Heart failure

SGLT2 inhibitors and GLP-1 receptor agonists in heart failure with reduced and preserved ejection fraction


Neil Minkoff, MD: How do you, as clinicians, decide when to incorporate this into a treatment journey, and at what point in the process do you integrate it if the goal is to try to prevent downstream speeds, downstream complications and the bad results? Are you doing this right now? Do you do this when the patient gets more complicated? This is one of the things payers struggle with understanding where it stands in terms of not just diabetes but CHF. [congestive heart failure] and now the metabolic syndrome.

Nihar R. Desai, MD, MPH: Going back to something you alluded to before, I would absolutely agree that cost is part of it and that access is a big part of the underuse of these therapies. The point you raised is important and needs to be underlined, that the clinical community has not come together around the data. There is a lot of clinical inertia – maybe not so much the inertia as the fragmented and siled way our system is set up, which does a disservice to all of our patients, especially the cardio-renal patient and cardiometabolic that really needs a whole team mindset and approach. .

Part of this siled and fragmented system makes cardiologists say, “We’ll let the endocrinologist write it down.” “They will say:” And the nephrologist who writes it? What about the primary care physician who writes it? Then no one writes it down and the patient finds himself 6 months, 1 year or 2 years later in the process of his illness. Maybe they had multiple hospitalizations that could have been avoided if people came together and reimagined the care in a way that provided the best care for this patient. At Yale [School of Medicine], we have a group that has come together and committed to how we navigate this complex path that we need to move forward with. How to develop a course of care for them? On the cardiovascular side for patients with heart failure, we have tried to come together and build a consensus around our faculty to say: “given the benefits that we have seen for these therapies in dedicated trials on patients with heart failure. heart failure, we have to be the ones leading this for our patients.

Whether or not the patient has diabetes, the benefit is fairly consistent. It’s overwhelming, and it’s very early. There is an early benefit to these therapies, and we started to say, “It’s up to us, and we have to stand up for our patients and offer them therapies that we think are important for their underlying disease, but do- the. in a way that is collaborative. This allows the endocrinologist to participate if there is anything else to change and to ensure that our nephrologist colleagues are on board as well, which they absolutely are. This has been a very successful path for us, and I hope it means that we are providing these therapies to patients who need them in a much faster and more standard way.

Neil Minkoff, MD: It’s pretty clear to me that the earlier adoption of CHF makes sense. Most of the data to date, however, has been in reduced discouragement for action. How do you look at patients with preserved ejection fraction and do that mental math to add that to the diet or not?

Nihar R. Desai, MD, MPH: For so long we have had these 2 worlds of heart failure: reduced EF [ejection fraction] and systolic heart failure. We have had many trials demonstrating a benefit, as well as triple therapy and now quadruple therapy. On the side of preserved EF, which probably accounts for half of heart failure patients, we didn’t have a lot of therapies available. We are managing their blood pressure, atrial fibrillation, and coronary artery disease which were probably all contributing factors, but we have never had dedicated therapy for preserved EF heart failure. Then we had a silver lining with spironolactone, and we got the FDA indication for it.

Then we learned that, given the early signals with SGLT2 inhibitors, several clinical trials in EF preserved heart failure were initiated. Although we haven’t seen the full data, it will be released to the European Society of Cardiology. [Congress]. We have seen the first results from the EMPEROR-Preserved clinical trial. Empagliflozin in a large population of patients with preserved EF had met its primary endpoint. This is another important sign that SGLT2 inhibitors may also have important effects and benefits for our patients with preserved EF. As Dr Ganda mentioned earlier, this builds on what we saw in the SOLOIST-WHF program, where there appears to be a benefit in patients regardless of ejection fraction, as patients with systolic heart failure and diastolic heart failure or preserved EF both seem to benefit. We now have the first results from EMPEROR-Preserve suggesting that we finally have evidence-based therapies for our patients with EF preserved heart failure. What a welcome change for all of us.

Neil Minkoff, MD: I’ll ask you a similar question, Dr Ganda. Approaching it from an endocrine diabetes perspective, as opposed to a cardiovascular angle, how do you decide when to add diabetes treatment and then add it to diabetes treatment? What else do you think after that, in terms of GLP1 or something like that in these patients?

Om P. Ganda, MD: To continue with what Dr Desai was saying, this was not very good news. If EMPEROR-Preserve, for example, is very positive on the front line, yes it is. There are more people with diabetes with preserved heart failure. Dr Desai can correct me, but it was a block where it was much more common in people with diabetes, but we had no definitive treatment. In our field, I don’t mean to say that GLP1 receptor agonists shouldn’t be used first. It depends on the patient. If you look at the guidelines including the ADA [American Diabetes Association] guidelines, if you don’t have a patient on GLP1 receptor agonists and blood sugar control is not good, especially in obese patients, the first thing you want to do is recommend starting before you start. intensify insulin therapy, without making it much more complex on the patient. A combination of basal insulin and GLP1 receptor agonists is an excellent therapy for diabetes.

It depends on the patient’s goal, but whatever the goal, we can simplify the diet. In the process, we also get some benefits of cardiovascular protection or perhaps stroke reduction, which have been shown more conclusively with GLP1 receptor agonists so far. We are concerned about the high risk of cardiovascular events and heart failure. The most common risk factor for heart failure is obesity, and if you combine obesity and diabetes, you have big problems. It has been shown in some large analyzes of data that for every 1% reduction in body weight – say, a 2 to 3 pound reduction in weight in a 200 pound person – obese people have a higher reduction, of about 2% to 3% of heart failure. incidents prospectively. These are very important data that we must keep in mind.

Obesity is also becoming an important factor in the progression of kidney disease, even at the beginning. Years ago, morbidly obese people were shown to suffer from proteinuria for no other reason. They still don’t have a drop in eGFR [estimated glomerular filtration rate], but they have proteinuria as the first sign of kidney dysfunction. We’ll see if there are any ongoing trials, dedicated randomized controlled trials in obese people with GLP1 receptor agonists, for example. For the first time, we have semaglutide in higher doses and tirzepatide, the new GLP1 and GIP agonists, combined in 1 tablet. It’s not yet available, but these drugs cause incredible weight loss, almost close to what we get with bariatric surgery. Someday we may use these drugs rather than sending the patient to the surgeon and increasing the rate of production costs if these tests prove positive. We will wait a few more years before we can say with certainty that the treatment of obesity will be used not only for cardiovascular disease, but also for kidney problems.

Transcription edited for clarity.


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