Is it Time to Add Colchicine to the CVD Cocktail?
I think most people would consider loco to to be a positive study again. Demonstrating the positive effects. That culture scene can have on cardiovascular outcomes in looking at the conduct of the study. What do you consider to be the strengths and potential weaknesses. What concerns does it raise and does this study established culture seen as a standard of care that should be offered to most patients with coronary artery disease or just to some patients or just a limited view. Yes i'm going to go ahead and quickly Discussed the strengths. This was a randomized placebo. Controlled double blind trial. They had a large sample size around fifty. Five hundred patients were randomized. These patients were on solid background. Therapy as i discuss previously. And i think this answers are very important. Clinical question about further risk reduction in patients with cad. Yes so. I completely agree. I mean this is a a well done study with no real fatal flaws. But certainly. There's some things discuss here so i or a couple of things regarding the design of the trial. That really. Back to the generalize ability the findings so i the trial like taylor said was done primarily male patient population specifically in western australia and netherlands. So as unfortunately we see often cardiovascular literature women were underrepresented here in the extrapolation other ethnic groups may be challenged. But the. I don't see this at this. Point is a fatal flaw and i don't have any real biological reason to think that the results wouldn't extrapolate other groups next specifically the culture seem does that was used was point five milligrams which is different than the zero point six milligrams at least we have here in the us. So for some of this could be an issue in what's unknown at this point is if this twenty percent difference in concentration could ultimately impact you the outcomes whether the efficacy or safety however again my gut says it's it's probably k. We've extrapolated from some of the pericarditis data and used are kinda us doses with benefit. So with those said. I think the biggest issue kind of discuss regarding this trial is the priroda musician running phase so against dealer alluded to patients after they were enrolled went into a one month. Essentially tolerability running phase in which fifteen percent of patients actually dropped out during this phase before random ization patients dropped out about sixty percent or overall about nine percent of the overall enrollment phase was lost to perceived side effects for which about half were gi related. As you'd expect with culture scene for me this dropout rate largely for eighty are reasons. Make really me question. The finding of equal discontinuation rates between the trial arms in might skew what we might actually see in clinical practice so i don't think losing sight of shore educating patients about possible side effects from a statistical standpoint you can have the consideration that dropping patients pre random ization due to tolerability concerns. Kind of enriches your potential drug effect. You don't have those patients in the intention to treat arm who aren't exposed to the drug so possibly is looking drug effect versus placebo. Based on what you'd expect in practice you may potentially not see the same overwhelming benefit but the benefit was very strong. And i don't think adding those patients back in would necessarily change the overall Interpretation trial or the application. So really from running phases very much a A safety issue versus inefficacy issue. So alternate of. Bring that back to get back to coach. Seems place in therapy ultimate At this point. I really think lonzo to help to continue to confirm the potential benefit of colchicine in cad management. When we look at this along with other trials whether it be the local one and then probably most importantly combine this along with the whole cod study. We see it but largely consistent benefit with culture seeing reducing cardiovascular events out for those familiar with the study may also seen that at the same time the lotto co two was presented also. A study called cops was presented and this is specific australian study that looked at culture again in an acs population now. This was a negative study. But the real caveat with that is the trial was actually powered for very large difference in events so it really was underpowered to potentially detect. What we what was suggested as possibly clinically relevant differences power. Find about a fifty percent difference in. It looked like there might have been about thirty percent difference. Which is what's consistent with other studies. So kinda really negates. The ability for that trial to kind of pooh-poohed on potential benefits here and i really think ultimately what we have to ask ourselves is is this nonfatal event risk reduction enough to make a therapy part of standard therapy in will i'd say softer endpoint is at play here. It's probably at least reasonable that it's something that we can't just throw out