Kari Tikkinen: I'm pleasured and honored to be here.
Zachary Klaassen: Let's just back up a little bit. Just so patients know what we're talking about, tranexamic acid, when is it used? Why is it used? Why is it important for people doing urologic surgery?
Kari Tikkinen: Very good question. Tranexamic acid, in short, TXA, it's an antifibrinolytic drug. Very old drug. Very much used in orthopedic surgery, cardiac surgery. It's normal, routinely use there to decrease bleeding. In urology, most urologists don't use it routinely. Surveys say that it's infrequently used. Urologists are worried about clot retention. There's no evidence, but they are worried about it. They're worried about that this evidence from other areas doesn't apply to us, and they're very worried about that it would increase thrombosis. Because of these things, there are several RCTs in urology. Almost all of them are very small. Most of them are not blinded, but typically, they have suggested actually quite the same what we found. But there are two, I would think, good trials or bigger and more trustworthy trials before posterior urology. 15, 16 years ago, there was a trial conducted in Milan, published in the BMJ from San Rafael, open radical prostatectomy, 100 patient versus 100 patients. They showed actually a very similar effect in decrease of transfusions as we did.
Then there was another trial published a little bit more than a year ago, another good trial called TACT led by Rodney Breau in Ottawa, they did not find in radical cystectomy. But these both were smaller, so we are by far the largest. They had two procedures. We had a variety of urologic surgery. We had both those. The most common we had is robotics. Robotic prostatectomy, then we had radical laparoscopic nephrectomy, cystectomy. Anyways, the background was that it's used outside urology, rarely in urology, some worries, and so because of all these things, not much used, and no guidelines. AUA has no recommendation for or against. EAU has no recommendation for or against. And it's cheap. It's very easy to give. So, I think it's a relevant study and analysis for us.
Zachary Klaassen: Yeah, great background. Just lay out the POISE-3 trial for us. It's not just urology, it's other procedures as well. But layout the trial design also lay out the primary safety and efficacy outcome as well.
Kari Tikkinen: The POISE-3 is a very big trial. About 10,000 patients. Everybody gets either TXA or placebo just before surgery and after surgery. The two times 1 gram bolus before and after. Of these 10,00, 1,000 are urologic surgeries. We went back to this, everyone, and looked what exactly procedure they were. We double checked everything so that they are really urology, they are nothing else, and what exactly procedure it was, so we have information from them. Of course, we are underpowered for any procedure subgroup analysis because the biggest was robotic prostatectomy is like 160, 70 patients. TURP is the same amount and then it goes smaller like nephrectomies. But we had all kinds of urologic surgery, open, laparoscopic, robotic, endourologic, transurethral, and PCNL, percutaneous. Also, it was done one-third here, with here meaning North America, Canada, US, one-third Europe, one-third Asia and Pacific. So that kind of trial, this 1,100. And then the outcome was at 30 days
Zachary Klaassen: Okay.
Kari Tikkinen: And there was two outcomes. I mean, there are several outcomes, but two primary outcomes, primary efficacy, which is for bleeding. We tried to decrease bleeding. And then primary safety, which is thrombosis. We try not to, we looked at if we increase thrombosis. What we found in the primary bleeding outcome, we found it about 30% decrease. Statistically not significant. But what was statistical was the component of major bleeding. We had two major bleeding outcomes. In both ways it was. Major bleeding meaning not life-threatening bleeding, but needing transfusion or reoperations, ambulations or go back to the OR. So it's really patient important, but it's not the very, very worst ones, the life-threatening, critical organ bleedings. We did not find difference there. We found the difference in the major bleeding, which sort of makes sense. If you break a big [inaudible 00:05:37] or something in somewhere, okay, we don't do that in urology.
But anyways, if you really leave something life-threatening open, that TXA doesn't help. So it makes sense in that sense. The other side of the coin was thrombosis and it's very... Okay, little bit back to this major bleeding where we found this 37% decrease, it's largely driven by transfusions. So it's mainly transfusions what we can decrease with tranexamic acid. We can discuss more about them, but that's certain other implications then. But the thrombosis thing was again, composite and which was largely driven by so called MINS, myocardial injury after non-cardiac surgery, which means troponin elevation. We didn't find statistically difference, but almost all of those events were dose. We had only five patient important events in both arms.
Zachary Klaassen: Wow.
Kari Tikkinen: So three VTs in both arms symptomatic and two strokes in both arms. So obviously having 10 events total patient important were underpowered to say anything, but at least there was no difference. There is a lot of research on this thrombosis in randomized trials outside urology. In anesthesiology, there was a systematic meta analysis which looked in 40,000 patients, mostly not urologic. They looked this issue and they did not find increased thrombosis. So I'm not saying it cannot cause it, but at least the increase is not large. And actually what was different in POISE-3 compared to earlier trials, we only included the patient was at increased risk of thrombosis and increased risk of bleeding both. So typically trials excluded, they were worried about this, but we actually wanted them because we knew that people are otherwise saying that you excluded them now. So we actually have very relevant patient population.
Zachary Klaassen: It's a fantastic overview of the results. I think the big question is, how do we take this back to our clinic, back to our operating rooms now? So what would you recommend for, let's say, an open nephrectomy or a cystectomy? I know you don't have the data for subgroups, but what would your general recommendation be to our listeners?
Kari Tikkinen: Yeah, this is a key question. Thank you. So first of all, not in our trial, there was not a single seizure, but we know from at least earlier evidence suggests that tranexamic acid can increase risk of seizures. So that's probably the only patient population where I personally use tranexamic as in routinely after seeing the results, but I always ask, "Do you have seizures, epilepsy?" And then I'm not yet at least using for those patients at all. But other than that, the question is about the baseline risk. So all those where you think there's increased risk of bleeding, then you should either recommend or at least consider. And what is then increased bleeding? I mean, radical cystectomy, of course, transfusion rates are high. Then TRP is a good example of that it's a little bit different risk of bleeding. You probably don't die for the bleeding, but you have a bladder irrigation, maybe you can discharge patients earlier with TXA and maybe you have a, it's not just maybe, I'm sure it works.
You have a lower risk that they need to come back to the hospital, the bladder irrigation. It doesn't mean that you should, "Now you have TXA, I don't need to do proper hemostasis." Not at all. So of course you have to do a proper hemostasis. It's just add on. But then the question is all these, for instance, nephrectomy I would recommend. Then when it comes to either like radical prostatectomies and those we had those, we had the most common procedure in our study, but I know that many people think that my bleeding rates are so low. So I mean, look for your own rates. If they really are very, very low, then you don't need. So the question is, really if the baseline bleeding risk is low, you can forget TXA. You don't need it. Vasectomy doesn't need it.
But if you really know your numbers and they are low, then you can forget. But whenever there's anything that you would like to prevent in terms of bleeding, I think you can decrease that risk 33%, not 100, but 33. So if you have a procedure which has a 5% risk, why wouldn't you use it? It comes from five to maybe three point something. Maybe you need to give it to 30 to prevent one major bleeding, but it costs like a couple of euros or dollars. It's so cheap. I don't know in the US, but I'm sure it's not expensive here either. I know in our hospital it costs six euros.
Zachary Klaassen: Wow. That's a great practical application, I think. And this is really what we think about practice changing work. So congratulations on a great trial. Publication European Urology will take the citation to our discussion. Any take home points? Anything we haven't hit on yet?
Kari Tikkinen: I might take point point, I would say that first of all, thank you so much, UroToday, what you are doing. I follow these videos and surely I learn a lot.
Zachary Klaassen: Wonderful.
Kari Tikkinen: From the TXA, I would say, do not worry too much about the thrombosis, that we have now evidence which is high quality, which suggests that it does not suggest. And then when you have procedures for increased bleeding risks, why not use? And especially if the patient cannot be transfused there or if you're in a setting where you don't have a good blood service and especially I think the poor countries in Africa and other areas where there's a huge lack of transfusion, I think tranexamic acid can save lives and can also reduce costs. So it's good for patients and the health systems.
Zachary Klaassen: Wonderful. Well said, Kari, thanks for joining us on UroToday.
Kari Tikkinen: Thank you so much.