[00:00:02] Introduction: Welcome to All Cats Considered, a podcast from the Feline Veterinary Medical Association.
Here we interview professionals from across the veterinary world and take deep dives into the latest evidence based research, developments, studies and guidelines that improve feline health and well being.
We are the home for veterinary professionals seeking to enhance the care of cats through high standards of practice, continuing education and evidence based medicine. In each episode you'll hear interviews with a variety of experts in our field covering a wide range of topics and the latest developments in feline health. We'll share the key points you need to know to improve your patients care.
Let's dive in and listen to this week's experts.
[00:00:45] Dr. St Denis: Hi, I'm Dr. Kelly St. Denis, Journal Co editor for the Journal of Feline Medicine and Surgery and JFMS Open Reports.
I am here today with the lead author in our latest Clinical Spotlight article, "Use of pimobendan in a practical evidence-based review."
Dr. Sonya Gordon is with me. Dr. Gordon, thank you so much for joining us today. And thank you to you and your co-authors for such an amazing Clinical Spotlight article.
[00:01:12] Dr. Gordan: It was, I mean, it's always a pleasure to work with your colleagues, but it's really fun when you kind of get to dive a little deeper into a topic that I think we're all practicing every day. I mean, we, you know, so we all treat cats with heart failure and it's fun to talk with your colleagues about how they're doing it and then go deep into the literature to see what it really has to say.
[00:01:33] Dr. St. Denis: Yes, as we've discussed, has been like a really interesting conversation around pimobendan because it has been around for use in dogs for some time now and it's not used extensively in the feline species. So obviously you and your co-authors as well as the two feline societies and the editors of the journal felt that this was an important topic of conversation.
What do you generally think is the role that this is going to play as a resource for veterinarians in general clinical practice?
[00:02:01] Dr. Gordan: I think right now there's sporadic publications and some of them are very research-y, you know, normal cats and drug dosing. And I think this is kind of like one stop shopping if you want to see what's been done to date.
And it's sort of put into one place. There's a nice table that lists all the publications and it sort of says what the publication was about.
So it really is pretty comprehensive, so it's nice for that. And then I think the pearl for a primary care veterinarian is that we tried to give voice to them. You know, we tried to. We didn't write a paper that was for us. We wrote a paper that was for them and tried to address what we believe is an unmet need, which is talking about this with primary care veterinarians.
[00:02:45] Dr. St. Denis: Yes. And that's super valuable. And I want to talk about that table in a little bit, too, because it is quite thorough and amazing.
And you sort of alluded. We don't really talk about pimobendan a lot. And there seem to be widely differing opinions regarding the use of pimobendan in cats, its efficacy, safety.
And I wonder if we can just touch on some of the concerns or even controversies that surround its use or application in the feline species.
[00:03:11] Dr. Gordan: I think the most obvious concern or starting point would be that we have a species that has a disease that is characterized mostly by thick heart walls that apparently squeeze quite well. Right. Like good contractility. And pimobendan is an inotrope.
You know, it strengthens the heart muscle. And it's hard on the surface to see how that might play a role.
So that I think that initial part of, like, how is it possible this could play a role in. Is probably one of the controversies.
[00:03:42] Dr. St. Denis: and that's certainly one of the most common diseases, I guess, that we see in cats is hypertrophic cardiomyopathy (HCM). So it's going to be problematic. But I guess what we're understanding is that this application is for congestive heart failure. So what sort of application would we use if we have a cat that's got congestive heart failure (CHF), is it regardless of the cause of the heart failure, are the limitations to the use, like, depending on the diagnosis? So if someone in clinical practice has a cat with congestive heart failure, do they need to have a diagnosis of the cause before they can even consider using something like Pimobendan?
[00:04:16] Dr. Gordan: So I think, you know, we've for a long time used drugs like Lasix when we have a clear index of suspicion that they have heart failure. And sometimes we're wrong. Sometimes the treatment or the lack of efficacy of the treatment clinically tells us that maybe we made the wrong choice. So I think it's. We know that we use drugs that don't have.
We don't always have a for sure diagnosis. Medicine is acceptable uncertainty.
Having said that, you would, you know, it is really a drug that if we're going to use it in the cat, we're kind of already trying to take advantage of some of its other properties, like the fact that it can maybe improve relaxation of these thick hearts. It might strengthen the contractility of the actual atrium, which tends to get dilated in these cats and not squeeze well and puts them at risk for thrombus as well as heart failure. Um, and. And then at the same time, as long as a little afterload reduction is tolerated. Right, lower resistance downstream, maybe that does make it more ideally or optimizes forward cardiac output. So I think there's a constellation of things that, you know, it's not really just about the fact that everybody thinks of Pimobendon is an inotrope, but it actually has a lot of other things that might benefit in the setting. Heart failure. And, and it's not just obviously heart failure characterized by obvious weak pumps, you know, where the heart is not squeezed. And that's an obvious indication but that the rarity in cats and requires echo to diagnose. And so I think it's really about how do you leverage this medication in the right situation clinically. And I think for me, I would say I fit in the middle of the pack. And I think as we wrote this, we kind of all did that. We believe there's clear indications and then there's probably some that are a little more gray zone. And we used clinical studies or little case vignettes in the paper to try to sort of show those off a bit. But for the easiest way to say it would be if you're. If you're treating a cat and I really feel like this, if you're treating a cat with heart failure and he's not doing well on standard treatment, he may never get an echo, by the way, but he's, you know, he's getting Lasix and his pleural effusion keeps coming back. Or he's even got large volume pleural effusion at the outset and he doesn't tolerate the high diuretic doses, you know. And so I think as soon as you tell me things that I normally do are not working well and the patient continues to have morbid associations with that so recurrence of pleural effusion or edema. I think as a rescue treatment, you have little to lose. I mean, I think the safety part of this drug is fairly. Although we might not be able to prove efficacy outright. I think the safety part I'm pretty comfortable with in most cats as a rescue, it's a great choice right now when you're failing other things as a first, but as a first line, that's where people get a little twitchy yeah.
[00:07:05] Dr. St. Denis: Yeah.
[00:07:06] Dr. Gordan: You know, the cat that comes in and you're pretty sure he's in heart failure, and yet he responds beautifully to one or two doses of Lasix, like many of them do.
Maybe that cat doesn't need pimobendan yet.
[00:07:17] Dr. St. Denis: So as a rescue treatment, then, and some of these cases, I've noticed, like, it's with client awareness that you're using something that is a rescue treatment that may or may not be effective, presumably not necessarily harmful, though, is that. Would you say? That's correct. Unless we have certain situations happening with the heart.
[00:07:35] Dr. Gordan: Yeah. I mean, I think, like I said, the safety data is pretty good. The concern around safety would be that if you take a heart and make it squeeze harder and it's already squeezing well anyway, the contractility is good and you make it hybrid dynamic.
Can you exacerbate or even cause obstruction of the type we see in cats with hypertrophic cardiomyopathy? So the obstructive form where they have abnormal mitral valve motion, systolic anterior motion of the mitral valve, or they even have a segment of their wall at the base of their heart. There's, you know, at the base of the septum there that's quite thick. As soon as you make them squeeze excessively, perhaps you can exacerbate that. So that's the concern.
The problem is it's hard, I think, if you echo a cat and you show that he has that obstruction, you know, he can do it. But it's very hard to rule it out in any given cat because it's situational. And that's why cats can have murmurs that are louder and softer, or one of the reasons they can have murmurs that are louder and softer. So if you're being the safety person and you're like, you want some ability to assess this cat is tolerating the drug. It's. It's easy to do by measuring a blood pressure after you dose them or a few days after and listening to see if the mermaid murmur gets louder or a new murmur develops. But I think if they tolerate it and they don't show any tachycardia or new murmurs that are louder or I think you should have confidence in the chronic dosing, at least, like I said, with the safety. And there are many of these retrospective studies that we talked about that have people reported using it do include cats that have had obstruction and a primary hypertrophic phenotype. And so. And they certainly didn't seem to show any adverse effects. But that is the concern that surrounds this. That's sort of that conundrum that. That controversy kind of.
[00:09:22] Dr. St. Denis: And if you don't have the information, I appreciate that you discussing that because were before we started recording our podcast. Today we're discussing how echocardiogram is not available for everyone. I live in Northern Ontario. We don't have a cardiologist at hand and not everyone can go for referrals. So sometimes we're kind of basing it on pocus or no echocardiogram or ultrasound of the heart at all. So I appreciate sort of that list of things that you would be looking for if you were going to try to use it to see if it was making things worse. So heart rate, blood pressure
[00:09:55] Dr. Gordan: murmur. Yeah, yeah.
[00:09:57] Dr. St. Denis: Okay. That's really good. I really thank you for explaining. And it tracks.
[00:10:00] Dr. Gordan: And because of the. We know enough about dosing that the oral dose is available you quite quickly. So if you were quite nervous, you could literally give the first dose in the hospital and before you release them, relisten, you know, and I don't believe that a single dose is going to be, you know, detrimental anyway. So if that's your concern, it's easy to a couple hours, two, three hours after the first oral dose to listen and if you're really worried, measure blood pressure and such.
[00:10:30] Dr. St. Denis: So you were talking about the research and the table that you guys have presented here, which I really appreciate. And I think there seems to be some limitation in the research around pimobendan. Like you mentioned, we have pretty good pharmacological data. So I wonder if you could talk a little bit about that. Like it's a bit different the way cats absorb this drug than dogs and we end up with an assumed dosage for them.
[00:10:54] Dr. Gordan: Yeah. So there's many people have tried to look at the kinetics and dynamics of this drug in cats. And then metabolism, not surprisingly, is different in cats. And we know that pimobendan's efficacy in the dog is related to the first metabolite.
And there's just difference in them, of course. Like all kinetic studies, they all seem to be done in normal animals. Yeah. And that's the nature of all the drugs, by the way. The safety data on that kind of stuff is always done in normal.
And then, you know, some of the pharmacodynamics people have looked at cats that have had modest forms of disease and seeing if anything, but most of it is in normal.
And so I think we know it's absorbed and it does have effect which effects are quantifiable. Because these are all small populations as well.
Does it really make the atria squeeze better?
Frankly, is measuring the contractility of atria something that's easy enough to do, that you can get a precise measurement that proves that in a conscious cat?
So there are other challenges associated with that and like investigating relaxation patterns in hearts and cats. Also not simple. Right. So I think part of it is our assessment tools may not be precise enough to show us some of these effects. And I'm a clinical trialist at heart, which means to me, you have a reasonable expectation of efficacy and a safety profile that supports the use of the drug in species. And then you ask a well designed, pragmatic clinical trial question that's powered adequately to answer the study and long enough term to answer the question.
[00:12:30] Dr. St. Denis: Right.
[00:12:30] Dr. Gordan: And that's what we're missing. We have a short-term prospective study that was six months, but it's prospective and it's randomized and. But it was short. And I don't know that six months is long enough to let the two paths diverge completely or not, as the case may be, because a lot of cats live for quite some time with heart failure. And remember, we're talking about heart failure right now. We are not talking about giving this to cats that are not sick.
[00:12:53] Dr. St. Denis: Right.
[00:12:54] Dr. Gordan: No part of me has any desire, nor have I ever given Pimobendan to a cat that does not have heart failure.
So just. So need for the Lasix. Okay, good.
Just to make sure. But ultimately, I think that we have large retrospective cohorts that have been described and some have even tried to have matching populations. But retrospective is hypothesis generating, not hypothesis proving. And so that's why there are. There can be two sides to how people think about this right now, because there's those who want the absolute truth to be 100% certain. And cat practitioners have to know that you would have no drugs to use hardly
[00:13:34] Dr. St. Denis: with a prospective study or a retrospective studies. And then also, as you mentioned, the study numbers. But I also noticed in some of those studies, like they treated the cat once and then checked the echocardiogram and velocities and such, and then that's it. Right. So that doesn't really tell us very much about how the drug works. It tells us one window in time.
[00:13:57] Dr. Gordan: Yeah. And really the endpoints that matter to me as long as there's no safety considerations are more pragmatic, like does it change the time to. Or the frequency of getting an ate a thromboembolism, because you Squeeze your atria better and maybe your platelets are a little less, you know, active. So I think there's, there's or don't get as sticky. So there's things about Pimobendan that make you wonder could it. But that's just a could it that doesn't prove, you know, then you'd have to have again inadequately powered with enough follow up. Just like with heart failure. Can you change when the cat becomes refractory to Lasix or could you. Is it, is it Lasix sparing? Does it mean that we can manage cats with less Lasix and a lot of cats with heart failure are older cats and have kidney. And Pimobendan certainly has no negative impact on the kidney that we're aware of. Right. In fact that's one of the nice things. It probably offers better forward cardiac output and it's not unlike RAS inhibitors where you have to worry that it helps and it works, but it might actually impact right negatively. So I don't know. I think it's still open for debate. And whenever you have mixed data and limited data, people are always left a little bit to their own conclusions. We hope we gave a balanced presentation in the paper that helped people decide for themselves where they land on it. Staying within the. I don't know, I'd call it the safety guidelines. Like don't. Well, cats.
[00:15:30] Dr. St. Denis: Yes, exactly. So on the topic of like you're mentioning other drugs that get administered to cats and heart failure, do we have many studies in terms of understanding how Pimobendan might interact with some of those drugs like the diuretics, antiplatelet drugs, dobutamine.
Do we have concerns about interactions with those other drugs?
[00:15:48] Dr. Gordan: I don't think you need to be.
I think that. Well, I mean we don't use dobutamine very often in cats. If you need dobutamine, that's probably more of a short term dog. They've been combined and used at the same time for supportive measures. But I think that would be a very unusual indication. Furosemide-wise like I said, maybe you even in theory need less Lasix or chronically use Lasix less because your heart is supported better. You know, you wouldn't know that from. But, but certainly they're used together all the time and they make sense because you. pimobendan's not going to get rid of that extra plasma volume. Right. You need, you need to get rid of some sodium and have water follow if you've got too much circulating plasma volume and just hopefully that the driving Factors telling your body to preserve that extra volume maybe are reduced by making the heart more efficient as an organ with a hemodynamic drug like Vetmedin or pimobendan. The ACE inhibitors, again, I don't have a negative interaction for those, although they're both, in theory, afterload reducers. Right. They're modest.
We're not going to get. Dropped their blood pressure, you know what I mean? It's. Yeah, so they're both. So I don't think you get dramatic reductions in systolic blood pressure with an ACE inhibitor in any case. Right. So I don't think there's a.
[00:17:03] Dr. St. Denis: Not in cats.
[00:17:04] Dr. Gordan: Not a concern there. I don't think that's a concern. Sometimes we worry about combining drugs that have a similar property, but. But they're both so modest at that effect. We don't need to worry about it. Spironolactone is another drug that's used in cats. Again, nothing to worry about there as an interaction. So I, I don't, I don't have anything that sort of comes to mind as a problem, especially in the kinds of drugs that we use. Platelet inhibitors are. Are still indicated, obviously, for any cat with a big left atrium, Even a cat that Perhaps is a B2 cat, you know, prior to.
That's one of those things that if we could do nothing but, you know, delay the first event for thromboem, prevent it would be great, but even delay it, that would be spectacular. Yes. And so we know that there are size criteria that indicate a cat has a high risk. And I don't think I can prevent heart failure, but maybe we could do something about that. And it makes sense because Pilobendan may reduce the stickiness of platelets, but you're not gonna hang your hat on that. That would be just an answer. Helpful property. I think we need to address ate on its own, on its own level and be aggressive at that.
[00:18:16] Dr. St. Denis: Yes, absolutely. And so as a phosphodiesterase inhibitor, it's not something that we'd be concerned about either. With reduced platelet aggregation as an actual problem for the cat, it'd be a plus.
[00:18:27] Dr. Gordan: It'd be like, bring it, bring it on. Let's. Let's get. Because their platelets are too darn sticky. Not that anybody's been able to document that. And I think, again, the problem is that the precision of what we're using to measure platelet aggregation and cat. It's challenging to do on normal cats. I think the most interesting thing with respect to platelets and in particular Plavix, which has been a cornerstone. Right. For us.
[00:18:52] Dr. St. Denis: Yes. Yeah.
[00:18:53] Dr. Gordan: Thanks to, you know, a lot of work that went into that by Dan Hogan and his group. But Josh Stern showed recently and presented at ACVIM that there's a number of cats that have a mutation that makes Plavix not work in them. And those helps us understand maybe so much why some of these cats just don't seem.
[00:19:12] Dr. St. Denis: Don't respond. Yeah.
[00:19:14] Dr. Gordan: Or you're like, oh, God, is it that bad? They have another one. So thank goodness for, you know, the factor 10A agents. Again, another unlabeled product for cats, but one that I'm more than happy to use under the right situation.
[00:19:27] Dr. St. Denis: Yeah. We've had some publications about the clopidogrel in response to, and looking at the different cats that may or may not respond. So I think we have Dr. Matt Corneilla at the University of Guelph who is doing some studies in that area as well. So looking at, even transporting samples to get them tested to see if the patient's going to respond before we start using them or while we're using them to make sure they're their value.
Because it sounds like it's a big enough percentage of cats that.
[00:19:54] Dr. Gordan: Yeah. Or just go for a factor. Go for a rivaroxaban. It's not. I don't, I don't know here. The price came down, so it's not cost prohibitive for us. Although it's still more money than Plavix. But for a little cat, not too bad. Like, big deal. But sorry, they're big dogs. Yeah.
[00:20:10] Dr. St. Denis: Not a concern for us. I guess when we're dealing with cats. You touched on the cases that you guys have in this review and I just wanted to say, in addition to the table, like, this is such a great thing to have there because it presents a number of scenarios. I think there's five or six of them of cats with CHF with heart disease that you've sort of worked through what's going on with them and, and what you may not. And you've presented them in such a way that sometimes we don't have data but an echocardiogram and what's going on and how you've sort of gone through that. And I found it interesting because a lot of them actually don't recommend pimobendan for. So that are. That was kind of interesting. Do you want to just touch on that a little bit? I mean, we've kind of been talking about it anyway, but
[00:20:52] Dr. Gordan: Yeah, we were trying to show, you know, because these are the sort of cats you encounter, you know, you might encounter a case where the cat comes in, you know, it has classic presentation for active heart failure. It's the first presentation of heart failure. You know, we've never seen this cat before. You know, radiographs may be minimally at least to confirm that they have an infiltrate pattern or a POCUS or something to say they have, you know, beelines or whatever. But you've come to that clinical conclusion that they have active heart failure and it's pleural effusion or, or maybe it is, but it's not a lot. You're after the infiltrates in the lungs that are contributing to the respiratory distress. You know, the question is, should you give it? I know there are some of my colleagues that might say every cat that needs Lasik should get pimobendan. And I'm not that person. And I don't think our group, as we came to discuss it, that that would represent the balance of people.
So to me, you would treat that cat like we normally do, which is parenteral ASICS and some support. And then you would decide, you know, because they're after Lasix, frankly, and, and when to add your sort of ATE prophylaxis and whatever that choice is. But to me, those might be the highest priority treatments. And a lot of cats will stabilize beautifully with a day in the hospital, right?
And I don't know, somewhere between four and eight mg/kg of Lasix over that 24 hour period. And, and then you're like, okay, if they do really well and they go home on just Lasik. Now two drugs to send a cat home, the first time on two meds is also a right. I mean, these are challenging things. I mean, every drug for a cat or every new pill, especially if the cats don't eat wet. I mean, Lasix you can hide, it's not, doesn't taste bad. Plavix tastes bad. So you have that problem, you know, on top of it. And I'm trying not to scare the owner off of chronic oral management of their cat. You have to speak up on polypharmacy.
So I don't want to get complicated fast. So we tried to show that that would be a cat that you should manage. And if he doesn't come back in, in heart failure for eight months, great, maybe a year. Right? Maybe he stayed very static for a long time. And he's a, he's a good responder, right. We always say initial response is a good prognostic indicator. And that's because it also tells you whether the owner can be compliant and how compliant is and other things. So my highest priority would be get rid of, you know, something for the fluid accumulation and an ATE prophylaxis protocol and then if that cat shows back up. We all believe by the way that the cats that come in the first time with a lot of pleural effusion might be a sicker cat. Cats love to do pleural effusion or even chylous effusion with heart failure. But they might be the sicker, the sicker version.
So let's say the cat represents in fulminant active heart failure inside of, you know, a month for the second time you're like, you know what, I can't mess around with this. Every time this cat comes back, the owner's stressed or he could end up in an emergency room, maybe you. And first of all you check compliance because it's possible the cat's not getting its pills. But if you're pretty sure there's pretty good compliance, they can do oral medications. Otherwise you can shift to an injectable Lasix and see how they stabilize on that home with preloaded syringes or teach them how. But otherwise that's when you might think about adding it. So we tried to give you the scenarios where treat a virgin failure like you would treat virgin failure but think about PIMO in your back pocket as a, as a backup plan.
Or you get the cat in heart failure the first time and you do end up with an echo inside of a few weeks to figure out what that phenotype looks like. Or yeah, and it turns out that he's a non specific cardiomyopathy and he has poor. Some reduction in LV systolic. I wouldn't wait to add. I would just add it in pretty quickly as long as the owner could do like three pills, three kinds of medicines. Now the solution is going to be really nice because you can do accurate dosing for cats.
And so you're not, you're not and you're not getting those chewable in this country. In the US it's chewable tablets that are quite large In Canada you guys have capsules which are equally obnoxious for cats.
Maybe, maybe not equally. But. And, but a solution that's not. And it's kind of a honey taste like it's a. It's. It's got a palatable flavor It's kind of like meloxicam. It's got that nice.
[00:25:03] Dr. St Denis: Yeah but cats seem to not mind for some reason.
[00:25:05] Dr. Gordan: For some reason. Right. So. So I think there's. There's a lot of considerations, Cat considerations.
But. But I. We tried to show people where we thought a good stepping off point was, but showed them that there's a lot of places where you don't need to consider it at the outset. Yeah.
[00:25:23] Dr. St. Denis: And I really appreciate that. And I certainly would say to our readers, like, when you're using this, I love these Clinical Spotlight articles as resources in my practice too, and this one's a gem from that perspective because we're confronted with these things and you know, in the middle of a day and we don't always know what to do. So it's really good to have access to just, even those case studies, Pimobendan aside, which is. I found them very helpful. So. And interesting.
[00:25:48] Dr. Gordan: I think sometimes if you can read something. And I thought like the clinical studies at the end that I really felt strongly about including in this paper were really just to.
To sort of show an application of what they read in a way that was probably digestible for a clinician.
[00:26:05] Dr. St. Denis: Yes. And very much so. In that good thinking process of, like you said, going through, is it a first timer? Have they relapsed? What do we know about their heart? Do we know anything that kind of situation? So very much.
[00:26:16] Dr. Gordan: What do we know about the owner relationship with the cat and the ability to medicate?
[00:26:21] Dr. St. Denis: Yeah. This is so much more than we.
I think, you know, I've been a vet for 25, 26 years now, and we've really gotten good at thinking about spectrum of care and that caregiver and caregiver burden as well as the patient.
[00:26:33] Dr. Gordan: Right.
[00:26:34] Dr. St. Denis: So I think that's. Those are really important considerations to take into as well.
So glad that you guys touched on that.
So I just wanted to say thank you. I think I could ask questions all day about not just pimple pandem, but cardiology as we sort of chatted before we started recording the podcast. So thank you to you and your authors for. For giving us this Clinical Spotlight article. I really appreciate it and it's going to be very well received.
[00:27:00] Conclusion: Thank you for listening to this episode of All Cats Considered. We hope you enjoyed this interview. For more information on the topics discussed in this episode, please head over to catvets.com podcasts and explore the links in the show notes. Don't forget to subscribe to this podcast on your platform of choice so you won't miss any episodes as we release them.
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