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Improving Outcomes in CKM Syndrome: Alinging Clinical Guidelines With Patient-Centered Care

Dr Jay Wish (Indiana University School of Medicine): Here we have what we are calling our Smart Patient CKM online group. This was 92 respondents that participated in a focus group. Some of the information that I will be presenting in the next 2 slides was the result of the patient input into this focus group. At this time, I would like to introduce my cofaculty member today, who is a patient advocate. She is Gail Balch. She lives in Tacoma, Washington. She is, of course, very familiar with some of these issues because she actually cares for her husband, who has cardio kidney metabolic syndrome, and is familiar with a lot of these medical issues, as well as some of the logistical challenges in getting her patient the best possible care. Welcome, Gail.

Gail Balch: Hi. Thanks for having me.

[00:10:43]

Smart Patients Speak: Communicating Rationale and Benefit in Complex Regimens

Dr Wish: What did the Patient Focus Group come up with? You can see some of the issues that were raised by the group. There are a lot of bullet points here, and we do not have time to go through every one of them, but we can talk top line in terms of categories. There was communication about safety monitoring and adverse events. There was respect and rationale in the dialogue. Quality of life and shared decision making gaps. Communication about the rationale for new or complex treatment. The 1 issue that seemed to be the most concern, as you can see, for 42% of the patients, was that they are just not getting the information that they wanted regarding why a new medicine was needed. What was the rationale? What were the expectations? How was the new medicine going to change their course vs doing what they were doing already. I would like to call on Gail to comment on that perspective.

Gail Balch: We have just had not as good of luck with physicians and specialty people that tell us what the medication is for. They say, "You need to start this. It will do this," but they do not give us the whys and wherefores behind it. They also have not been giving any, “if you are on this, it would not be a good idea” type of thing. It has been difficult getting information.

Dr Wish: Do you find that the provider does not answer the question? Do you think that it is an uncomfortable environment to bring the question up even in the first place? Or do you think when they answer the question, it is not in the English terms that you can understand? Is it maybe too technical, too medical jargon?

Gail Balch: I think they do not know how to dumb it down. That might be a crass statement, but there are a lot of people out there who do not understand the medical lingo to the point that say, I do. I'm very fortunate that I have got a little bit of a medical background, so I find that they seem to have difficulty in being able to not talk medical lingo.

Dr Wish: Okay. Thank you. That is a very important perspective, and I am glad you can share that with us.

[00:13:11]

Aligning Clinical Guidelines With Patient Centered Approached in CKM Care

Let us talk about aligning clinical guidelines with a patient centered approach to care and cardio kidney metabolic syndrome. This is the definition of cardio kidney metabolic syndrome. You can see it is an interlinked disorder of obesity, diabetes, chronic kidney disease, and cardiovascular disease across at risk and established cases. It is extremely prevalent. You can see the global prevalence 700 million people, about 40% overlap with type 2 diabetes and cardiovascular disease. Heart failure prevalence being about 64 million, 50% of whom also have CKD. Of course, obesity is an important driver for this syndrome. The end organ dysfunction that occurs in terms of cardiac disease, kidney disease, and diabetes, and the residual risk in heart failure despite goal-directed medical therapy, the events remain high.

[00:14:07]

CKM Syndrome Definition

You can see the stages of cardio kidney metabolic syndrome. For those of you who take care of heart failure, there is heart failure stages. For those of you who take care of patients with kidney disease, there is kidney disease stages. Here we have a staging mechanism for cardio kidney metabolic. Given the constraints of time, I am not going to go through all those individual points.

[00:14:29]

Interdependent Pathophysiology of DM, CKM, and HF

The interdependent pathophysiology you can see in this diagram, the various organs and how they talk to each other. Perhaps some of that talk becomes dysfunctional because of the overall adverse metabolic environment. If you want to start with any particular organ here, and it is a complicated slide, you can see over on the left hand side, you have the heart, you have sympathetic nervous system and RAS system, over activation, chronic inflammation, cardiovascular dysfunction leading to low cardiac output, decreased renal perfusion, sodium and water retention, and overstimulation of the RAS system.

Uremic toxins again, inflammation rearing its ugly head, and then metabolic dysfunction in terms of the effects of the obesity, the diabetes, hyperglycemia, beta cell dysfunction, etc. It becomes a vicious cycle where all of these organs become dysfunctional. If you can see, there is a common denominator of the inflammatory aspect of this environment that also accelerates the organ dysfunction and ultimately leads to symptoms.

[00:15:40]

Stages of CKM Syndrome

The stages we talked about very briefly in a previous slide. Stage zero would be no risk factors. Stage 1 is where you start to see the obesity excess adipose tissue. Stage 2 is where you have the metabolic risk factors in terms of the hypertension, hypertriglyceridemia, type 2 diabetes, and chronic kidney disease. Stage 3 you have the subclinical cardiovascular disease, especially subclinical heart failure. Then stage 4 you have the full blown end organ changes of each of these systems with heart failure, chronic kidney disease, atrial fibrillation, stroke, etc. There are a number of subclinical cardiovascular disease risk equivalents that can also act as surrogates for demonstrating the end organ changes of this adverse metabolic environment. Now, these are very, very busy slides. We again, do not have the time to do a deep dive into them. I am going to do a top line here.

[00:16:40]

Stage 1-3 CKM Syndrome: Management Algorithm

As you can see again stage 1 excess adipose tissue. Stage 2 is where you have the established risk factors. Stage 3, the subclinical, and again you can scan each of these boxes to show all of the possible manifestations in metabolic adverse events that occur.

[00:16:58]

Stage 4 CKM Syndrome: Management Algorithm

Then moving to stage 4. Here's a management algorithm that has been proposed in terms of addressing each of these subcomponents the dysfunctional adiposity, the CKM risk factors, etc, as atherosclerotic cardiovascular disease, hypertriglyceridemia, hypertension, CKD. It is important, again, when we talk about these things with our patients, to get them on board by understanding that early intervention is going to have the greatest effect in changing that risk trajectory. That this is a progressive disease. It is a multiorgan system disease, and the earlier we can get in and do some intervention, the more likely it is that we are going to change the trajectory and ultimately delay outcomes, if not decrease the outcomes altogether.

[00:17:49]

KDIGO Health Map for CKD

This is what is called a heat map. Many of you who take care of patients with chronic kidney disease are familiar with it. On the vertical axis is the stage of the glomerular dysfunction stage G1, G2, G3, etc, and then on the horizontal axis is the level of proteinuria. The first column is microalbuminuria, or I should say the first column is no albuminuria. The second column is microalbuminuria between 330 and 300, and then the third column is severe or macroalbuminuria. What you can see here is that you move from left to right to greater levels of proteinuria at any stage of GFR. It becomes higher risk for progression of chronic kidney disease, but also again, because the chronic kidney disease, the cardiovascular disease, and the metabolic disease is all linked, then you are moving to a higher risk state for basically all of these end organ changes. We like to push the patients into that upper left hand corner where they are at the lowest risk, minimal albuminuria, lowest level of GFR dysfunction, and hopefully keep them there for as long as possible with the interventions that we have at our disposal.

[00:19:06]

CKM Burden and Care Fragmentation

Let us talk a little bit about care fragmentation, because again, the patient groups have let us know that this is 1 of the main barriers to what they feel is the most effective care, that their providers are not talking to each other. They are not communicating. They go to a clinic visit with the nephrologist, and the nephrologist is totally unaware of what happened with the cardiologist or with the endocrinologist, etc. This fragmentation cannot only lead to missed opportunities for care, but can now also pose the risk for a duplication of care; that 1 provider is prescribing a drug that may have an adverse interaction with a drug that is being prescribed by another provider. CKM multimorbidity significantly increases the risk of heart failure, hospitalizations, cardiovascular death. 40% of patients with type 2 diabetes and 50% of patients with cardiovascular disease have comorbid chronic kidney disease. This is a very, very common phenomenon where these patients are seeing multiple providers. Overweight increases twice and obesity increases 4 times for developing cardio kidney multimorbidity. We talked about the fragmented care, the patients often face polypharmacy, conflicting care priorities. Unfortunately, because of this poor communication environment, few patients receive all of their indicated therapies. Because, in many cases, each provider is depending upon another provider to institute that particular aspect of their care and then ultimately no provider does it, or there is duplication.

[00:20:46]

Guideline-Concordant Therapy Pathways

This is guideline-concordant therapy pathways. We know now that SGLT2 inhibitors are pretty much good for everything. This is obviously an evolution in our understanding of the benefits of this class of drugs. First, they were just for diabetes, and then we realized that they decreased proteinuria. Then we realized that they are good for patients with chronic kidney disease, even in the absence of proteinuria. Then we realized that they are also good for patients with heart failure. As far as I am concerned, SGLT2 inhibitors should probably be in the drinking water, but they are not. They have to be prescribed. Many of them are very expensive, and there are a lot of prescription drug plans, that pose very high copay barriers to SGLT2 inhibitors. It is often a challenge to the medical practice to navigate those barriers and figuring out which SGLT2 inhibitor is favored by that prescription drug plan. Sometimes, we have to be somewhat creative in terms of prior-authorization as well as patient support options.

GLP-1 receptor agonists are recommended for reducing atherosclerotic cardiovascular disease management as well as weight management. As you know, we are now seeing more of these coming into the weight management space, where they again, were initially primarily for diabetes control. Finerenone, which is a nonsteroidal mineralocorticoid receptor antagonist, like spironolactone, only nonsteroidal, has multiple benefits. It has been actually shown to have incremental value in terms of improving outcomes in patients already receiving SGLT2 inhibitors, ACE inhibitors, angiotensin receptor blockers and GLP-1 RAs. RAAS inhibitor therapies, of course, are standards of care for heart failure, for diabetes, and for proteinuria and for hypertension. The statins, of course, make up the baseline therapy for atherosclerotic cardiovascular disease and chronic kidney disease. They are now considered standard of care for patients with CKD, even in the absence of high cholesterol levels because of the benefits in terms of inflammation. Again, the lower your LDL, probably the better.

[00:23:13]

Underuse of Evidence-Based Therapies

What are we dealing with in terms of opportunities for improvement? We know that these evidence-based therapies are underused. Of those with a class 1A recommendation, those are the recommendations that have the strongest evidence base, only 11.9% of patients with type 2 diabetes, and 3.1% of patients without type 2 diabetes were prescribed an SGLT2 inhibitor. Again, many reasons for this. Again, high copays, perhaps unawareness of the benefits and all of these aspects of care, as I said, probably should be in the drinking water. Again, each provider thinking that it is going to be the other provider that is going to actually do the prescribing. Less than 10% of patients with atherosclerotic cardiovascular disease are treated with GLP-1s. Less than 36% of heart failure patients receive an MRA, either a steroidal or nonsteroidal. Again, the reasons for this underuse are cost, the silos of communication, and then clinical inertia. "Oh, you are doing fine." Even though we know there is things that we can do that may make your outcome better. You have not had an event yet, so we will just see how things go. That is probably not the way we want to work here.

[00:24:27]

Patient Case 1: Patient With Obesity, T2D, ASCVD

Let us go back to patient 1. The patient recently relocated and presents at their primary care office. Past medical history: diabetes, obesity, atherosclerotic cardiovascular disease with a prior MI. Recent labs that are A1C is way poorly controlled at 8.1%. eGFR 49 puts them in stage 3B, and you can see albumin-creatinine ratio in the microalbuminuria range. Lots of opportunities here for improvement, better glycemic control, perhaps improvement in GFR and perhaps reduction in proteinuria. Their current medications: metformin, linagliptin, lisinopril, atorvastatin, and ASA.

[00:25:15]

Poll 3

Next question is what therapy would you prioritize for initiating today in your office?

A. Adding GLP-1 RAs, example semaglutide;

B. Adding an SGLT2 inhibitor, example empagliflozin;

C. Adding a nonsteroidal MRA, example, while actually finerenone being the only one that is approved at this point; or

D. Just continuing their current regimen monitor for now, and perhaps waiting until they end up in the hospital with some complication to decide to change course.

Go ahead and enter your response.

Speaker 3: Polling is open. Please vote. I will give a few more seconds for incoming replies. All right I will go ahead and close that poll.

Dr Wish: I see GLP-1 RA has the highest number of votes, 40%. SGLT2 30%. Nonsteroidal MRA 30%, or continue current regimen zero. That is reassuring that everybody realizes this patient is not doing well with the status quo, and that something needs to be added. Again, I think this is probably a matter of opinion, whether you would go with a GLP-1 RA or an SGLT2 inhibitor. I think many patients or I think many providers, would probably make that decision based on perhaps how overweight the patient is, getting the additional benefit of the GLP-1 RA weight reduction, or if the patient is not severely overweight, perhaps going with SGLT2. The SGLT2 has the advantage of being oral. The GLP-1 at least for glycemic control is an injection. Again, this may require some discussion with the patient in terms of what they are going to buy into. Let me ask Gail, in terms of this particular scenario. Choosing a GLP-1 RA vs an SGLT2 injection vs oral, do you think there is going to be patient pushback for favoring the oral vs the injection?

Gail Balch: Definitely. People are scared to death of needles. Even from just talking with other individuals in different scenarios, they even cannot give themselves injections. They will have a spouse or a child do it.

Dr Wish: That would be a good reason to favor going with the SGLT2 first and then the GLP RA second. Again, I think unless they were morbidly obese or severely overweight, and we felt that was the major barrier in terms of glycemic control, blood pressure control, etc, and then we might favor the weight reduction feature of the GLP-1 over the SGLT2. They all have beneficial effects on glycemic control. They all have beneficial effects on heart failure. They all have beneficial effects on proteinuria, so that is really not a major distinguishing characteristic. The major choice here would be the injectable vs the non-injectable, and the obese vs the non-obese patient. Do you agree with that, Gail?

Gail Balch: Yes.

[00:28:38]

Poll 4

Dr Wish: Poll 4. When would you initiate additional therapy for this patient?

A. Immediately during today's visit;

B. After confirming repeat labs;

C. After referral to your colleagues in nephrology, cardiology or endocrinology; or

D. Only if symptoms progress;

Go ahead and enter your response.

Speaker 3: Polling is open. Please vote. I will give a few more seconds for incoming replies. We will go ahead and close that poll and share.

Dr Wish: Immediately and after confirming today's labs are neck and neck at about half of the responses. My recommendation would be no time like the present. We had relatively recent labs. There is no reason to think, without any change in the patient's therapy since the last labs were drawn, that their A1C is going to be any different, that their GFR or albuminuria level is going to be much different, because there was no change following the last set of labs. My inclination would be to go ahead and start at today's visit, explaining what you are doing, basically telling the patient, "We are going to do this. We are going to maybe confirm your labs today or maybe not even confirm the labs today and wait till your next visit to see what the effect of this intervention is, and then decide whether or not we are on the right track."

[00:30:16]

Poll 5

What most often delays therapy initiation for patients like this in your practice? Is it

A. Cost/insurance;

B. Concern about polypharmacy and side effects;

C. Not sure who owns the prescribing; or

D. Patient hesitancy or adherence issues;

I do not think there is any real single best answer here. I think all of these play a role and some play more of a role in some practices than others, and some play more of a role in some patients than in others. What we are asking for here is in your particular practice, in your particular patient population, which perhaps is the greatest barrier. Go ahead and enter your answer.

Speaker 3: Polling is open. Please vote. We will give a few more seconds for incoming replies. We will go ahead and close that poll.

Dr Wish: I see by far and away, cost and insurance access is the number 1 answer, 82%. I agree, this is probably the biggest issue in my own practice. I practice in an inner city. Most of my patients have very, very poor insurance. Even those patients who have a prescription drug plan, the co-pays on things like SGLT2 inhibitors or GLP-1 agonists are prohibitively high. As soon as the patient finds out the sticker shock, they basically say, "No thanks. Cannot afford it. I'm not going to starve my family to take this medicine, even if I agree that it is probably the best thing for me at this particular time."

[00:31:57]

Key Teaching Points for Patient Case 1

Key teaching points for patient 1. Again, I do not think we need to go through each of these individually, but on the right hand side of the slide, I think it is important to see some of the large scale, very well-designed clinical trials that were done that show the benefits of these classes of drugs. The EMPA-KIDNEY improvement in risk progressions with empagliflozin. With the FLOW study, semaglutide again, kidney disease events, advanced cardiovascular death. The FIDELIO and FIGARO DKD finerenone decreased CKD progression and cardiovascular effects. The DAPA-HF deliver SGLT2 inhibitor benefit across the heart failure spectrum, and the STRONG-HF rapid initiation of disease modifying therapy and include heart failure, improves quality of life, and reduces the risk of 180 day heart failure readmission, as well as all cause death. These are strong evidence bases for the recommendations for the use of these drugs in the patients that we are talking about today.

[00:33:06]

Get Ready to Interact!

Get ready to interact. Our patient will have an opportunity to do a real talk, sharing their real life experience. Please submit questions, comments, and your own examples in the chat and we will review what the learners, you guys in the audience, submit during this mini-Q&A.

[00:33:28]

Quick Connect Q&A

All right. Questions for our patients or our patient advocate today. You have this slide. You can tell us in terms of your care of your husband, because you are not the patient you are the patient advocate. Which of these issues drives perhaps a lot of what you do for your husband in terms of improving, their care?

Gail Balch: [00:33:53] The CKD drives us every single day because our life revolves around dialysis. Now, I will admit that my husband is 18 years older than I am, and he has a different perspective on living and how he wants to live the rest of his life. As a younger person, I would tend to take more steps to keep going. He is at the point he wants to enjoy his life. When it comes to a new medication, insurance definitely matters a lot with what they are going to pay. Giving a medication is not so much a problem with us, because I can handle needles with absolutely no problem. He does well also. The polypharmacy is an issue because A, he hates taking medications. If he can get away with it and survive just fine, that is his attitude. Yes, our HCP has started multiple medications, but they tended to be normal everyday type of things. It would be a statin along with something else that would be normal for controlling LDLs, HDLs, that kind of thing. As a patient advocate, no, I do not think the HCP's have shared decision making with him, other than to say, "This is a drug that we would recommend. Do you want to take it? How do you feel about that?" It has been pretty much the care providers, making the decisions for him, even as the disease has progressed over 30 years.

Dr Wish: Let me ask, is being on dialysis is a special case because the silo of dialysis is somewhat more compartmentalized than being in, say, a hospital system where you are going to a clinician's office, and they are using the same EMR as all the other clinicians that are taking care of the patient. A dialysis corporation like a DaVita or Fresenius, they have their own EMR. That EMR is not necessarily shared with the local hospital system, where the patient gets their other specialty care. Do you find that is a barrier in terms of communication?

Gail Balch: Absolutely, without a shadow of a doubt. We constantly cannot get them to send, even though there has been a doctor's order, we cannot get them to send any of the blood works to the care providers. I have to take it every single time I get it. The medications. There are certain medications that the dialysis center will provide my husband, that for a while I did not even know he was getting. Then one day Steve came home and said, "Hey, by the way, I'm getting this pill." I went, "What pill?" He goes, "I do not know," because he cannot remember. They never contacted me.

Dr Wish: That is a very good example of the barriers that you and your husband are dealing with. I think this is representative of what is going on in a lot of patient situations. It is unfortunate that these silos continue to exist because the fact that your husband is on dialysis does not protect him from the other complications of CKM. The number 1 cause of death and hospitalization among dialysis patients is not their kidney failure, it is cardiovascular disease complications, heart failure, MI, stroke, etc. It is very, very important that these issues be addressed more effectively. Thank you for sharing.