Dr. Monique Tanna and Dr. Joyce Wald discuss treatment of heart failure, incorporating SGLT2 inhibitors into heart failure management. They elaborate on the choice between LVAD and transplant, other heart failure treatment options, and more.
Related Links:Twitter @PennMDForum See Dr. Tanna’s physician profile See Dr. Wald’s physician profile Thank you so much. Everybody for joining, um, the conference today. I wanted to introduce Dr Monique Tana, who is one of our rising stars at Penn. She does a lot of our remote monitoring, um, as well, Cardia memes and does a lot for us to help us take care of our patients who are incredibly complicated. And what you put together for us was an s g l t. To guidelines on how to start them. Because I don't know about you guys. I'm petrified to start an STL t to, um and and I don't know what to do with them. So the first half of the lecture is going to be Monique, um, discussing how to incorporate SLT two inhibitors into your heart failure practice. And if we have time, I'll talk about how to incorporate mechanical secretary support into your practice. So go ahead, Monique, your slides look great. Thanks. Joyce. Um, so Good evening, everyone. Um, it's my pleasure today to talk about S e l t two inhibitors, um, and hard for your outcomes with SV lt two inhibitors as well as how uhm we've strategized to implement them in our practice. Um and I look forward to also hearing your experience, Um, and what that's been like and how many of you have been incorporating them into your practice as well. Um, so I have no financial disclosures. As Joyce mentioned, I am the, um, the, uh, for the heart failure remote monitoring program here at Penn. Um, and this I p i for some remote monitoring devices, but I won't be talking about these today. Um, so a brief outline of my talk is that we'll go through some background clinical data, um, and the trials of STL t two inhibitors and heart failure patients. Um, and then I'll spend some time on challenges, barriers and common questions that we have encountered. Um, and then I'll show some brief, some sample pathways, and I'm going to say out loud that we make this very casual. So if anybody has a question along the way, stop Monique. And don't use the chat. You can go ahead and just a new mutant. Ask a question or text me? Definitely. Um, definitely. Just feel free to stop me at any point. Um, so as you all know, there are four drugs in this category. um, currently available in the United States and magnificent counting with us in dappled with this in an article in person. Um, and the way that these work is that they inhibit the sodium glucose co transporter to, um in the proximal to view. Um, and by doing so, they reduce reabsorption of filtered glucose in the proximal tube. You and this leads to increased urinary glucose excretion, along with other effects, which I'll go into a little bit later. So in the interest of time, I'll just review the clinical data in patients with heart failure. Um, but as I'm sure you know, um, these drugs were also shown to have benefit in improving cardiovascular outcomes in patients without heart failure as well. So the first study is the Data HF study, which was published in November 2019, and this was a study of 4700 patients with N. Y H a class 2 to 4 heart failure and in a direction fraction of 40% or less. Patients are also required to have an elevated anti pro BMP level. There were a number of exclusion criteria, but some that I wanted to highlight is that patients with Type one diabetes were excluded. Patients with this is so high blood pressure of less than 90 were excluded in a G f. R of less than 30. These patients were randomized to dappled with this in 10 mg daily versus placebo, and the population in the study consisted of 42% with diabetes and the mean g fr in the study population with 66 the primary outcome was worsening heart failure or cardiovascular death, and worsening heart failure was defined as either hospitalization or an urgent visit requiring I v therapy. The median follow up period was 18 months. Um, and this is the results. So, as you can see in the first graph labelled A, there was a significant improvement in the primary outcome in patients who were prescribed a public person and the hazard ratios 0.74 There was also a significant improvement in hospitalizations for heart failure, um, death from cardiovascular causes as well as death from any cause, and you can see the hazard ratios on the graphs here. Notably, these findings were consistent and patients who had diabetes, as well as patients who did not have diabetes. So it's irrespective of whether or not patients had diabetes in terms of adverse events, they were similar between both groups. Um, specifically adverse events related to volume depletion, renal dysfunction and hypoglycemia, which are things that we worry about did not differ between the treatment groups. There were three patients in the data. Cliff isn't group who experienced DK A Um while there were none in the placebo group, um and then notably, there were no patients with four years gangrene in this study. The second study, um, is empty. Magnificent. So this is the Emperor Reduced trial, published in October of last year, and this study looked at 3730 patients again with NY AJ class 2 to 4 heart failure and also with an ejection fraction of less than or equal to 40%. Patients also had to have an elevated anti pro BNP level, Um, and similarly, in addition to other exclusion criteria, this trial also excluded patients with this is like blood pressure. Less than 100 um, a G f are less than 20 in this study, and patients with a history of ketoacidosis patients were randomized to enable Griffiths and 10 mg daily or placebo. And in this study population 50% of patients 10 diabetes the mean Jaafar was 62 similarly, the primary outcome was hospitalization for worsening heart failure or cardiovascular death and the media and follow up with 16 months. So again, you can see that the primary outcome was significantly reduced in patients treated with magnificent um, and the hazard ratio here was 0.75 And again, this outcome was consistent, regardless of whether or not patients had diabetes. You can also see in the second graf first and recurrent hospitalizations for heart failure were also significantly reduced of note. The annual rate of decline in G F. R was also slower in the empty magnificent group, Um, and subsequently what we saw in the DAPA CKD study, which I'll show you in a little bit, um that we know that these drugs also likely have improvement in renal outcomes as well. Um, of note in this trial, MPEG Lifson did not significantly decrease cardiovascular death or all cause mortality. Unlike the DAPA HF trial, where data Gibson did reduce both of those as well in terms of adverse events. Uncomplicated genital tract in fact action were more common with magnificent. Although the rates were low, Um, it was 1.7% in the patients given ample, magnificent and 0.6% in patients treated with placebo. So switching gears a little bit. Um, I want to talk about the potential mechanisms of cardiovascular benefits so we know that these drugs are beneficial both in terms of cardiovascular outcomes as well as heart failure outcomes. Um, and these are some of the ways we think that they're beneficial. Um, we know that they are glucose lowering. They can lead to weight loss. They do have a modest effect on reduction in blood pressure without increasing heart rate. We think that they decreased arterial stiffness and vascular resistance. Um, increase HDL improved renal function, as we'll see in the DAPA CKD study, Um, cause as Monica recess and naturally says to some degree, this is a graphic again showing SLT two inhibitors effects both in the heart and kidney, as well as another organs, including the liver and the pancreas, blood vessels and adipose tissue. Most of these are, you know, theories about how s C L t two inhibitors provide benefit. Um, the data is limited, but we think that they cause improvement and they lead to improvement in human dynamics. Um, improvement in, uh, preventing adverse remodeling in the heart and the kidney, Um, as well as some anti inflammatory and antioxidant effects. So briefly, I just wanna mentioned, um, the DAPA CKD trial, which is also an important study. Um, this was 4300 patients with renal dysfunction, so they included patients with the G F R of 25 to 75 and urinary albumin albumin to creatinine ratios of 200 to 2500. Patients again were randomized to Dapple goofus and versus placebo. And in this population, the means CFR was 43. 67% of patients in both groups had diabetes and 11% of patients had heart failure. The primary outcome was a composite of sustained decline in G fr of at least 50% progression to end stage kidney disease or death from Reno or CV, or cardiovascular causes. The median travel was 2.4 years, and the trial was actually stopped early due to advocacy by the Data Safety and Monitoring Board. So these are the outcomes again, we see a significant improvement in the primary outcome in patients who were treated with that magnificent, with the number needed to treat of only 19. And there's also looking at the secondary outcomes, looking specifically at regional specific outcomes. There's a significant improvement in dappled with Jason and looking specifically at cardiovascular outcomes. There's also a significant improvement, with magnificent and then looking at death from any cause. Also, there is a significant improvement, so money just to interrupt for one second. So it sounds like so far, dapa is your go to s a l T two inhibitor. So far, the evidence weighs more towards data, right? So looking at heart failure patients, right? We just have studies on DAPA and pragmatism, and the data is a little bit better for DAPA, so I'll show you, you know, towards the end, I'll show you are proposed the pilot pathway that we're using for patients to start flt two inhibitors at Penn. And our first line is that with this in Okay, um, if it's not covered by insurance, then we'll try, uh, something or the other. And do you know if, um this this advanced renal insufficiency renal? Um effect is in patients with preexisting CKD or even if they don't have pre existing CKD. Um, you're saying the benefit in the Reno Outcomes. So So definitely in people who have preexisting CKD based on dapa CKD, which enrolled patients with the gear for of 25 to 75 there was an improvement in those patients. Um, and I think, um, I would have to look back to see if there was a subgroup analysis, but the data HF trial. Oh, no, not that patient. The Emperor Gryphus and Trial also showed a reduction in decline in G fr um, and that that population had a mean Jaafar of 60. So some renal disease. But I think overall there was a benefit there, too. Um, I would have to look at the specific subgroup analysis if there was one to see if they also looked at patients with normal radio function. So this one was 25 to 45. But some of the other studies said less than 30 they were excluded, right? So it sounds like 25 might be are cut off. Yeah, so I'll talk about that later. Also, like what cut off should we be using, But I think you're right. You know, based on this, it's probably safe to use it as long as the G F rise above 25 would be my thought. Monica, as long as you have the slide up, um, was there a greater benefit in the patients with worse renal failure versus mild renal failure? Um, that's a good question. I'm not sure if they looked at that specifically this subgroup analysis, but I think it's kind of just looking at the graphs. I couldn't tell if it was beneficial for people with more progressive renal failure and those with mild right here. This is the whole population. So the average here far was in the forties, and this includes everyone with 25 to 75. I'm not sure I would have to look back if they did a subgroup analysis based on the categories of renal dysfunction. Great. Thank you, Monique. Um, and again in this study, patients, regardless of whether or not they had diabetes, all the patients had the same treatment as well. Um, so I'll switch gears a little bit and talk about challenges and common questions that have come up as we've begun to incorporate SD lt two inhibitors in our practice here. Um, so this was an interesting poll that I found on a cc dot org. Um, as you all know, you know, when the STL t two inhibitor data first came out, there was a lot of debate on whether cardiologist should be prescribing these drugs. Or should it be endocrinology or primary care? Um, this poll was actually done just a couple of months ago, So things have changed since they first came out. Um, but basically, they asked, should cardiologist take lead in prescribing SCLC two inhibitors in patients with heart failure and most patients, not patients? Most cardiologists, um 67% agreed that if a patient meets indications for SCLC two inhibitors for heart failure, regardless of whether they have diabetes, we should be taking the lead in prescribing these drugs. Um, interestingly, 15% thought we should only do it if patients don't have diabetes. Um, And then there were some patients who thought it should be up to primary care random friends. Um, and the second question they asked is what? Our potential barriers or concerns, which is important, and this comes up a lot, Um, and the most common things that people said or difficulty with the approval process cost to the patient. Personal lack of experience with SCLC two inhibitors, um, as well as concerned for hypoglycemia and needing to adjust baseline diabetic medications. And these are really, um, synonymous with the concerns that we heard from cardiologists here. So I have a list of common questions that have come up and I'll try to address these. Um, so the first question people always wonder is, Do I need to worry about hyperglycemia with these patients? So this is a summary of, um, the adverse events in the two trials that we talked about data HF an emperor reduced, which looked at temple efficient. And you can see, overall, the rates of adverse events is pretty low throughout. Specifically, hypoglycemic events is a pretty low rate in both, um, trials. And there's no difference in the two arms. So I think it's not really something that we have to worry about. Um, I always look for it just when I follow up with the patients, but I don't think, um, it's something that we have to worry about when we prescribe these medications and then also, you can see the other things that we worry about our hypertension. And this was more prominent in the and magnificent trial versus adaptive Lifson trial, but not really much significant difference and difference in the two arms. Um, we think about volume depletion since these drugs do you have a diuretic effect? Um, we know adverse events, but again, not significantly different between the two arms. And then we also talked often about urinary tract infections, which some trials showed an increase rate of, um especially quickly and magnificent here. But again, it was seen in both arms. Um, genital infections, which I mentioned was seeing more in the employ. Beneficent arm and emperor reduced, um, and then perform material disease, which was actually seeing more, which was an increased risk in the Clinton Griffiths in trial in Kansas. Um, which is not looking specifically at heart failure patients. But there was an increased risk there. So that's another, uh, something else that we think about. The next question is for diabetics. Um, does the insulin regimen have to be adjusted? Do you have to adjust other diabetes, diabetic drugs? So we have recently started implementing these drugs in a standardized passion. So, um, personally, and I think most of us, um, we don't adjust diabetic drugs and insulin. I don't think we want to be that person. Um, so my patients who are on insulin or if they're on multiple diabetic medications, I'll usually just talk to the endocrinologist or primary care and have them come up with a plan on how to adjust those medications. Um, from what I've heard from entrepreneur ologists, um, if patients don't have, um, if they have room for improvement in their glycemic control, um, oftentimes you don't need to adjust it, um, insulin or other diabetic medications. But in patients who do have very tight control, um, they may decrease the insulin regimen by 25%. Um, and then so what side effects you need to look for. So a lot of these are things that we talked about. Um, you know, given that these medications do have some direct effect, they do cause some decrease in blood pressure. Things that I look for when I follow up with these patients is any signs of hypertension hyperglycemia? Um, any effect on the kidneys um, in terms of a k i hyperglycemia again, though, that's a pretty low risk. Um, and then I always ask for symptoms of U. T. I s or general infection, even though again, it's low risk. Um, when you repeat labs so again, there's no consensus guidelines on this, But I usually treated similarly to the way you would manage a patient that you start and trusted on, Um, since both of them have a diuretic effect, So usually I'll get labs in a week or two after starting the medication and then again a couple weeks after that, um and then another question that comes up is Do you need to decrease the patient's diabetic does when you start the STL t to inhibit our so we don't have any large scale data, Um, on whether you should or shouldn't do this. Um, there are some small studies, but they have the results of those were were burying. Some trials show that you should some trials showed that you didn't really need to. Um and I think the reason for that is patients really do vary, um, in terms of their dose of their diuretics and how responsive they are diuretics and how much of a direct effect they have with STL t two inhibitors. So I think again, this is similar to and presto um, you know, I think everyone, I'm sure here everyone's style differs a little bit in terms of whether or not you decrease your diuretic when you start in trust. Oh, I don't necessarily always decrease it. Um, I think in a patient where you're concerned about hypoglycemia or someone who is very well controlled in terms of their fluid status, you may want to decrease it, whereas others you may not. But again, I follow up closely with the patient after starting us guilty two inhibitor. So, um, you know, to troubleshoot if you need to decrease the directors or not. Another thought is that patients who have significant hyperglycemia may have more of an osmotic, their recess. So in those patients who may want to consider decreasing it, um, if we do decrease the diuretic, I wouldn't recommend decreasing it by more than 25%. So the next question this is something that Joyce you were asking about earlier. What g f r is acceptable. So I think this is also evolving. Um, dapa HF enrolled patients with the G F are above 30 and emperor reduced in patients with VFR above 20. Um, I think the package insert for Ambien with this instills test to discontinue the GFS less than 45. But I think that's going to change, especially with dapa CKD, which showed that you do have improvement in real outcomes with the G f r above 25. So I think I would be comfortable if the patient CFR is above 25. So next question is, are these medications FDA approved for patients who have heart failure without diabetes and does the insurance cover them? So, as you may know, DAP magnificent was FDA approved in May of last year for patients with our flair without diabetes. Um, and I have had patients. Um, I have had patients whose insurance does cover them. Um, and Bob Livingston has not obtained this approval yet, but they are seeking the same approval. Um, and you know, we'll partner with our pharmacists to really, um, tried a publicist. And first, if that insurance doesn't cover that for some reason to try and look at this book is And after that, um, and the copays? Um, probably very based on the insurance. Um, but I think the coverage probably will get better, especially as the hard floor guidelines include SD lt two inhibitors, which they haven't yet. Since we don't have updated guidelines, Another common question is R S d l C two inhibitors beneficial in half path. So we don't know the answer to that yet. Um, this is being studied, um, in the, um into trials. The Emperor, um, Emperor Preserve trial is looking at M magnificent and deliver is looking at data with prison patients who have half path and have diabetes. I'll try to start S C L T two inhibitors in those patients, given the potential benefit. And if they have diabetes, they need indication for that reason. But hopefully we'll have more data when we have the results of those two studies. This is another common question. Um, when should you start? S d l t two inhibitors relative to other heart failure therapies for half breath. Um, so I don't think anyone knows the answer to this. I don't think we'll ever know the answer to this. And patients who are started on s DLT inhibitors in the trial were already on a background of standard heart failure therapies. Um, personally, I usually go in the order. That patient, the clinical trials came out. So I'll start an Ace Arbor Arnie and being a blocker. Um, that said, you know, if I can start one of those for any reason or if I can't up titrate them, but there's room to start s dlt two inhibitor. I'll do it then. I don't necessarily wait to do it in a certain order. Um, but I don't think we'll we'll really I ever have data to support doing it one way or the other. And then, lastly, is it safe to start as dlt two inhibitors in D compensated heart failure? So we don't know the answer to that question. We don't have a large scale trials looking at this. Um, but I just wanted to show you this study, um, which was emperor response HF for acute heart failure. And this was a randomized, placebo controlled small pilot study. So, um, there was only 80 patients enrolled in the study who had acute decompensating heart failure, and they were randomized to ample beneficent versus placebo. So half of these patients had the noble heart failure. Um, and the primary outcome that they looked at, um showed no difference. So no difference in the dystonia score. No difference in diabetic response length of stay of the hospitalization or change in anti pro BMP between the two groups. Um, but I think most importantly, as you can see on the table, um, there was no difference in adverse events between the two groups. So only 40 patients who received and magnificent But in this in this study, um, it was safe and well tolerated. Um, and there were no significant adverse effects. I think that's important. Um, and then the study also looked at an exploratory analysis. So this is really more hypothesis generating because it wasn't power to look at this. Um, but they found that MPEG Lifson did reduce a combined endpoint of in hospital worsening heart failure, re hospitalization for heart failure or death at 60 days. So I think, um, that's, um, intriguing and and may have some, um, and it may have some benefit in those outcomes, but we would need larger studies to really know that. So lastly, I'll just go over to pathways. Um, so this is probably hard to see. Um, but I just wanted to show you, um this this is a pathway that we designed here at Penn, um, to as a pilot study to start S d l t two inhibitors in patients who are discharged from our heart failure service. Um, with the goal of increasing utilization of SGL T two inhibitors in this population, I'm going to say out loud that Monique has done a great job to socialize this.