This has been a great program. I’ve learned a lot. We covered lots of ground about antithrombotic therapy, coronary artery disease [CAD], and peripheral artery disease [PAD] in general. Let me turn to our distinguished panel for some closing thoughts. I’ll start with you, Manesh. Any final points [that] you want to make for the audience?

Deepak, it’s been fun and exciting. It’s fun to talk to people about evidence for the things we see. We’ve learned over the last decade is that vascular disease unfortunately is still the leading cause of cardiovascular mobility issues and mortality. As we have more options, which is a good thing, we have to get the right dose for the right patient at the right time. Some of that is understanding the risk and the risk benefits that we’ve talked about. Concerning patients with polyvascular disease, patients with broad thrombotic risk, it’s important to understand how you can make them have better outcomes. We’ve talked about that today. Hopefully it’s something that people will take home.

 I agree. It’s been a wonderful panel. I’m thrilled to be part of this. My take-home message would be to focus on identifying these polyvascular patients. Because they’re such high-risk patients, it’s important not to be focused on the coronary artery disease. But if patients have coronary artery disease and vascular disease in another territory, then that’s the pinnacle of our risk. Diabetes on top of that is going to be at that highest cardiovascular risk, so we need to talk with our patients about the fact that they’re at a higher risk and how that guides our recommendations for changing medications. Oftentimes patients can be resistant, understandably, to wanting to add another medication. But part of patient-centered decision-making is educating them that this is why that goes a long way.

We need to educate the medical community about those risks that identify polyvascular disease, diabetes is a real risk amplifier. Great points. Eric, any closing thoughts?

 This was a fantastic discussion. For everyone watching this, it’s important for us to not be fearful of making a change in our practice. We’ve been set in our ways for a long time, but we’ve had these accumulating data. It’s time for us to be open-minded about making changes that benefit our patients. We’ve heard today that there are many agents that can optimize long-term cardiovascular and limb-related risk outcomes and improve the care for our patients, so it was a great discussion.

Absolutely agree and Sahil, any final thoughts?

 That’s really important. What Eric just said is that we’ve been in this mode of using dual-antiplatelet therapy for extended amounts of time with very little evidence, particularly in the PAD population, which is the predominant part of my practice. It’s great that we have strong evidence to support the use of dual-pathway inhibition. We need to get the message out to our referring doctors and our patients that this is the way forward to optimize the risk.

Terrific. Marc, you’ll get the final word.

 It’s been an honor to be part of this panel. We’ve learned that we have a gap in terms of the evidence and how we treat our patients. Part of that is that we have a lot of patients to see. We’re all very busy clinicians. Everyone wants to do their best. But understanding who the highest-risk patient is and what the best evidence is needs to be at the top of your mind as you see your clinic patients, and polyvascular disease resonates. I learned that term from you, Deepak, many years ago. It has been shown in every study to be such a potent marker of risk and beneficial for some of these strategies and other things like diabetes. We need to take that into the clinic and start treating our patients better.

I couldn’t agree more. Hopefully the audience found this exchange of ideas informative, interesting, and educational. Hopefully these are things you can take this into your practices. As I mentioned, I learned a lot. A final point I’ll make is that when you’re thinking about coronary artery disease, think about the whole patient. For that patient you’re seeing for 1 specific condition, that might be the issue in the office for that day. But they may have other risk factors. They may have plaque in other arterial territories. We talked a lot in this session about polyvascular disease, but keep in mind that CAD, PAD, and cerebrovascular disease can coexist. Even though the patient might be seeing you for angina in that office visit or hospital encounter, think about all those associated risks. If you identify those associated risks, you realize that it’s a very high-risk patient, the sort of patient for whom we want to do everything possible to reduce their risk, including intense lifestyle modification. Beyond that, in many cases pharmacotherapy, polypharmacy with wisdom and caution, and in some cases procedural care are all complementary approaches, not competitive approaches.

Thanks to all of you on our panel and to our audience for this rich and informative discussion. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming 

 and other great content right in your in-box.

A panel of expert cardiologists share their concluding thoughts on management of polyvascular disease in clinical practice.  

Concluding Thoughts

Eric Secemsky, MD

Joshua Lynch, DO, EMT-P, FAAEM, FACEP, University at Buffalo Jacobs School of Medicine & Biomedical Sciences

Juan Pablo Arab, MD, is a transplant hepatologist and an associate professor of Medicine at the Division of Gastroenterology at Western University.

Reflecting on Resmetirom’s Historic FDA Approval for MASH

On March 14, 2024, the US Food and Drug Administration (FDA) made history when it granted accelerated approval to Madrigal Pharmaceuticals’ resmetirom (Rezdiffra), making it the first and only treatment for noncirrhotic nonalcoholic steatohepatitis (NASH), now known as 

metabolic dysfunction-associated steatohepatitis (MASH)

One year later, resmetirom’s impact on clinical practice and patient care continues to evolve. In recognition of the anniversary of the landmark decision, the latest 

 spotlights a conversation between a trio of subject matter experts reflecting on the past year of having resmetirom as a treatment option for patients, remaining unmet needs in MASH management, and the evolving therapeutic pipeline poised to further transform care.

Estimated to affect more than 30% of the global population, MASLD is the most common chronic liver disease around the world. MASH represents an advanced stage of MASLD and has historically lacked treatment options beyond lifestyle changes with diet and exercise. In the absence of pharmacologic therapies, weight loss served as the cornerstone of disease management.

This changed in March 2024, when resmetirom became the first and only FDA-approved MASH therapeutic, earning accelerated approval for the treatment of noncirrhotic MASH with moderate to advanced fibrosis. Although lifestyle interventions continue to play a pivotal role in MASH care, as the thyroid hormone receptor-beta selective agonist is indicated in conjunction with diet and exercise, they are no longer the only tools available for disease management.

 on the 1-year anniversary of resmetirom’s FDA approval and the evolving landscape of MASH management, moderator Jeff McIntyre asks Mazen Noureddin, MD, MHSc, and Juan Pablo Arab, MD, about the clinical impact resmetirom has had since being approved and whether it lived up to the expectations set for it as the first-ever MASH therapeutic.

Noureddin begins by highlighting resmetirom’s “game-changing” impact, citing strong clinical results, guideline updates, and the shift toward noninvasive testing. He notes that patients are seeing benefits and that long-term data continues to support the drug’s efficacy.

Arab expresses agreement, emphasizing that resmetirom has not only improved patient outcomes but also changed how clinicians approach MASH. Previously, primary care providers and endocrinologists were reluctant to screen for at-risk MASH due to a lack of treatment options. Now, with an FDA-approved therapy, he says there is greater urgency in identifying and managing these patients.

Discussing challenges, Arab points to the need for broader screening, improved access to noninvasive tests, and overcoming reimbursement hurdles, additionally stressing that implementing a new treatment requires systemic change across healthcare.

Noureddin adds that while hepatology clinics were well-prepared for resmetirom’s arrival, uptake in gastroenterology practices has been mixed. He sees a need for more education on noninvasive tests and fibrosis staging but says that overall, awareness and access are improving. He remains optimistic about the drug’s future and the potential for combination therapies to further transform MASH treatment.



Jeff McIntyre is the vice president of Liver Health Programs at the Global Liver Institute.

Mazen Noureddin, MD, MHSc, is a professor of medicine and a transplant hepatologist at Houston Methodist and director of the Houston Research Institute.

Juan Pablo Arab, MD, is an associate professor of medicine in the division of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University School of Medicine.

Noureddin has relevant disclosures with Altimmune, Madrigal Pharmaceuticals, Merck, Takeda, Terns, and others. Arab and McIntyre have no relevant disclosures.

US Food and Drug Administration. FDA Approves First Treatment for Patients with Liver Scarring Due to Fatty Liver Disease. March 14, 2024. Accessed March 13, 2025. 

https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-liver-scarring-due-fatty-liver-disease

Brooks, A. Stephen Harrison, MD: Promising Phase 3 Data for Resmetirom in NASH, Fibrosis. HCPLive. February 7, 2024. Accessed March 13, 2025. 

https://www.hcplive.com/view/stephen-harrison-md-promising-phase-3-data-resmetirom-nash-fibrosis

In the opening segment of this 6-part HCPLive RX Review, experts reflect on resmetirom’s FDA approval for MASH and clinical challenges to implementing it.

Juan Pablo Arab, MD

Experts continue the discussion on treat-to-target in CD, highlighting monitoring treatment response.

Monitoring Treatment Response in Treat-to-Target in CD

This is a video synopsis/summary of a panel discussion involving Marla Dubinsky, MD; David Rubin, MD; Miguel Regueiro, MD; Remo Panaccione, MD, FRCPC; and Sara Horst, MD, MPH.

The experts delve into the reassessment and monitoring strategies for patients undergoing treatment for Crohn's disease. The discussion revolves around determining when and how healthcare providers should assess if the patient is progressing in the right direction and whether the current treatment is effective.

The speakers emphasize the importance of early targets, including clinical response, clinical remission, and biomarker trends. They stress that if patients don't meet these early targets within a reasonable timeframe, there is a need to reassess the monitoring strategy. The concept of treat-to-target is discussed, where clinical response should be assessed within 4 weeks of initiating therapy.

The role of biomarkers, such as fecal calprotectin and c-reactive protein (CRP), is highlighted, with a suggestion to monitor them as early as week 4 and subsequently at 8 weeks, 12 weeks, and every 3 months. The biomarker trends help identify whether the therapy is working or if there's a need for intensification or a change in treatment.

The speakers also touch upon the challenge of convincing patients who feel well to undergo monitoring, emphasizing the importance of using patients as their own control. The goal is to establish a baseline understanding and ensure that even when patients are in endoscopic remission, ongoing monitoring remains crucial.

Overall, the discussion emphasizes the dynamic nature of monitoring strategies, adapting to individual patient responses, and using a combination of clinical, biomarker, and endoscopic assessments to guide treatment decisions effectively.

Video synopsis is AI-generated and reviewed by HCPLive editorial staff.

Marla Dubinsky, MD

 One of the things I’m curious about is does it make a difference if a patient is biologic naïve and comes to you with moderate to severe psoriasis, vs a patient who has been on several biologic agents? Does that change how you approach which agent you’re going to put them on?

 It does, actually. For the patient’s biologic experience, I want to know what biologic they took and what their experience was. What adverse effects did that patient experience? Did they have a good experience? Did it work well for them? Was there some reason, such as loss of insurance, that they had to interrupt that? And if there wasn’t a reason not to restart that therapy. I will usually restart the patient on that therapy. If a patient had a loss of efficacy, they were unsatisfied, they had some adverse effect or lab abnormality, I will absolutely switch them to a different class. For the biologically naïve, approach them based on their comorbidities, their presentation, and what’s important to the patient. I approach them differently, but those are some of the nuances in terms of selecting an agent for them.

 One of the things about being a nurse practitioner [NP] and a physician assistant in dermatology is that we often manage the chronic diseases in dermatology, such as psoriasis and atopic dermatitis. Some of the roles that we play in the management of plaque psoriasis is that we can take the time to develop a relationship with these patients, spend some time educating them about their disease, reviewing all the treatment options that are available, and then really working with the patient to come up with a decision that’s going to be helpful for the patient and that the patient can live with and be successful with.

Nurse practitioners and PAs [physician assistants] can impact the quality of life of these patients with psoriasis and psoriatic arthritis. The most rewarding days I have are when I see those patients come in who were covered head to toe or who were just miserable in pain, who were socially isolating, but they happen to be on a good agent for their psoriasis and feel like they have a new lease on life. They’re engaging in their family activities. They’re holding down jobs and successful. They’re traveling and going on vacations. They’re going to the gym and working out, and subsequently, their diabetes is getting better under control. They’re losing weight. You can really see the transformation in these patients, and that’s something that’s really, as an NP, I really value. As a PA, Matt, you’ve seen these patients and transformed their lives, and it can be remarkable. When you counsel patients about psoriasis, what are some of the challenges you face in helping patients come to terms with their psoriasis and then helping them move past them and be successful in their treatments?

The first challenge that I would like to pinpoint is helping patients accept the chronicity of their disease. Many patients come in with the expectation that there’s something we can give them, something we can do for them that’s going to make this problem go away. It’s important to have that discussion, as we’ve mentioned, over the chronicity of the disease. You pinpointed that those patients sometimes have trouble with compliance with their therapies.

Sometimes that’s because we’ve taught them that with topical therapies, they should use them intermittently. We have to make sure we educate our patients when we put them on a systemic agent, whether it’s an oral agent or an injectable agent, to understand that these are not intended to be intermittent therapies. These are therapies that patients are meant to initiate and stay on, unless there’s a reason the provider stops them from their therapy, or they’re having some health concern that they need to stop it. Because patients have become accustomed to using topical agents intermittently, they sometimes transfer that into systemic agents. We have to do a better job as practitioners of educating our patients on that.

The other part is helping patients know when it’s appropriate to hold their objections if they’re on a biologic agent to recognize those concerns, but it can be challenging sometimes to coordinate with the rheumatologist or their primary care provider. Being able to communicate effectively as a part of the care team, with the other individuals who are responsible for the patient, is another crucial part of the puzzle.For the biologic naïve, it’s ]approaching the patient understanding their comorbidities, understanding their concerns. Will they feel comfortable? Was the patient more comfortable with us giving the injection in clinic? Is this something that would not at all fit for their lifestyle? That’s the proper approach to helping the patient and having that discussion about the appropriate education for them.

®. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming 

® and other great content right in your in-box.

Stratification of patients for the treatment of plaque psoriasis based on comorbidities and prior biologic experience.

Stratifying Patients With Plaque Psoriasis for Treatment With Biologics

Matthew Brunner, MHS, PA-C, DFAAPA  

The last question that we should address is the following: How would you introduce the patient to the fact that they will be or could be taking a biosimilar? What type of discussion would you have with the patient?

 This is a great question, where we’ll have to come up with our ways of explaining a very complicated aspect to our patients in ways that are understandable and reassuring. I’ll be telling most of my patients that this is good news, that these products have been carefully tested and studied at a number of levels and their experience should basically be the same. The benefit of having these biosimilars available is that it should make the therapies more accessible to our patients because they’re so expensive.

It’s going to be challenging, though. With my own practice, we have so many options for psoriasis. I’ll often say, “We have to try biologic A,” and we agree on it. I send them the information on it and then the insurance company says, “No, it’s going to be biologic B.” Even when we agree it’s biologic A, they may be told it’s going to be biologic B and say, “But it isn’t the drug you told me.” It’s now this other thing with a different name they don’t recognize, and we have to go back and have that conversation. That’s likely to be a big source of anxiety for our patients. We know a lot of our patients are reluctant to go on biologics sometimes, so adding these additional complexities and barriers for our patients may cause harm in individuals who tend to be pretty reluctant or anxious about this process from the get-go.

It’s all about patient education, though. When I see a new patient with rheumatoid arthritis—it’s the easiest one—I can persuade 99% of patients to go on methotrexate for the first drug. It isn’t a big problem. Then when 70% of patients respond to methotrexate, and then we have all those other molecules available. I talk about all those molecules. You give the patient informed consent, which has gotten much more complex as time has gone on because there are many more drugs. Then I ask, “Which would you prefer first? Which would you prefer second?” In the end, I say, “Your insurance company is going to make the decision. I want to know what you’d do if the insurance company doesn’t pick your first choice.” They pick one. “What do we do if that one doesn’t work?” That’s how I handle that, and it usually works.

In speaking to a patient, you have to simplify, just as you did, that the biosimilars have shown that they’re very similar to the reference product and that almost all patients who will respond to a reference product will respond to a biosimilar. It’s that switch patient, the ones who do well, where I think there’s a little more angst. Even there, I’d say, “The literature shows that 95% of patients do well,” but I like to have the availability to switch back to the bio-original if I can.

 The critical thing for clinicians to know is the importance of instilling confidence, because the data give us the confidence that’s well earned. In my practice, when I choose mechanism of action A and then the insurance company says, “No, you have to use B,” as long as I think B is a very good option, I’ll go back to the patient and say, “The company wants you to use this biologic. It’s an outstanding option for you. It’s very likely to clear your skin, and I recommend it.” Almost all my patients in those settings are OK with that situation and are willing to make that switch. It should be an even easier thing to instill confidence when we’re staying within the same mechanism of action and a similar biologic. They should expect the same experience, whether we call it adalimumab or whatever the biosimilar name is going to be.

Thank you. To summarize, the prescribing physician has to have confidence in the biosimilar, and then the physician, the nurse practitioner, and all the ancillary personnel have to have that same degree of confidence. I can imagine a physician telling the patient, “There’s almost no difference between these drugs,” and then the infusion nurse or some laboratory person says, “I wouldn’t take a biosimilar.” Who’s the patient going to listen to? A well-educated physician or the laboratory tech? It’s going to be the lab tech.

 Or it might be social media. It might be what someone googles online or reads in a chatroom, where someone says, “I was doing OK on this, and I went on that, and now I’m having a problem.” As clinicians, we have to expect that there will be some uncertainty, and we’ll have to be there for our patients, empathize with them, and help them make the best decisions possible and move forward in a way that’s of best interest to their health.

presentation. We hope you found this presentation to be rich and informative.

Drs Roy M. Fleischmann and Joel M. Gelfand discuss addressing patient concerns to biosimilars and provide take-home messages to clinicians utilizing biosimilars.

Addressing Patients' Concerns With Biosimilars

Roy M. Fleischmann, MD

2025 American Academy of Allergy, Asthma, & Immunology (AAAAI)

 in San Diego, Scott Sicherer, MD, from Mt. Sinai School of Medicine, presented the 

, “Randomized Trial of High Dose, Home Measured Peanut Oral Immunotherapy in Children with High Threshold 

His team’s phase 2 trial compared the tolerance levels of peanut oral immunotherapy vs avoiding peanuts altogether in 73 children aged 4 – 11 years with a high threshold peanut allergy (> 143 mg) The study assessed whether patients on oral immunotherapy could tolerate 3400 mg of store-bought peanuts and then 9043 mg during the oral challenge.

100% of children on oral immunotherapy tolerated 9043 mg of peanuts, compared with 10% in the avoidant arm. 

 spoke with Sicherer at AAAAI 2025 about these promising findings.

: What prompted this research, and does it address a significant gap in peanut allergy management?

 All of the products that [the FDA has approved]—which are two omalizumab and also a commercial version of peanut oil immunotherapy—specifically brought people into the study if they reacted to half of a peanut or less. [This] makes sense because they're very sensitive to small amounts [and] more prone to have a reaction if there's a little bit of peanut in a cookie, a little mistake like that. But [these studies are] ignoring the half of the children who have a peanut allergy but could already eat half a peanut…who might be what we call “bite safe.”

[This group] could represent almost half of the peanut-allergic population. We figured that [they] would even be easier to treat, and maybe treatable with very simple measures, [such as] peanut butter. Something that you could just buy in the store…measure…[and] use as a medicine, except that obviously would have to be done under doctor supervision. That's what brought the study together.

: Your trial found that participants who underwent peanut oral immunotherapy had a significantly higher rate of desensitization compared to those who avoided peanuts. What are some of the key factors that contributed to this success, and what does this mean for the future of peanut allergy treatment?

 We randomized the group that was already identified as [having a] higher threshold, [meaning they could] eat more than half of the peanut before they would react. We randomized them to either go through this process of oral immunotherapy using home-measured amounts of peanut, but under allergy supervision versus [to] just avoid it.

The group that did not go through the…gradual increases under doctor supervision… had the same threshold at the end of the study. Some…actually showed a lower threshold than they started with. Some showed a higher threshold than they started with, but on average, they had no change. They were [often] still bite-safe, but they couldn't eat peanut butter.

For the ones who had the feeding test, all of [them] were able to eat a peanut butter and jelly sandwich worth of peanut butter—so they were basically able to eat it like regular food.

We wanted to also ask the question: is this a durable response? What would happen in real life if they stopped taking it as a daily dose? Because they were taking…a tablespoon a day as a daily dose as treatment? We had them spend 4 months eating it… so we encouraged them to have peanut butter and to hopefully have about two tablespoons a week, but we didn't give them a specific plan. We had them completely stop any peanut butter for 2 months so they wouldn't have any exposure. Then we brought them back to a feeding test, and for all the ones that came back for that feeding test, almost 90% were able to still ingest that whole peanut butter sandwich worth of peanut butter.

Typically, you would have said, “Oh, gee, you’re allergic to peanuts, don't eat it.” But with this information, you can make a very strong argument that if the family and child were interested in raising their threshold and eating the food more like regular food, although I would not call it a cure, it's still a treatment. They could go through a process that's relatively simple, not a lot of visits with the doctor, and could end up having them eat peanut butter like regular food.

Is there anything else you want to add about the findings?

 The starting point here is to determine [a] threshold. Is this person sensitive to tiny amounts or not? If you don't figure that out, you would never want to apply this particular protocol. Secondly, it's important to have allergist supervision. I do worry that people will look at this and say, ‘Oh, home measured, home purchase’ [and interpreting it could mean] you just do this all on your own, like you're a family. No, that could be risky and dangerous. You have the allergy. You have to work with an allergist if you're going to approach something like this.

Sicherer, S, Bunyavanich, S, Berin, C, et al. Randomized Trial of High Dose, Home Measured Peanut Oral Immunotherapy in Children with High Threshold Peanut Allergy Journal of Allergy and Clinical Immunology, Volume 155, Issue 2, AB445

Derman, C. Peanut Oral Immunotherapy Boosts Tolerance in Children with High-Threshold Peanut Allergy. HCPLive. March 3, 2025. 

https://www.hcplive.com/view/peanut-oral-immunotherapy-boosts-tolerance-children-high-threshold-peanut-allergy

A phase 2 trial presented at the 2025 AAAAI meeting explored high-dose, home-measured peanut oral immunotherapy in children with high-threshold peanut allergies. The study demonstrated that 100% of children undergoing oral immunotherapy tolerated 9043 mg of peanuts, compared to 10% in the avoidance group. The research addresses a gap in peanut allergy management by focusing on children who can already tolerate small amounts of peanuts. The findings suggest that oral immunotherapy could enable these children to consume peanuts like regular food, though allergist supervision is crucial.

A phase 2 trial found that 100% of children on peanut oral immunotherapy tolerated 9043 mg of peanuts, vs 10% in the avoidant group.

Oral Immunotherapy Shows Promise for High Threshold Peanut Allergy, with Scott Sicherer, MD

Scott Sicherer, MD, FAAAAI

Globally, an estimated 850 million and 64 million people live with some form of kidney disease and heart failure (HF), respectively. Patients with chronic conditions of HF, chronic kidney disease (CKD), and diabetes, as well as those taking certain medications like RAAS inhibitors, are at an increased risk of developing hyperkalemia (HK) - a higher-than-normal potassium level in the blood.

HK can be a chronic condition and has been associated with increased hospitalizations and death. In a US-based retrospective study from integrated health delivery networks, HK was found to be an independent risk factor for all-cause mortality in almost 1 million patients including those with CKD, HF, and/or diabetes.

 In a second US-based retrospective analysis of a medical claims database of 39,626 matched pairs of patients with or without HK, 40% of patients with HK experienced 2 or more hyperkalemic events during the 1-year post index period.

“It is important to take hyperkalemia seriously, as it is a potentially fatal condition,” says Pamela Kushner, MD, FAAFP, a primary care physician (PCP) and clinical professor at the University of California Irvine Medical Center. “People with CKD, and/or HF, or other cardio-renal comorbidities, if they are diagnosed with chronic hyperkalemia, they may need long-term management due to the underlying condition. As a PCP, I often support my patients with a diagnosis of hyperkalemia, and I make regular potassium monitoring a part of their long-term care plans as soon as possible.”

RAASi therapy are a group of medicines recommended by the 2021 European Society of Cardiology (ESC) and the 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America (AHA/ACC/HFSA) for the treatment of patients with HF. The 2022 and 2021 Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guidelines recommend the use of ACEi or ARB for the treatment of patients with CKD and hypertension with/or without diabetes.

Javed Butler, MD, MPH, MBA, a cardiologist at Baylor Scott and White Health in Dallas, Texas, and a professor of medicine at the University of Mississippi Medical Center in Jackson, Mississippi, explains, “RAASi therapy is one of the most important management approaches for HF patients. These lifesaving treatments reduce the number of HF-related hospitalizations and reduce mortality risk.”

Unfortunately, RAASi therapy has been associated with HK, which is often treated with a reduction or discontinuation of RAASi therapy. In a US-based medical records analysis of patients prescribed a RAASi, including ACE inhibitors, ARBs, direct renin inhibitors and select MRAs, mortality was at least 2x higher for patients with CKD whose RAASi had been reduced (20.3%) or discontinued (22.4%) compared to patients on maximum RAASi doses (9.8%).

Given the impact that HK can have on patients, a long-term and continued approach to treating HK is needed.

 diet is a non-therapeutic approach to managing HK, however, there is a lack of high-quality evidence demonstrating its effectiveness as a HK management strategy. A major contributor to HK in patients with advanced CKD is inadequate excretion of K

 through the kidneys, so reduction in dietary K

 alone may not be sufficient. In addition, a low K

 diet may deprive patients of important nutrients or could conflict with some aspects of a heart-healthy diet. Dietary modifications can be challenging to achieve and adhere to in patients with CKD as well.

There are several guideline recommended options for managing HK which include both therapeutic and non-therapeutic approaches.

According to one practice point from the 2021 KDIGO clinical practice guidelines for the management of blood pressure in CKD, HK associated with RASi use can often be managed by measures to reduce the serum K

 levels rather than decreasing dose or stopping RASi. Strategies to control chronic HK include dietary potassium restriction; discontinuation of potassium supplements, certain salt substitutes, and hyperkalemic drugs; adding potassium-wasting diuretics; and oral potassium binders. In CKD patients receiving RASi who develop HK, the latter can be controlled with newer oral K

 binders in many patients, with the effect that RASi can be continued at the recommended dose.

The 2022 KDIGO Clinical Practice Guideline for Diabetes Management in CKD recommends that treatment with an ACEi or ARB be initiated in patients with diabetes, hypertension, and albuminuria, and that these medications be titrated to the highest approved dose that is tolerated. Hyperkalemia associated with the use of an ACEi or ARB can often be managed by measures to reduce serum potassium levels rather than decreasing the dose or stopping the ACEi or ARB immediately. Measures to manage HK include: review concurrent drugs including over the counter and herbal drugs as well as supplements to avoid/discontinue drugs that impair K

 excretion, moderate potassium intake, and consider diuretics, sodium bicarbonate, and potassium binders. Potassium binders should be considered to decrease serum K

 levels after other measures have failed, rather than decreasing or discontinuing ACEi or ARB treatment.

Among patients with HF, the ESC 2021 guideline refers to the use of potassium binders for the treatment of acute and chronic HK in patients with HF which may allow initiation or uptitration of RAASi in patients with renal dysfunction or HK.

Rethinking Episodic Hyperkalemia Management in Support of Current Guideline Recommendations

HK can present as a single episode, but the reality for many patients with CKD is that their HK will, or already has, become a chronic condition. HK remains an ongoing threat in patients with comorbidities such as HF, CKD, and/or diabetes, as many within this patient population have recurrent HK episodes.

“Viewing hyperkalemia as a chronic or recurrent condition is an important step for patients and their care teams to ensure an optimal approach to ongoing management,” says Professor Kam Kalantar-Zadeh, MD, MPH, PhD. “There are guideline recommended ways for nephrologists and other clinicians to manage their patients’ hyperkalemia episodes over the long-term, which include options in addition to potassium restrictive diets, which may deprive patients of healthy fruits and vegetables, especially those with CKD.”

Physicians should take a guideline-informed approach when managing HK, including RAASi-associated HK, especially in patients with HF, CKD and/or diabetes.

*Retrospective study of 911,698 patients from multiple integrated health delivery networks (Humedica). Control group included 338,297 individuals without known HF, CKD, diabetes, cardiovascular disease, or hypertension. Patient data came from private insurers, Medicare and Medicaid users, and uninsured individuals.1

†Based on a retrospective analysis of a medical claims database with 39,626 matched pairs of patients with or without hyperkalemia. Patients with hyperkalemia were defined as having 2 laboratory tests with a serum potassium level >5.0 mEq/L, at least 1 diagnosis code corresponding to hyperkalemia (ICD-9-CM code: 276.7), or at least 1 prescription fill of SPS.3

‖Based on data from an analysis of medical records of patients 5 years and older with at least 2 serum K+ measurements from the Humedica database. Patients with ESRD at the index date were excluded from outcomes analyses. Patients were included if they had at least 1 outpatient prescription for a RAAS inhibitor, including ACE inhibitors, ARBs, direct renin inhibitors, and select MRAs. Patients were categorized by their last RAAS inhibitor dose level for the analysis of mortality, where maximum was defined as the labeled dose and submaximum was defined as any dose lower than the labeled dose. Mortality rates for the overall population (N=201,655) during the 12-month period were 4.1% for patients on maximum RAAS inhibitor dose, 8.2% for patients on submaximum dose, and 11.0% for patients who discontinued RAAS inhibitor therapy. Causality between RAAS inhibitor dose and adverse outcomes was not evaluated.4

Collins AJ, Pitt B, Reaven N, et al. Association of serum potassium with all-cause mortality in patients with and without heart failure, chronic kidney disease, and/or diabetes. Am J Nephrol. 2017;46(3):213-221

Betts KA, Woolley JM, Mu F, Xiang C, Tang W, Wu EQ. The cost of hyperkalemia in the United States. Kidney Int Rep. 2018;3(2):385-393

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Rethinking Hyperkalemia Management: A Practice Change Approach

Stephen Greene, MD, FACC, FHFSA 

0:50 Need for using older diabetes medications

3:30 Quick-release bromocriptine: benefits in T2D and cardiovascular risk

6:15 Efficacy of quick-release bromocriptine

8:10 Quick-release bromocriptine as monotherapy and as an add-on

9:00 Mechanism of quick-release bromocriptine

11:41 Titrating quick-release bromocriptine

22:30 Positioning older T2D therapies in the current treatment regimen

In this episode of MEDcast, the expert panelists examine some underutilized therapies in type 2 diabetes (T2D) and explore their potential as effective treatment choices for many patients.

Authors