GameChangers: Colchicine Use Post-MI

In this week's GameChangers we explore the emerging role of colchicine in the secondary prevention of cardiovascular disease. Drs. Wall and Boyd discuss colchicine's anti-inflammatory benefits, the challenges posed by side effects and drug interactions, and the latest research shaping its future in clinical practice. 

The GameChanger
Colchicine shows potential for secondary prevention in cardiovascular disease due to its anti-inflammatory properties, but its clinical use is limited by gastrointestinal side effects and drug interactions. 

 
Host
Geoff Wall, PharmD, BCPS, FCCP, BCGP
Professor of Pharmacy Practice, Drake University
Internal Medicine/Critical Care, UnityPoint Health

Mathew Boyd, PharmD
Clinical Pharmacist, Unity Point

Reference
Meta-Analysis
Clear Synergy Study

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CPE Information
 
Learning Objectives
Upon successful completion of this knowledge-based activity, participants should be able to:
1. Identify the potential benefits of colchicine in secondary prevention of cardiovascular disease based on its anti-inflammatory properties.
2. Discuss the limitations of colchicine use in clinical practice, including gastrointestinal side effects and drug interactions.

0.05 CEU/0.5 Hr
UAN: 0107-0000-24-190-H01-P
Initial release date: 06/17/2024
Expiration date: 06/17/2025
Additional CPE details can be found here.

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Transcript

Speaker 1: 0:08

Hey CE Plan members From CE Impact. This is Game Changers. I'm Jen Moulton and today's clinical conversation is with Jeff Wall and Matt Boyd, who are colleagues at UnityPoint Medical Center in Des Moines, iowa. Welcome to you both.

Speaker 2: 0:22

Well, thanks, Jen. We appreciate having us with us.

Speaker 1: 0:26

Des Moines, iowa. Welcome to you both. Well, thanks, jen. We appreciate having us with us. Yeah, well, I'm excited about today's topic. One might look at the drug we're talking about today and wonder why it's a game changer when it's one of the oldest drugs in the pharmacopoeia. But what we're really talking about is a different use for an old drug, and that drug is colchicine. So we are talking about it not for its traditional use in managing gout, but in utilizing its anti-inflammatory properties for the prevention and treatment of acute coronary syndrome. So there have been a lot of studies or several studies, I guess, lately in this area, and I know you're all going to review those today. So let's get into it.

Speaker 2: 1:00

All right. Well, again I want to take a moment and thank my colleague, matt Boyd, who's here. He's our cardiology clinical pharmacist here at Methodist and is well-trained in this, and I appreciate it, as always, when he gets to guest star on here and gives us his expertise and his practice insights. So again, matt, welcome, and we appreciate you being here. So you know, yeah, as Jen points out, you know this is this isn't like something like brand spanking new hot off the press. The reason for it was largely there was a meta-analysis that just came out last month that took a look at this issue and I thought you know we really have never done this, and it is kind of an interesting way to treat coronary disease and I mean, there's been a couple of studies and everything.

Speaker 2: 1:47

But you know, I think Matt and I both kind of agreed that we really haven't seen a huge uptick of its use. You know, it's like you know, often with with with medications, you know, post MI or secondary prevention of coronary disease, cardiologists, I think, matt, I don't know, see what you think, but I've always. I think most cardiologists are what we'd call early adopters, right, I think, yeah, I don't. They don't wait for a year after a drug to come out to go. Okay, well, I guess we'll give it a shot now. I mean, you know, I think cardiologists are among the subspecialists who tend to be pretty up on the literature and I think they're they're the you know what they would consider early adopters, and that's not what I've seen here and I and I think, matt, you were saying the same thing here in Des Moines we have not seen a huge uptake in colchicine in this. So again, we thought it was kind of worth, worth, worth going through. So you may say to yourself, okay, well, why would colchicine work, you know, and and it all comes down to inflammation and, and as we know from gout, colchicine has been used for you know what 5,000 years or some something like that. I think it came out the year before I became a pharmacist. Actually it came out a long time ago for for, for the treatment of gout. It's, it's, it's been, it's one of the oldest drugs in the pharmacopoeia. It was one of the big treatments that even Hippocrates had written about. So I mean, we have a long, long, long history of its use, and again, primarily in gout.

Speaker 2: 3:14

But we know that its anti-inflammatory properties may expand out beyond rheumatologic disorders. For example, it's FDA approved for familial Mediterranean fever, which I don't see a lot in my world, but but I mean, is is definitely an inflammatory condition that actually works really well for. So you know, and and so then what that brings us back to is is the notion that cardiovascular disease is, or atherosclerotic cardiovascular disease is, at least as much a disease of inflammation as it is a platelet dysfunction or, you know, dyslipidemia or anything along those lines. And in fact you know, again, this is old data, this isn't like brand new, spanking data, but you know, data clean back to the Jupiter study, which came out in the early 2000s showed that statins had, you know, their ability to improve outcomes had as much to do with their anti-inflammatory properties as they did their antilipid properties. And in the Jupiter study it's actually what they did was they took a look at CRPs in these patients and if they were elevated they went up on the dose of the statin. And then they did a postdoc analysis also, where they took a look at people whose CRPs went down after they started on a statin and their outcomes were better than people who's who's were on statins and their CRP didn't go down, even if their lipids went down. So so again, the notion that inflammation plays a key role in in, uh, uh, an acute coronary syndrome is is again not new. I mean, we've known her for a long time, but I think we've kind of hit a uh, um, a plateau as far as what statins can do. I think you know we've reached a point now where you know the stats have been literally studied into the ground. We know exactly what they do, how they work. You know, I know, you know we're trying to add on secondary drugs like the PCSK9 drugs and some of these other newer benpidoic acid and all that other stuff, and I mean that's great, except that you know these drugs are horrendously expensive. Their data for secondary prevention isn't nearly as robust as with statins. So I mean, you know, I'm not sure those are going to kind of take over. But the beauty of colchicine is it's relatively cheap. It's not as cheap as it used to be, as any rheumatologist will tell you, but it's cheaper than it used to be. And so if it does have a benefit, I mean it would be a cheap added benefit.

Speaker 2: 5:29

The reason colchicine is particularly targeted is that neutrophils play a big role in the infiltration of the coronary artery. The change that happens in coronary arteries when a certain amount of lipid deposit is on the interior of the artery, you know that's. You know interleukin one, some of the other interleukins you know, trigger this pro-inflammatory response. Neutrophils get involved and of course, as I always like to teach my students, I don't matter if you want to do this, but you know I always say well, you know they activate the macrophages which essentially Pac-Man their way through the, through the side of the of the artery wall, you know sort of thing, and that's kind of what leads to this big cascade. So, since colchicine has effects primarily in the neutrophilic pathway of inflammation.

Speaker 2: 6:13

Okay, there's, there's definitely some biologic plausibility that would work. So what evidence you know has come out that has looked at this? And the first study that that looked at this was a randomized study called the LIDOCO study and this was for secondary prevention of cardiovascular disease. It was an RCT. It only had 532 patients, which in the world of cardiology is not even a rounding error, unfortunately.

Speaker 2: 6:37

But I mean, yeah, I think, for proof of concept, I think it was, I think it was reasonable, right, and so, and what they did in this study is they randomized patients to colchicine 0.5 a day, uh, or placebo, and they looked at their ad at the composite end point like all these cardiology studies now are composite end points of of some MACE category, including acute coronary syndrome, out of hospital cardiac arrest, non-cardioembolic ischemic stroke, and they found that colchicine in fact did do that, that, that in this study, um, uh, there was a statistically significant decrease in MACE in the patients who received colchicine compared to placebo, but it was driven, uh, and it was driven mostly by a reduction in acute coronary syndrome and the in the original study they calculated only a number needed to treat of 11 patients, which would be incredibly cost-effective and powerful findings.

Speaker 2: 7:26

A second study, the LIDOCO2 study, was a much bigger study, 10 times bigger, as a matter of fact that looked at pretty much the same things. I think LIDOCO1, they tried to like you know, is this even going to be a thing? And then it was. And so then they tried to validate that with LIDOCO2 and similar outcomes. They found a 31% relative risk reduction in cardiovascular death, spontaneous MI, ischemic stroke or ischemia-driven coronary revascularization. Now if you're saying to yourself, one of those things is not like the other, yeah, you're right.

Speaker 2: 7:58

I think we would all agree that revascularization is always considered kind of a soft endpoint in these MACE outcomes. Revascularization is always considered kind of a soft end point in these MACE outcomes and unfortunately that's where this was. Most of the benefit was driven by that outcome. However, in a post hoc analysis, when they even took that out and they just looked at the other three, they still found a statistically significant decrease 4.2% of the rest of the MACE outcomes in the colchicine group, compared to 5.7 in the placebo group, which was associated with about a 28% relative risk reduction.

Speaker 2: 8:31

So, I mean again, considering how relatively cheap colchicine is, maybe not such a bad thing. So, for secondary prevention, it certainly seemed like there was at least some studies that suggest that, yeah, there is this benefit. Okay, well, that's in patients who had long had their event, right. What about patients who are having an acute MI? Well, that is studied and is being studied, but the first study that looked at this was the COPS study. This was a study that again randomized patients who had acute coronary syndrome and received colchicine 0.5 milligrams twice a day for a month, followed by 0.5 milligrams daily for 11 months. I guess they can start and stop at the same time they start their DAPT. In this study it was again not a big study by cardiology standards on about 800 patients, they found, unfortunately, that randomization to colchicine did not reduce the primary MACE outcome of death from any cause acute coronary syndrome, ischemia-driven or urgent revascularization or non-cardiobolic stroke at one year. Now, again, this study was a small study. Numerically the numbers were better with colchicine versus placebo, but they just didn't have the power to reach statistical significance and in fact there was, I think, somewhat of a concerning signal for increased total mortality in patients who were treated with colchicine, and so they did a post hoc and now, like the numbers are a little bit higher with total mortality, they did a post hoc analysis of a composite endpoint just using cardiovascular rather than all-cause mortality, and that did find a statistically significant decrease. So a little bit of a hiccup there in using it for acute coronary syndromes. But I think clear enough that another study which was done, which is the Colcott study. This study was a randomized or a double-blind, placebo-controlled study of about again 4,700 patients and did pretty much the exact same thing and the patients were supposed to receive colchicine in the hospital or if they've had an MI in the last 30 days. In Colcott they found patients who were randomized to colchicine 0.5 a day did have a 23% relative risk reduction in cardiovascular death, resuscitated cardiac arrest, as opposed to resuscitated cardiac arrest. Sorry, I got a phone call at the exact same time, so starting again in three, two, one. So in the COPS study what they found was that those randomized to colchicine 0.5 milligrams a day had a 23% risk reduction in cardiovascular death, resuscitated cardiac arrest, mi, stroke or urgent hospitalization for angina requiring PCI over a meeting of 22 months. This effect was largely driven by a reduction in stroke, which is kind of interesting because that's not usually what you would expect to see. A sub-analysis of the Colcott study found that early initiation of low-dose colchicine within the first three days after an MI was associated with a 48% relative risk reduction in the primary endpoint, driven by a reduction across the board in acute MI, stroke and urgent hospitalization for angina. So it looks like the data for secondary prevention is actually okay. The data for acute coronary syndromes is a little more plus minus, probably more plus than minus.

Speaker 2: 11:52

And then we get into the hot topic that is being studied right now, which of course would make the most sense, which is colchicine during a percutaneous coronary intervention. We only have really one study, though there's another big, big study that we're looking at that's being ongoing right now, but the colchicine PCI study sought to determine the effects of paraprocedural colchicine and looking at outcomes. There was a randomized, double-blind, placebo-controlled, single-center study of 714 patients that was referred for PCI in the setting of acute coronary syndrome or stable cardiovascular disease-loaded patients with colchicine 1.2 milligrams one to two hours before PCI, followed by colchicine 0.6 immediately post-procedure. So again, just you know the the right around the procedure. Uh, the PCI related myocardial infarction or 30 day major adverse cardiac events which defined as all cause death. Non-fatal MI target vessel revascularization was not reduced with this load of colchicine, and an extended follow-up looking at cardiovascular events over a meeting of three years also did not demonstrate a benefit. So at least the studies that has been published currently with this kind of gout-like load of colchicine around PCI did not find a benefit, and so that's kind of where that went.

Speaker 2: 13:10

However, a new study or an ongoing study is looking at not only the load of colchicine around PCI but then continued use after PCI to see if there's a benefit in that, and I don't know when that study is is, is, is due to be, is due to be published, so so that's kind of a summary of literature to date, you know. So you know, matt, you know, I know you've read all these studies. I'm sure you know a hundred times better than I do what's your take on colchicine. You know what's your take on the studies and we, you know where do we? You know, where would you see us using this and where would you see yourself recommending it?

Speaker 4: 13:46

Yeah, it's kind of hard. It's like, especially in cardiology, most of these patients will come in, never you know. They either haven't seen a physician forever, which doesn't help, and so that means that they're coming in and we have a whole new sort of comorbidities that they're coming in with, going home on a bunch of new meds and the meds that we have now, being aspirin, you know, our P2Y12 inhibitors, um which most commonly I would say, is probably Plavix and Berlinta Um.

Speaker 4: 14:13

And then we have our statins, which are pretty well tolerated for patients, and then they normally go home on a beta blocker and a tiny amount of ACE. So you go from having zero meds already to now you're going home on at least five or six meds just solely because you had chest pain and you were out riding your bike.

Speaker 4: 14:31

And you subsequently have now a new stint in your heart, and so now you'll be on these meds probably lifelong, and all of these studies they do have benefit in that, and I'm not and I'm not denying that a bunch of them do have pretty good literature behind them, and I feel like if it was any other medication, this probably would have probably taken wind a lot longer ago. Or you swap out the word coltacine and put the word atorvastatin in there, like that would have already people would have been on board already. I think the big thing for us, though, and just cardio and cardiology in general, is colchicine is not super well tolerated, as you can see in most of these studies. A lot of them either patients stopped it because of GI side effects or, um, just like other neutropenias from being on this medication, but I would say that the most common one is going to be our GI side effects for colchicine.

Speaker 4: 15:23

I feel like in most of these studies it was at least up to 20 to 30%, which is pretty remarkable considering most of the side effects that we have for medications even like our common ones. Like a cough with an ACE inhibitor, those are like less than 5%, and so this is a pretty robust adverse effect from being on this medication and then I feel like it's a med that also has, like very we talked about it earlier very sneaky drug interactions, right, not drug interactions, you know that we commonly think about in school. But colchicine is going to interact with, like our carbadolol, which is one of our three beta blockers that we use religiously in our cardiology population Right, almost to the point where, if you're going to be on 0.6 of colchicinea day, I think the recommended dose reduction is like 0.3 on Monday and Thursday which, like who has time to remember to take a colchicine half a tablet on Monday and Thursday every week.

Speaker 4: 16:14

Definitely not me and I can barely remember to take the meds that I have to take now. I agree, and so I would say that is part of the reason.

Speaker 4: 16:23

One not well tolerated to a lot of drug interactions, so I'm sure providers got into the habit of either being called from their lovely pharmacist about drug interactions and not wanting to have that be a headache for them, them, but also just like another thing that they had to remember too on top of everything, on top of the ACE, on top of the beta blocker, on top of the P2I12, on top of the aspirin, on top of the statin you know you're just adding to a laundry list of medications and I think, the other meds that we have for these post MI patients, or at least like stable coronary artery disease patients. I feel like we have very robust data for all of those medications and all of them have, like, very strong literature to support, like cardiovascular mortality, maybe minus the aspirin that you know was studied from the 1980s, um, but I would say most of them have pretty robust data behind them. And so I think, in the term of cardiology, I think we stick with things that we know, which is, you know, it's very hard to reinvent the wheel, especially in MI care, but I feel like a lot of cardiologists are very quick to jump on what's new, what's you know upcoming in the literature, and this just has never taken a strong wind at any institution that I've ever worked at. I would say the most common cause or use of colchicine in our cardiovascular population is going to be our pericarditis patients, and even then, you know, we have them on it for 30 days, maybe 60. And then after that it's done, and sometimes even that is a struggle, or struggle to get through insurance, just because you know insurance thinks it's always going to be used like the 0.6 every 30 days for gout flare. So I think sometimes insurance is a little bit of an issue too.

Speaker 4: 18:05

But I would say from the standpoint of just like post MI care, I think this is just an additional med that, while it does have pretty robust data on it right now, isn't super well tolerated, doesn't have as robust of data as you know, our beta blockers, our ACE inhibitors, and so I think it just kind of falls to the wayside because it also hasn't really been studied in any of our heart failure population at all either. And I feel, like post MI care, we almost always have some sort of stress induced cardiomyopathy from what's going on, um, and a lot of these studies excluded patients that had any heart failure symptoms or they excluded patients that had any reduced ejection fraction at all, um, and so I think that's kind of it kind of almost falls into the class of like NSAIDs and a lot of cardiologists minds um which, for those of you who don't know, or don't know already, that NSAIDs are a huge no-no in cardiology Um unless it is again pericarditis, which I feel like just breaks all the rules in the world of cardiology.

Speaker 4: 19:02

But I would say it's just something that's never really caught wind and I don't necessarily know if it's ever going to, unless there's like this huge trial on top of all of this already available literature that really shows just like huge, you know, reduction in cardiovascular mortality or at least readmissions. You know reduction in cardiovascular mortality or at least readmissions, you know, because that's the constant battle that cardiology fights all the time is the readmit within 30 days or 60 days. So I don't really feel like it's ever going to catch wind. But you know, who knows, maybe somewhere down the line if they create some colchicine medication like, almost like, dreneterone, for ADL that like is more tolerated and it doesn't have as many side effects.

Speaker 4: 19:40

Maybe one day, one day we'll catch on.

Speaker 2: 19:43

So I I appreciate you bringing the interactions to light because, as you point out, I you know, everybody is well aware of a lot of the cyclone.

Speaker 2: 19:52

try to pump you for 50 stuff and I mean you know so I mean, but but you know this, this is, this is not only a metabolism thing, but just additive side effects you know, colchicine in and of itself causes myopathy, it causes myalgias, it causes muscle pain, it can cause rhabdo, and so you know, you can bet your bottom dollar that somebody who's on a high dose statin, who probably already is kind of irked about taking the statin and maybe has a bit of muscle pain, then you add on this colchicine and then they're really going to be mad and oh man, I can't tolerate any of this stuff and I'm going to stop all this stuff.

Speaker 2: 20:23

So, yeah, I, you know I, and you mentioned the carbadolol. You know, again, I think, for the pharmacist listening, were this to become kind of you know more of the standard of care, I think we would have to be very careful about drug interaction monitoring, because I don't think a lot of this stuff is going to show up on a POC reties when physicians are prescribing it. So I think that's it. So I'm glad you brought that up. So I've read some stuff that says okay, so if colchicine is and I like the way that you phrase that we've gotten a lot of these patients from zero to four, zero to five, zero to six medications, and now we're going to add another medication that you know may not be well tolerated.

Speaker 2: 21:06

The benefit, frankly, is not as robust as statins, p2i drugs. So you know, and you're adding the Pilbert. So I think you know.

Speaker 2: 21:17

Maybe some cardiologists are like, yeah, if a study came out that showed that it, you know, halved cardiovascular mortality, okay well yeah, that's, that's worth an extra pill a day, but, but considering that a lot of this stuff was driven by, as they point out, you know, we talked about in the studies pretty soft outcomes, right, you know, and which is always and again, you know Matt knows this cause, he reads these kinds of studies all the time. But one of the issues that you always get with major adverse cardiac event, uh, as outcomes and studies, is you have to kind of make sure that the drug, the study, is not only power to look at a different set, the at the out, the all overall outcome, but a lot of these studies now are designing their trials so that you can look at each secondary outcome independently, because you have to, you know, because you know it's like, well, you know, you know, well, you know we, we counted a major adverse cardiac event, as you know, death from cardiovascular disease, mi, stroke, need for revascularization or some chest pain, when I went to the bathroom yesterday, and you know it's like okay, again, one of these things is not like the others, you know, and and so, yeah, that's that. I think that that's an important piece. So so I guess then, you know, given all that, given the, the, the poor tolerability. Given the you know all that.

Speaker 2: 22:27

Would there be a patient who you would advocate on rounds for? And I've read a couple of little verbs and you probably did too where people are saying well, okay, well, if you're on the fence about colchicine, just like we did back in the day with statins, check a high sensitivity CRP on the stat. If it's elevated you can say, okay, there's definitely inflammation there, let's try colchicine. So you know, would there be a patient you would advocate that?

Speaker 4: 22:51

Yeah, I would say for their patients that you know we have multiple patients and most people, especially in the Midwest, don't just come in for one stint. Most people have multiple stands throughout the course of their life. Um, and I would say a lot of it for the patient population that I would advocate for is the ones who come in all the time and there's really no new targets to hit for the cardiologist or the interventionalist. You know, nothing new to stint, nothing new to kind of like angioplasty open, everything's kind of just the best it's going to get, whether they have already had a cabbage and all of that. I would say, the patients that persistently come in for, almost like that, chest pain, you know, who are on that IMDR medication, which is, you know, another one that is an added side effect that people will have high, like headaches and stuff for, but, um, I would say, the patients who persistently come in chest pain concerning for, you know, having another end, stemi, which I feel like that is just something that's, you know, innate in these people.

Speaker 2: 23:50

Once they've had one.

Speaker 4: 23:51

STEMI. They kind of always think any chest pain is going to be a new STEMI. I would say, for that patient population, those who you know no new targets, have persistent chest pain, have like pretty substantial coronary artery disease, those are the people that I might try to like target, or at least attempt to see if it is beneficial for them. Sure, just because it is, you know, an anti-inflammatory, it's not going to have the same negative side effects that, like an n-set would right, um, and you're going to have some sort of you know reduce an inflammation, whether that be in their coronary arteries, um, just like around their pericardial fluid in general, you know cause we use it for pericarditis.

Speaker 4: 24:31

I would say that's the patient population that I most common would see it in or would use it in the most often, um only because at that point we really don't have anything else to offer these patients.

Speaker 4: 24:43

You know like you can start ranolazine in people, but that works about as well as just smelling inder as you walk by, you know so I can't necessarily say that ranolazine is going to be like the cure all year for these people, and maybe this medication, since it is an anti-inflammatory, can have some better long-term effects for them. I just don't necessarily know the longevity of when you start this medication on somebody, how long they really can tolerate it. Because I don't really feel like this is a med, that people are going to be able to, you know, start at age of 50 and then be able to tolerate until like their nineties.

Speaker 2: 25:16

I just don't see it that. Yeah, I agree with that. That that's interesting. And do you think CRPs would be a go no go for you at this point, or do you think so? I?

Speaker 4: 25:23

don't necessarily think we check CRPs very often in cardiology I feel like that's a lot of the a lot of like GI or maybe crit care that check CRPs more often. But I would not necessarily think that would be a bad test to check if someone is persistently coming in, you know, for new cardiac symptoms and you can't really pinpoint what's going on, especially if you know they go in, get a cath and there's nothing really new to do. I think getting a CRP would be appropriate and kind of help to guide, like whether or not there's a robust amount of inflammation and help her to go?

Speaker 2: 25:54

Yeah, exactly, and if?

Speaker 4: 25:56

it's low, then you're like, ok, perfect, so it's probably not something that was going to be beneficial, but if your CRP is high it can't necessarily hurt to at least give it a trial, and if it comes down and their symptoms go away, then I think that would be appropriate.

Speaker 2: 26:08

I like that, I think, I think that's a pragmatic approach, that that seems to work well and again, it's it's worth noting that they did they, they didn't really do that in most of these studies, and so you know, I'd be. You know, I've heard some experts kind of say, hey, that that you know, the idea of getting a high sensitivity CRP might help you, help you with the go no go. But I like that, I like you know, again, always looking at the patient. You know you've got a 45 year old dude, you know, who's relatively young, but I don't, you know, has a terrible familial history or something and it's had, you know, a couple of heart attacks and and he's, he's got stents in and you've already got him on a full court press. I mean you've, you know, you've literally got him on everything, including a high intensity statin, and he's still coming in with chest pain. Yeah, I mean I, that would be the kind of patient, yeah, I agree with you. You know, check a CRP, but it's high, it's like let's give it a shot. You know, are you tolerating this? Are you pooping your brains out, are you? You know, are you puking all the time? Okay, well, no, you know, and your white cow seems to be okie doke and you're not complaining to muscle pain issues. Let's, let's give it a shot and see what happens. I like that a lot. So we're going to wrap up really quick.

Speaker 2: 27:16

You know the impetus for, even though the use of colchicine is not new, lidoco came out a couple of years ago. There was a brand new meta-analysis that I pulled, I think about last month, and I think that's what kind of triggered me to maybe actually take a look at this. And so this was a study. It was yeah, I think it was pretty well done meta-analyses. They basically only looked at RCT, so basically looked at all the studies we just talked about, right, colcott, lidoco, all the COPS, all these other studies, and they wanted to look at the individual outcomes associated with these studies. So they looked at, instead of bringing all the different MESAs together, I think they wanted to use meta-analytic techniques that then have the power to break things up, to take a look at these individual outcomes as opposed to all of them wrapped, these individual uh uh outcomes as opposed to all of them wrapped together, which again, they were kind of all over the board.

Speaker 2: 28:09

And so when you take a look at that, you know, I uh, you know, on the whole, most of the outcomes were beneficial. But when you take a look particularly um at at uh uh patients who had a stable cardiovascular disease, uh, there was a. Uh a was a slight benefit. It wasn't gigantic but they found that on the whole it was somewhere around a 35% relative risk reduction in symptoms and all these MACE outcomes that people had stable coronary disease symptoms and and all these MACE outcomes that people had stable coronary disease and in acute coronary syndromes, they found basically uh a a benefit to with uh, a about again, about a 33% relative risk reduction in in in all all coming in, all these different outcomes.

Speaker 2: 28:56

but then you break them down and, for example, they looked at at cardiovascular death. Cardiovascular death that in fact, uh, when they looked at all the different studies together, had actually a 30% relative risk reduction. So that's interesting. Myocardial infarction had a 25% relative risk reduction, um, and then a stroke. And again they noted this in the in in in the uh Colcott study uh actually had a um, um, actually had, I'm sorry, a almost 50% relative risk reduction. So again, it's a meta-analysis. So you know, we could do an entire podcast on how much weight you get meta-analyses, but I think you know what. I think that the purpose of this meta-analysis that was to basically try and show that, even though these studies were a little bit disparate in their outcomes, when you kind of bring all the people together there does seem to be a consistent outcome and some of the outcome seems to be pretty good.

Speaker 2: 29:48

It would be very interesting to note if you know, if you have a patient who's a known vascular path, do you end up putting patients on colchicine if they've had a stroke? Right, you know we don't. I mean, compared to QMI, we have many fewer interventions to offer these patients, and so, if you know, coltacine were to be an agent that would help with acute ischemic stroke, that would be a big game changer. I think that would happen. So so any last thoughts, matt, about what you'd like to.

Speaker 2: 30:17

I mean, like I said, apparently the name of this study and of course, like an idiot, I didn't write it down so I've got to look it up really quick but apparently the name of the study, if I can bring it up, is the Clear Synergy Study seems to be is the study that the cardiovascular community is eagerly awaiting, according to this review paper right now. So 7,000 patients. And again, this is the study where they're actually going to look at loading patients with colchicine around a PCI and then continuing it for a year after. So I mean, really that's going to mirror what the hell we do in real life anyway. So I think I kind of like that. So wrap up thoughts.

Speaker 4: 30:56

No, just if you see colchicine used in these indications, just make sure you check those drug interactions, make sure you can tolerate the uh tolerate, the patient can tolerate the medication, and just if they, if they can tolerate it. And who knows, maybe this will be one of those things that can be beneficial in the long run, but right now I just don't see it's. You know, pinpoint Right.

Speaker 2: 31:15

Not ready for prime time, not ready for prime time. All right. So, jen, that's kind of where we're at.

Speaker 1: 31:21

Awesome. Thank you so much. I always it's like having a virtual thought partner. You know to sort of sort through some of these studies, so I love that. Thank you for the conversation. That was really great. That is it for this week. If you're a CE plan member, be sure to claim your CE credit for this episode by logging in at CEimpactcom and, as always, have a great week and keep learning. We'll talk to y'all next week.

Speaker 3: 31:52

Thanks for listening in. Claim your CE credit by clicking on the link in the show notes and check out CEimpact's other education at CEimpactcom, where we curate the most important information in pharmacy and medicine to deliver straight to you. Join today to connect your learning to practice.