: The first of the risk prediction models that came out was from the Framingham investigators, about 30 years ago, which may not be necessarily very practical for clinical use, because they had things like pulmonary function tests, or albumin and others. Subsequently, the Health ABC group, the Healthy Aging, and Body Composition group from NIA, had their prediction model, but at this point, there are five or six different clinical risk scores out there that do not require anything sort of high-tech and you can grade the risk of development of heart failure.

Honestly, just simply check using simple natriuretic peptide tests and that can give you a very good idea about higher risk for heart failure patients or undiagnosed heart failure patients and who to do an echocardiogram.

So, this is where it starts to get technical. For instance, with SGLT2 inhibitors, we know that if you look at heart failure risk, the benefit of heart failure prevention is across the risk gradient from low- to high-risk patients. What we have not done is cost-effectiveness analyses. While the relative risk reduction with SGLT2 inhibitors is same across the risk profile, the absolute risk reduction varies. So, we really don't have good cost-effectiveness studies, that assess at what point screening heart failure and treating heart failure is cost effective and where it becomes cost ineffective. Sometimes, the risk is so low, that even if you reduce the risk by 15-20%, it's just not worth it to give those drugs and those kinds of studies have not done. But, at least in high risk diabetic patients, it's crystal clear that giving SGLT2 inhibitors will be very beneficial.

PC: How important will these newer agents be as we move ahead in the fight against heart failure?

JB: Now, we have five clinical trials and patients with diabetes for prevention of heart failure. So, if you look at EMPA-REG Outcomes, CANVAS, DECLARE, VERTIS-CV, and SCORED examined five different agents and in all of them, except for VERTIS, had about 80-90% of the population without heart failure at baseline. The majority in every trial did not have heart failure and you substantially reduced the risk of nuance or heart failure in those patients. We now have data on more than 30,000 patients and I think that's a special thing. The question is, do you have high risk patients without the diabetes where you can prevent heart failure with an SGLT2 inhibitor? Because we see in secondary prevention–once you have developed heart failure, whether or not you have diabetes or not—you benefit, right? So, both DAPA-HF and EMPEROR-REDUCED found diabetes has no impact.

The question is in primary prevention. If you don't have a diagnosis of heart failure and you don't have diabetes, will SGLT2 inhibitors help? We have some idea, right? So in DAPA-CKD, the half of the CKD population did not have diabetes and you prevented heart failure. There is actually some earlier suggestions that even in high-risk patients without diabetes, you can prevent heart failure. There are two studies going on now, one with empagliflozin and one with dapagliflozin in post-MI patients with or without diabetes looking at prevention of heart failure in the post-MI setting. So, I think this will continue to evolve, but at least we have some data in CKD population, that even without diabetes, you prevent heart failure.

PC: How important is the role of primary care and internal medicine in optimal heart failure prevention?

JB: Unbelievably important. I mean, we cannot survive without good primary care. Patients are referred to cardiologist either after the diagnosis is made or they have persistent symptoms and for whatever reason the diagnosis is unclear in the primary care setting. Early risk factor modification, early screening, early diagnosis, and early treatment would make it (heart failure specialists) not that important. I mean, I would love to live in a world where people are sent to heart failure doctors only for transplants and LVADs and the rest is all taken care of in primary care.

I think it's crucially important. Now, I am very sensitive. My wife is a family practice doctor. So, I completely understand. She reminds me all the time to not get too excited about yourself—we just treat one disease, they treat everything. I understand the pressures on primary care, but they will be crucially important. They are sort of the orchestra conductors, right? We are all playing our one organ with chronic kidney disease, and with heart failure, and with diabetes, but they are really the orchestra conductor. So, I think it's critical.

Editor's Note: This transcript has been edited for space and clarity.