Recent Clinical Trial Evidence in the Management of Patients With Heart Failure
In this podcast series, moderator Seth S. Martin, MD, MHS, examines key practice-changing clinical trials and explores the future of cardiovascular medicine, including the development of cutting-edge technologies, innovative approaches to implementing prevention guidelines, and more.
In this episode, Dr Martin interviews Alex Tarlochan Singh Sandhu, MD, MS, about the management of patients with heart failure (HF), including gaps in patient care, recent clinical trial evidence in the STRONG-HF, IMPLEMENT-HF, PROMPT-HF, and EPIC-HF trials, and digital health opportunities.
Additional Resources:
Mebazaa A, Davison B, Chioncel O, et al. Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): a multinational, open-label, randomised, trial. Lancet. 2022;400(10367):1938-1952. doi:10.1016/S0140-6736(22)02076-1
Ghazi L, Yamamoto Y, Riello RJ, et al. Electronic alerts to improve heart failure therapy in outpatient practice: a cluster randomized trial. J Am Coll Cardiol. 2022;79(22):2203-2213. doi:10.1016/j.jacc.2022.03.338
Allen LA, Venechuk G, McIlvennan CK, et al. An electronically delivered patient-activation tool for intensification of medications for chronic heart failure with reduced ejection fraction: The EPIC-HF Trial. Circulation. 2021;143(5):427-437. doi:10.1161/CIRCULATIONAHA.120.051863
Sousa C, Leite S, Lagido R, Ferreira L, Silva-Cardoso J, Maciel MJ. Telemonitoring in heart failure: a state-of-the-art review. Rev Port Cardiol. 2014;33(4):229-39. doi:10.1016/j.repc.2013.10.013
Masterson Creber R, Dodson JA, Bidwell J, et al; American Heart Association Cardiovascular Disease in Older Populations Committee of the Council on Clinical Cardiology and the Council on Cardiovascular and Stroke Nursing; Council on Quality of Care and Outcomes Research; and Council on Peripheral Vascular Disease. Telehealth and health equity in older adults with heart failure: a scientific statement from the American Heart Association. Circ Cardiovasc Qual Outcomes. 2023:e000123. doi:10.1161/HCQ.0000000000000123
TRANSCRIPTION:
Hello, and welcome to CardioCare Now, a special podcast series led by Dr Seth Martin. Dr Martin is a cardiologist and an associate professor at Johns Hopkins University School of Medicine in Baltimore, Maryland. The views of the speakers are their own and do not reflect the views of their respective institutions or Consultant360.
Seth Martin, MD, MHS: Welcome everyone back to the CardioCare Now podcast. We are really pleased to have Dr Alex Sandhu from Stanford join us as our guest today. Dr Sandhu is an assistant professor at Sanford. He's a heart failure specialist and has really been a tremendous collaborator in our American Heart Association, our AHA HealthTech FRN Network, where he has been leading our collaborative team on a project using health technology to engage patients and improve guideline-directed medical therapy in the heart failure population. This is just one of multiple projects that Dr Sandhu has worked on in in his area, and he's really a leader in the cutting edge of heart failure care. I'm really, pleased to have him join us and just have the chance to pick his brain and learn from him, alongside the audience. So, Alex, Dr Sandhu, great to have you joining the podcast.
Alex Sandhu, MD, MS: Seth, thank you so much for having me on. It's a real pleasure.
Dr Martin: Yeah. It's great to just have this time to talk about a topic that we're both, very interested and passionate about, and that's the care of heart failure patients. I wanted to get your thoughts just, first of all, around sort of what the current problem is, you know, based on your perspective observing the barriers to heart failure care on the front lines as a heart failure specialist, but also, you're uniquely familiar with the literature on heart failure care and the gaps, in care that's been observed with GDMT. We now have 4 pillars of heart failure management for patients with HFrEF, but there have been significant gaps, and I wonder if you could just share a bit more details of what those gaps are that you're seeing in heart failure care and your latest framing of the problem.
Dr Sandhu: Yeah. Thank you, Seth. I think the background here is really important. Heart failure, as we know, causes substantial morbidity in terms of mortality, hospitalizations, and impairment of quality of life. We're incredibly lucky that we have multiple evidence-based medications that reduce the risk of death and hospitalization and improve how patients feel with relatively modest side effects proles. Current estimates, the kind of combination of therapies that are commonly referred to as guideline-directed medical therapy or GDMT reduces the risk of death by over 70% in patients with heart failure with reduced ejection fraction. But, unfortunately, data from multiple health systems now continue to reflect suboptimal treatment among patients with heart failure. This is consistent across inpatient and outpatient registries, in the fee-for-service US health system, in the VA, and outside of the US as well. While we've had improvement in inpatient quality of care led largely by inpatient registries such as the American Heart Association's Get With the Guidelines, we continue to see substantial inertia In optimizing patients' medications after discharge. In most national registries, less than 40% of eligible patients are on mineralocorticoid receptor antagonists or MRAs. We continue to see sacubitril/valsartan rates uptrend, but quite slowly with the vast majority of eligible patients not on sacubitril/valsartan.
And then most patients who are discharged on medical therapy, have very little up-titration, and we saw that from the CHAMP HF registry where the vast majority of patients stay on less than fifty percent of the target doses for both beta blockers and RAS inhibitors. I think we have very large gaps in the current use of medical therapy compared with where we want to be to really try to optimize our outcomes.
Dr Martin: Yeah. Thank you so much for that framing and background, it is the case in much of cardiology and medicine that there are gaps in the use of evidence-based medical therapies, but it is particularly striking in heart failure, given the sheer number of people who have heart failure, the morbidity and mortality associated with it, as well as the large, you said 70% reduction in mortality associated with the use of GDMT. So, it really is particularly striking in the heart failure population. And there are multiple barriers. I get you know, I guess before we move on to some of the recent clinical trial evidence, I'm just curious, what are some of the key barriers you see in the literature and your practice in terms of getting patients started on the four pillars of GDMT and up-titrating doses.
Dr Sandhu: Yeah, it is a really important point to think through what those barriers are before we understand kind of how we can move forward. I like to start by talking about cost because it's often one of the most cited barriers. And out of pocket cost is an important barrier, especially for the newer therapies, the sacubitril/valsartan and SGLT inhibitors, but that's not the main driver. And I say that because even in the VA where medication costs are minimal and out-of-pocket medication costs are minimal, we see very similar rates of treatment with these brand-name therapies as we see outside of the VA. Even for a therapy such as MRA, which has been generic for years, we continue to see very low rates of treatment with MRAs. So, I think we must think about the barriers beyond cost, and I like to bucket them into clinician-level barriers, health-system-level barriers, and patient-level barriers. To start with thinking about some of those clinician-level barriers, I think there are gaps in our understanding of the benefits and risks of these medications.
And there's somewhat of a myth of kind of the stable heart failure patient. Someone's admitted to the hospital, is very symptomatic. They're decongested with loop diuretics. And after discharge, they might be minimally symptomatic. And there's some assumption that a patient that's minimally symptomatic is relatively stable and low risk.
Well, that's not the truth that heart failure has a waxing and waning course, but it is a progressive condition. And without optimal therapy, those patients remain at substantial risk. I think the other major clinician-level barrier is that all of our patients, and especially our heart failure patients, have many comorbid conditions. And there's only so much time in a given clinical encounter to focus on heart failure, as opposed to the many other concerns and conditions that we have to help our patients with. And I think that kind of ties into the next set of barriers with regard to health-system-level barriers.
Traditionally, medication titration happens during clinic encounters, But there's only so much bandwidth with regard to clinic volumes. We already see that wait times for specialty care continue to increase, and it's likely an even larger problem for primary care. And I think the second kind of health-system-related challenge is that health-system reimbursement is on a fee-for-service basis. Our system doesn't incentivize us to focus on optimizing medical therapy. And in fact, there are in some ways financial disincentives.
It takes longer to check on your patients after they leave a clinic visit to see how they feel about new medications. It takes longer and requires additional clinic investment to be calling patients to remind them about the lab checks that you have to do to make sure that patients, you know, are safely up-titrated on medical therapy. And finally, I think, you know, access to care in general and especially access to specialty care is a major barrier, especially for patients in rural communities and in safety-net communities.
The vast majority of heart failure care is not delivered by heart failure specialists like me. It's delivered by general cardiologists or, for many patients with heart failure, most of their care, if not all, is delivered by their primary care clinician. There are definitely, workforce supply considerations.
And then finally, I think, a lot of it comes down to patients. Have we done enough to help patients understand the reasons for medication therapy optimization to know where the goalposts are, where they currently sit, and how they can get to better therapy? Often, as mentioned before, patients feel better after they leave the hospital. They already feel better, they got put on multiple medications, and they're not quite sure what the benefits are of adding additional therapies. And there are real concerns about polypharmacy and side effects, especially for our older patients with heart failure who take so many medications for other reasons.
And then similarly to the challenge of titration in the clinic, there's a real burden with regards to both the cost and time of going to the clinic frequently for medication adjustments, and there's a parallel concern about the safety of up-titrating medications in-between visits. So, I think there are many barriers on the clinician, health system, and patient level that all contribute to this kind of major gap that we have.
Dr Martin: Thanks, Alex. That was a really insightful and clear description of the key barriers. I mean, this is a large problem with large Barriers. So, it's going to take a large and highly innovative solution to really start to get to where we need to be, but we have started to see some glimpses into this with some of the recent clinical trials. And tying in with some of what you just described there related to heart failure hospitalizations, we had an interesting result with the IMPLEMENT HF trial using a pharmacist-physician GDMT team there for heart failure patients while they were hospitalized, and then we had the STRONG HF trial, looking at rapid up-titration of GDMT post-discharge.
So, I know you're intimately familiar with these trials, and these are helping inform some of the strategies that can be taken. And ultimately, we may need a hybrid of strategies that work to really get to where we want to be. But I wonder, do you want to dive into those trials a little bit more what you were impressed by with those trials, and what some of your key takeaways were?
Dr Sandhu: Yeah. I'd absolutely love to. Two exciting trials that, as you said, I think inform us about the direction we need to go and some novel potential strategies. IMPLEMENT HF is an exciting trial led by Ankit Bhatt when he was at the Partners Health Care System, which took patients who were hospitalized with heart failure with reduced ejection fraction. And I think what was interesting, these are not patients who are all hospitalized for heart failure. They could have been hospitalized for any reason, but they have heart failure and are in the hospital. The trial recognizes the fact that being in the hospital is an incredibly unique opportunity to optimize care, regardless of the reason a patient is there. Patients get frequent laboratory tests, frequent assessments for symptoms, and frequent vitals monitoring.
So, they randomized these individuals to either virtual care team consultation or usual care. The virtual care team provided daily recommendations on GDMT or up-titration. As you mentioned the virtual care team consisted of both a clinician and a clinical pharmacist. And what they found was across 250 hospitalizations, those that receive virtual care had larger increases than medical therapy. They were far more likely to be started on beta blockers, MRA, and SGLT2 inhibitors. So, I think it's an example of kind of thinking outside the box and using routine clinical encounters and leveraging the full spectrum of the care team to really move the needle. And I think it also demonstrates that while we're talking a lot about optimizing outpatient heart failure care, that a lot of that starts with our highest-risk individuals when they're in the hospital and doing as much as we can to optimize their care there.
I think the counterpoint to that is even with such a great, powerful intervention, there were still substantial gaps in optimal medical therapy at the time of discharge. And I think this points to the fact that we're still going to need to find solutions for improving medical therapy post-discharge.
Dr Martin: Absolutely. And so, the post-discharge period leads to the STRONG HF results, as well as just some of the team-based approaches that are happening at health systems for early, you know, clinic follow-up with nurse practitioners and heart failure teams, do you want to, speak to some of that? And then, of course, we are going to transition to talking about the direct work that that you're leading and how some of this comes together in the .HF trial, but, let's think through this post-discharge period a little bit more first.
Dr Sandhu: Yeah. I would love to. So first, I think, any of this conversation has to include STRONG HF. So, multiple trials have demonstrated the benefits of heart failure medical therapy are observed early in the course of treatment. But the safety and net benefit of rapid optimization of therapies was unclear, I think, until STRONG HF.
So STRONG HF, took 80 hospitals across 14 countries and enrolled over 1000 patients with heart failure. They randomized them to either usual care or rapid medication up-titration combined with close monitoring for signs of decompensation. And what they did was they up-titrated therapy a couple of days before discharge, and then they, again, up-titrated therapy to kind of maximally tolerated or optimal doses 2 weeks after discharge. So, I think far more of an aggressive up-titration protocol than what's been traditionally used in clinical care. And the results were quite dramatic.
They had much higher rates of optimal doses or target doses for renin, angiotensin system inhibitors, Beta-blockers, and mineralocorticoid receptor antagonists. What they found is those in the rapid up-titration arm had significantly lower rates of all-cause death and heart failure hospitalization at 6 months. I think STRONG HF, in many ways, has created the emphasis on us needing to find ways to rapidly and safely up-titrate therapies as part of routine care. It really set the agenda, and now we have to try to develop strategies for doing that. I think there are two other studies that are really worth mentioning that I think have also been quite innovative and really helped us think through what some of those strategies should be.
The first is, the PROMPT HF trial, which was done out of Yale's health care system led by Tariq Ahmad, MD, MPH, and it took 1300 patients outpatients with heart failure reduced ejection fraction, and it randomized their clinicians to either the usual care or EHR clinical decision support alert notifying that clinician at the time of an encounter that the patient has an opportunity for GDMT up-titration. And it was a positive trial, that showed that 26% of the intervention arm had increased in their GDMT compared with 19% of the control arm. So, I think it’s powerful that an intervention that would be easy for a health system to implement can make a large difference. But I think it's also quite striking that the vast majority of patients still didn't have an up-titration in their medical therapy. I think it shows that we need to go beyond just thinking about how we nudge for medication up-titration during a clinical encounter and have to think about ways to facilitate that up-titration both during and between visits and not just provide the information that is needed.
And that's what kind of leads to EPIC HF, which in my opinion is one of the most important studies for optimizing medical therapy in cardiovascular disease in the last several years. And this trial was led by Larry Allen at Colorado. They took 290 outpatients with heart failure with reduced ejection fraction, and they randomized them to either usual care or what I would describe as a fairly simple intervention. They gave them a 3-minute video discussing the benefits of medical therapy and a 1-page checklist of heart failure medications. The checklist included what the patient's medications were and what the target doses of those medications were.
In both the video and the checklist, it gave patients the basic message of working with their clinician to make one positive change. They sent those notifications to the patients 1 week, 3 days, and 1 day before the clinic visit. And with that relatively simple intervention, nearly 50% of the intervention arm had therapy intensification compared with 30% of the usual care arm. I think it's an incredibly remarkable study and one of the first studies to show us the incredible power of empowering patients and using the patient's voice to improve the quality of care.
Dr Martin: I completely agree. It's a very powerful study in that regard and something I totally buy into. In fact, we've taken some inspiration from the software approach that Larry Allen and the team used to create animated videos and create patient education within our individual projects in the network, as well as collaborative projects. So, we're grateful to him for guiding us to that powerful approach to patient education.
So, we'll get a little bit more into our collaborative project, but at a high level, these are really four complementary trials that have immediate takeaways for clinicians on the front lines today, whether it's around the power of incorporating more patient education materials into your practice, particularly pre-visit, whether it's incorporating EHR prompts and nudges, whether it's implementing more of a team-based approach for patients with heart failure, whether or not they're hospitalized with heart failure, taking advantage of having someone who's in the hospital for any reason to optimize their heart failure drugs and then focusing on rapid up-titration post-discharge, again, ideally, using a team-based approach to facilitate frequent touch points and up-titration, as well as, you know, lab measurement to and so forth to assess safety.
So, these are four powerful and complimentary trials that really did a nice job informing the strategies that we wanted to take in the collaborative network. So, do you want to share a bit about what we're doing with .HF and how we're trying to bring some of these learnings together and innovate with the ENGAGE HF app and the future trial we're doing to try to move this in a positive direction for heart failure patients.
Dr Sandhu: Yeah. Denitely, Seth. And I agree completely. I think we learned a lot from these four studies and others in this space and other thought leaders in this space about how we really have to leverage the power of patient engagement and buy-in, along with facilitating clinician up-titration making it easier for them by collecting data to help make it easier during and between traditional clinical encounters, and that we think that digital health can play a huge role in doing that. So, .HF, as Seth has mentioned, is a multicenter collaboration across five American Heart Association health technology and innovation strategically focused research network centers: Johns Hopkins, University of Michigan, Cincinnati Children's, and University of Washington as a single center, Boston University, and Stanford.
What we're doing is working together to develop and test a digital toolkit to improve post-discharge heart failure care with the goals of integrating patient education engagement, along with clinician-level nudges to optimize therapy. And we've approached this project in multiple phases. Our first phase started with human-centered design work led by your team, Seth, at Hopkins where we gathered patients with heart failure, caregivers of patients with heart failure, and clinicians. We got their feedback on what their thoughts are about barriers to post-discharge heart failure care and especially heart failure medication optimization. We then took those learnings as well as the learnings of other studies in this space and developed a smartphone application, ENGAGE-HF app, that combines patient education with animated educational videos.
As you mentioned, we use the same software that Dr Allen's group used in EPIC-HF. We also incorporated monitoring of ambulatory vitals and health status and embedded a medication checklist very similar to EPIC HF within the app. Then we created a parallel clinician dashboard that collects all that information to both nudge medication up-titration during and between visits and to make it easier for clinicians to access and review home vital signs and home health status. So, we're now testing that platform in a pilot study before planning to adapt that and then test it in a multicenter clinical trial to evaluate if it improves heart failure medication optimization. And I think what's really exciting about this is that in parallel with us doing this in the United States, the team at the University of Washington and Cincinnati Children's led by Chris Longenecker have developed a collaboration with Luisa Brandt at Universidade Federal de Minas Gerais in Brazil.
What they did is they took the application that we built in the US, as well as lessons, that their own very established telehealth center has done doing remote heart failure management, and they built a Brazilian version of the app, and they're currently testing that in a multicenter trial in Belo Horizonte, Brazil. I think, overall, our hope is that we can provide a guide for how we can use digital health tools to empower heart failure patients and make it easier for clinicians to have the data and the patient engagement to optimize therapy outside the hospital.
Dr Martin: Yeah. Thanks, Alex. Thanks for your leadership on this. And we, we don't yet have results to share with the audience, but certainly down the line. This is an exciting project, and we're excited to share the results of this effort. And I love the fact that there's a global collaboration with our colleagues in Brazil and the opportunity for reciprocal innovation.
As we get towards the end of our conversation, I wanted to just think futuristically. Let's say, our pilot and our trial go really well, and there are others that are focused on this big problem as well, doing important studies and trials. As things continue to advance and we think about the expansion of digital health and artificial intelligence and the changing and shifting landscape towards value-based care… by the way, we didn't have time to get too much into that today, the value-based care, but you also were a co-chair on a statement on value-based care.
So, just thinking about how these innovations, both in terms of care delivery technology, as well as the way that care is incentivized and reimbursed. Where do you see this going? If you think of 5 years, 10 years from now as your kids are or getting older and go into higher grade schools and so forth. You know, what do you think this is going to look like for the heart failure patient? What if we're a clinician in the hospital or the clinic, what is it going to going to look like compared to today?
Dr Sandhu: Yeah. Thanks for that wonderful question, Seth. I think it comes down to the fact that patients spend almost all their time outside of the hospital and outside of the clinic. And I think the future of heart failure care is going to be continuous care, based on how someone's doing in their daily life and not with just, you know, every 3-month clinic visits. Heart failure is such a waxing and waning condition, with ups and downs that are unpredictable. The idea of kind of scheduling a visit and seeing how someone's doing in 3 months, 4 months, or 1 month is going to end up being suboptimal to just having regular continuous care that's optimizing their medications, monitoring for signs of decompensation on a daily basis. It's going to allow us to rapidly adjust medicines, deliver timely education, and ward off decompensation before they end up in the hospital.
I think there are big steps that we need to take before we get there. I think developing the right digital health tools and evaluating those digital health tools is critical, and I'm so excited about our collaboration and what we and many others are doing in terms of developing and then evaluating the right tools to help us provide that care. And I think you brought up the other, you know, huge barrier, which is going to be health system design and reimbursement. And I think in the future, we are heading for a world where, especially for chronic conditions that require continuous care to give our patients the best care, we're going to have to shift to systems that reimburse health systems for the quality of care and the global care they provide rather than an individual clinic visit or an individual hospitalization.
Dr Martin: Yeah. Thanks, Alex. I really like the way you described that as the shift towards a continuous care model, and that can apply to heart failure and other cardiovascular and chronic conditions and really could be an approach that could much better serve our patients.
I did want to leave the audience just with any of your kind of recommendations for further reading or resources. Of course, we did mention four key trials: IMPLEMENT HF, STRONG HF, PROMPT HF, and EPIC HF. If you're interested, would encourage folks to check out those manuscript publications. But are there other resources, Alex, that you wanted to recommend to the audience?
Dr Sandhu: I think each of those trials, as you mentioned, is an important one. There was also a phenomenal statement paper about telehealth and health equity in older adults with heart failure that was released by the American Heart Association. And I think it not only covers a lot of the same topics that we're describing now but also really frames it through the lens of health equity. And I think whenever we have conversations about digital health. I know you and your group at Hopkins are incredibly passionate about this, Seth.
We have to think about how we design health technology for all of our patients, and we use it to narrow, rather than widen disparities. So, I think that's an incredibly, important paper to kind of include in this conversation.
Dr Martin: Thanks so much, Alex. I really appreciate you taking the time today. You're really uniquely qualified to talk on this topic. So, it's really fun to get to pick your brain, and I hope the audience found this information useful, and thanks so much for tuning in.
Dr Sandhu: Yeah. Thanks so much, Seth.
For more cardiology content, visit our website, consultant360.com.