Speaker 1 00:05 Lange, welcome to HelixTalk, a podcast presented by the Rosalind Franklin University College of Pharmacy. Narrator - Dr. Abel 00:11 This podcast is produced by pharmacy faculty to supplement study material and provide relevant drug and professional topics. Speaker 1 00:19 We're hoping that our real life clinical pearls and discussions will help you stay up to date and improve your pharmacy knowledge. Narrator - Dr. Abel 00:27 This is an educational production copyright Rosalind Franklin University of Medicine and Science. Speaker 1 00:32 This podcast contains general information for educational purposes only. This is not professional advice and should not be used in lieu of obtaining advice from a qualified health care provider. Narrator - Dr. Abel 00:47 And now on to the show. Dr. Sean Kane 00:51 Welcome to HelixTalk. Episode Four. My name is Dr. Kane, and I'm Michael Schuman, and I'm Dr. Patel, and today we're talking about P2Y12 inhibitors and antiplatelet agents. The first agent we're talking about today is Plavix. The generic name is clopidogrel, and this is one of the older ones on the market. Speaker 2 01:09 Dr. Schuman, what is this? Clopidogrel is used in Speaker 3 01:13 this is one, as with some of the others. It can be used a couple different disease states, of course, all relating to cardiovascular health. So acute coronary syndrome, myocardial infarctions, strokes or peripheral artery disease are kind of the main areas in which it's used. Dr. Sean Kane 01:26 Sounds like it's approved for quite a few different things. At least in the ICU, the most common indication I see it for is someone who's had a cardiac stent where they had a heart attack, they got a stent placed, and now they're on this medication for a few months, depending on the type of stent that was placed. And I guess we should kind of clarify how these agents actually work, so they are anti platelet agents. But I think we can do better than that in terms of how they work. Speaker 3 01:50 So they're antiplatelet in the sense that what they do is they block what's called ADP, P2Y12, and it's a receptor on these platelets, so that, by blocking that, it then allows for with a decrease in aggregation, and just to allow platelets instead of that clumping. So it's not working to directly block some of the anticoagulation cascades, like was seen with warfarin. It's not blocking thrombin, as is seen with some of those newer anticoagulant medications. When I was first learning about this one in school, one of the things that came out was the concern with some some potential drug drug interactions, especially with medications that inhibit cytochrome P450, the enzyme system, 2C19 and a couple of the medications we learned that were primarily problematic were going to be either omeprazole or esomeprazole, two fairly commonly used medications for either stress ulcers, or just for somebody who who has GERD. Speaker 2 02:46 So then let's say Dr. Kane, if you had a patient who came in to the emergency room and I see you eventually and is on omeprazole, and they're they're placed on clopidogrel, so what will be your step? How would you intervene for this drug interaction? Dr. Sean Kane 03:01 Yeah, so right now, it's an incredibly controversial issue, so the data when it first came out with this drug interaction was what's called a retrospective cohort analysis, which just means that they took people who were on omeprazole, who got Plavix, and compared them to people who were not taking omeprazole, who also got Plavix. What they found was it looked like Plavix was less effective if you were on omeprazole. But the problem with that is that people who tend to take omeprazole tend to be sicker, patients, maybe have more comorbidities, who are more at risk for having problems on their own, maybe independent of the drug interaction itself. So after that, there was a drug study that was supposed to be conducted to kind of be the definitive answer to this question, and it ended up that they were underpowered and lost funding, and they weren't able to kind of definitively answer the question. So right now, we're kind of in limbo, and it's one of those things that typically it's kind of patient specific decision whether or not you can use an alternative PPI proton pump inhibitor for the patient, if you can tolerate an h2 blocker, like for modidine or Ranitidine, or you just kind of ignore the interaction and say that you're comfortable with the potential for that interaction. Speaker 2 04:12 And if I'm not wrong, FDA had put out a statement saying that they would back up if you were to switch your omeprazole to a less inhibitory PPI agent, which is pantoprazole. So I've seen that institutions changing their omeprazole to either pantoprazole or rabeprazole. Correct? Dr. Sean Kane 04:32 There's one thing that I think is important with clopidogrel. You know, we've been talking about this drug interaction, and clopidogrel itself actually has to be activated in the body before it can inhibit the platelets, like we've been talking about. So it uses 2c 19, which is a hepatic enzyme, to activate itself to the point where it can inhibit a platelet. There's two problems with that. One, we already talked about the drug interactions with it. But two, there's a ton of patient inter patient variability, where some patients. Are really, really good at activating this pathway. Some patients are really not good at activating this pathway. Speaker 2 05:05 So what is this phenomenon called Dr. Kane? So it's Dr. Sean Kane 05:09 a genetic polymorphism, which just means that if you take 100 people in a room with different backgrounds in terms of ethnicity, some of them will have polymorphisms or differences in their gene makeup that make up this 2c 19 enzyme system. Speaker 2 05:23 So then, if I'm getting this correct, it kind of leads into direction of checking their enzyme activity. Do we do this test in all the people? Dr. Sean Kane 05:31 So there are genomic tests that are available, but it's not commonly done. There's even platelet tests that are available, but again, not commonly done. The other Speaker 3 05:39 thing I was saying that we kind of touched on is this medication is used with aspirin, right? One thing I know is there's, there's a couple different doses of aspirin that are seen. You know, you have people that take 320, fives of aspirin, maybe even take a couple of those. Then you got that little baby aspirin that's kind of peppered in there for individuals who have a high risk of cardiovascular outcome. So what kind of doses are we talking about when we're when we're using aspirin Speaker 2 06:01 here, so most of the time I've seen especially for the secondary stroke prevention, it's been used with aspirin. We see the aspirin 81 milligram along with the 75 milligram coping drug once a day regimen. Dr. Sean Kane 06:13 And actually, this question was investigated in a trial called the Oasis seven trial, which was a two by two factorial study, which just means that they had kind of four different groups that they were looking that they were looking at, low and high dose Plavix and low and high dose aspirin. What they found was that aspirin, 81 milligrams was equivalent in efficacy and safety to a higher dose, 300 to 325 milligram aspirin, and that was in patients who had a stent place because they had a myocardial infarction. It's important to know that once a patient is on an agent like ticagrelor, it stays on for a while. So a very common scenario is a patient will be taking Plavix, and they need to have heart bypass done or open heart surgery done, and those patients, we have to wait anywhere from five to seven days in order to open them up, because the drug effect can really last that long. So because of a lot of the limitations that we talked about with clopidogrel, the next agent on the market, that is a P2Y12 inhibitor, was prasugrel. The brand name is Effient. Speaker 2 07:15 So what is so special about prasticle? Dr. Schuman? Speaker 3 07:19 Both agents are similar in that they're approved for NSTEMI and STEMI in patients who received a PCI or percutaneous coronary intervention, also known as the stent. But there are some differences in them. Prasugrel is superior in efficacy to clopidogrel, but it does have a higher risk of bleed. And the other advantage with it is it doesn't seem to have as much interpatient variability in terms of the hepatic enzyme, so thus you're at a lower risk of maybe some of those drug drug interactions, if you were especially concerned with it relating to those proton pump inhibitors. Dr. Sean Kane 07:49 I think that's an important point, that the primary area of study for prasogreal is patients who had a stent because they had a heart attack, whereas with clopidogrel, we saw it for a lot of different things, everywhere, from stroke to peripheral vascular disease to our Mi patient who didn't have a stent, necessarily. So this is a more narrow spectrum in terms of where it's been studied. Doesn't mean that it won't be used for other indications down the road, but it's a newer agent, and it hasn't been as extensively studied as clopidogrel or Plavix has. Speaker 2 08:19 Okay, so you're talking about the study, and that's the Timmy 38 trial, right, correct. Dr. Sean Kane 08:24 So the TRITON-TIMI 38 study compared clopidogrel or Plavix versus prasugrel or Effient in patients who had a stent placed because they just had a heart attack. Unknown Speaker 08:34 And what were the outcomes of the study? Speaker 3 08:37 So the TRITON-TIMI study, what it found was that in favor of prasugrel, there was a benefit in cardiovascular death, MI and stroke, and they said the number needed to treat was 46 so you treat 46 people, and you see one additional event that is prevented, and then the other side of the coin was that the TIMI major hemorrhage or type of bleed was higher with prasugrel as well. Dr. Sean Kane 09:04 So we have less clotting in terms of MI and stroke, but we have more bleeding with prasole, just a little bit less in terms of our benefit. Speaker 3 09:12 And I believe that there were a couple other things they did note with that is maybe some out some smaller groups that you may want to be careful of in selecting so people with old age, maybe underweight patients that may not have been as much of a benefit. So you may want to be careful in terms of which agent you select or even what dose you use. Dr. Sean Kane 09:29 Absolutely so because of the Triton can be 38 study. They actually have specific dosing recommendations for those who are underweight, less than 60 kilos older age, greater than 75 years of age, and they say that you should basically use half of a normal dose, so five milligrams instead of 10 milligrams. One interesting Speaker 2 09:47 thing about this medication is that it is contraindicated in patients but previous transient ischemic attacks or stroke. So once again, to reiterate the point, this is a very specific. Niche where you can use prasogrel, I Dr. Sean Kane 10:03 think that's interesting, because we just talked about how clopidogrel, we can use it for secondary prevention of stroke, whereas with prasogrel, it's contraindicated in anyone who's had a history of TIA or stroke, because they do worse on the agent. So one thing to note is, even though we have this different dosing, the half of a dose, the five milligrams per day, despite that, the FDA actually recommends generally avoiding this medication in those who are underweight or older age, because of the fact that they didn't do as well as people who were normal aged, normal weight in the Triton temi 38 study, just like clopidogrel, it's going to be about seven days that you should be holding the agent before a major surgery. So then, after all of this, a third agent came to the market that really made things even more complicated. And that third agent is called ticagrelor. The brand name is brilenta, any Unknown Speaker 10:53 difference in terms of what this one is used for. Speaker 2 10:55 So this one is also studied in patients with acute coronary syndrome, obviously, along with aspirin, and we have more to talk about that aspirin dose in a little bit, but it showed a reduced risk of cardiovascular death, MI, stroke and even thrombosis when it was studied against a combination of clopidogrel and aspirin. It's important Dr. Sean Kane 11:17 to note that in this study, which we'll later to talk about was the PLATO study. If you had an MRI, you didn't necessarily have to have a stent to be enrolled in the trial, whereas with prasogrel, you had to have a stent to be in the trial. Speaker 3 11:30 So I think a couple of the populations in particular that this agent may be beneficial for are those that have failed a combination of clopidogrel plus, again, that low dose aspirin, or for patients who have that reduced P2Y12 inhibition with clopidogrel, whether it's because they're on a medication, such as, again, esomeprazole or omeprazole, or if they have that polymorphism. Speaker 2 11:51 So Dr. Kane, you mentioned the PLATO trial, and if I remember correctly, the findings from the PLATO trial, we saw the composite endpoint of CV death, MI and stroke in favor of ticagrelor, where the number needed to treat was 53. Again, this study was done to test it against the combination of clopidogrel and aspirin. Even ticagrelor showed mortality benefit alone, so not just the composite endpoint. The good thing about this study, opposite of what we found in the prasugrel TRITON-TIMI 38 trial, is that there was no difference in major hemorrhage or major bleeding between the two groups. Speaker 3 12:30 So whereas with with prazi Girl, you kind of had to take the good and the bad, that it was better in terms of, kind of having some of the outcomes in terms of cardiovascular benefit, but then you have an issue with bleed, so this one, you can maybe get a little bit of that increased benefit, but then we're not as much concerned about well, what is it bringing with it to the party, in terms of risk of bleed, exactly? Dr. Sean Kane 12:50 And that's a really big deal, because many of these patients who have mis are going to be of older age, typically they're going to have more comorbidities, and typically they're going to be at a higher risk for bleeding than kind of your run of the mill patient who's otherwise healthy. Speaker 2 13:04 And you have to remember that ticagrelor is studied in combination with aspirin as well. So these two groups were either clopidogrel plus aspirin or ticagrelor plus aspirin. Dr. Sean Kane 13:16 And I think it's worth noting that although the main bleeding endpoint in Plato was no different between ticagrelor and clopidogrel. Some of the other secondary bleeding end points did show that ticagrelor may be associated with a little bit more bleeding, but it really depends on what endpoint and how you define bleeding and things like that. So certainly not benign, but it's probably fairly comparable to clopidogrel. Okay, so it Speaker 3 13:39 sounds like we got some some good information about this medication. What are the potential drawbacks? Because right now, to me, it sounded like this one, especially if you if you fail, copied role, then this one's a pretty good option. Dr. Sean Kane 13:49 Well, just like prasugrel or Effient; ticagrelor or Brilinta is the brand name, so for some patients, it may not be covered under insurance, or if it is covered, their copay may be high. Or if they're a cash payment patient, they'll definitely pay more money for ticagrelor or Brilinta than they would for Plavix or clopidogrel. Speaker 2 14:06 I think the other thing that struck me that is a little bit negative about this medication is twice a day dosing that definitely impacts the compliance, besides just the side effects of bleeding. Obviously, these are platelet inhibitors. We have seen additional side effects for tocagler, and these are pretty interesting. We found in the studies that patients also showed symptoms of ventricular pauses were noted three seconds or larger in the first within first week of therapy. Things like trouble breathing, dyspnea and gynecomastia were also noted. Dr. Sean Kane 14:39 I think that that's a pretty big deal side effect, given that we're giving this medication to someone who's just had a heart attack, and we're saying that they're at risk for bradycardia, specifically ventricular pauses that last more than three seconds, and dyspnea, which we see those things as negative things that happen to patients who have had heart attacks. So this is definitely something that we're going to be wanting to watch in Phase four studies to see how common is this adverse effect. Does it lead to more testing of the patient? Do they have to stay in the hospital longer when they do have these adverse effects because of the thought of, well, is it the Brilinta that's causing it, or is their heart condition getting worse? And sometimes it's hard to distinguish the two, Speaker 3 15:21 and then the gotcha question you asked was a kind of more on the side, and more of an unusual side effect potentially with this medication. But I know that's with gynecomastia, meaning a painful increase in the amount of breast tissue. I know that's one that could, when somebody notices that, lead to a pretty quick discontinuation of a medication, and thus you're maybe opening yourself up for some side effects from stopping Dr. Sean Kane 15:43 so there is one really interesting thing about ticagrelor that happened in the PLATO trial. So when Plato was published, it looked like it was profoundly awesome, finding that we had better efficacy and no risk of bleeding higher than what we saw with clopidogrel. But unfortunately, something bad happened. Brilinta didn't work as well in North Americans as it would in, let's say, a European patient. And why would that be? Well, we weren't really sure, and we probably still aren't completely sure. They did subgroups of the subgroup analysis to see what was different in how we treated a North American patient who received Brilinta versus a European patient who received Brilinta. So they looked at everything from what types of stents we use to what kind of diet a typical North American has to our genetic makeup that may impact how we metabolize off the drugs. And they ended up with this aspirin dosing explanation in terms of why the drug doesn't work as well in North America. And so the conclusion was, so they concluded that it must have just been because in America, or in North America, we use bigger doses of aspirin. In the perimi setting, 325, milligrams, typically, whereas in Europe, they typically used the lower aspirin doses of 81 milligrams. Speaker 2 16:58 And so now going forward, I believe the recommendation is that if in a North American patient population, if you are going to use ticagrelor, you need to keep the aspirin dose to either 81 milligram or at least less than 100 milligram. Dr. Sean Kane 17:13 And really, the problem with this is that we don't know for sure that the aspirin dosing was the thing that got the North American patients up in arms, if you will. It could have been a number of other things that make ticagrelor not as efficacious in North America, and we don't really know what that is. So certainly, with phase four trials, I think people are going to be very interested to see if this lower aspirin dosing really makes a difference, or if we still see this lack of effect in North America, as opposed to the rest of the world. Speaker 3 17:43 And I think the other thing too, that I did notice, I believe, is that the washout period if correct me, if I'm wrong, is a little bit shorter. So this one, in terms of being if you're going in for procedure, this one, we're looking at a five day window, versus maybe that five to seven, or even seven that was seen with with Praza girl or Effie. Dr. Sean Kane 18:00 So to this point, especially with the latter two agents we've talked about, these have been exclusively used as what's called dual antiplatelet therapy, or DAPT. What that means is that we're giving aspirin in conjunction with prasogrel or ticagrelor. For most indications, we're also giving clopidogrel with aspirin. But it depends on the indication. In terms of this dual antiplatelet therapy, it's best studied when a patient has a cardiac stent placed in the post-MI setting. Typically, how long do they need to continue these agents? If they've had a stent placed, in terms of continuing both aspirin and one of these P2Y12 inhibitors? Speaker 2 18:35 And that is a huge controversy. We have plenty of trials that have come out recently that would give us one way or the other evidence. So you kind of have to look at what kind of stent is patient getting. Okay, we do know that we have two different type of stents. We have the bare metal stent, which doesn't include any drugs in it, and we do have the drug eluting stents. So the drug eluting stent would have a layer of medication embedded into the stent that would release in the bloodstream over the time to keep that blood vessel patent, and the kind of medications that they use in this drug eluting stents as Paclitaxel, or we also see things like techrollamus. So what Dr. Sean Kane 19:20 you're saying is that we have two different types of stents, one that doesn't have any drug in it, and another that elutes drug, wherever you put the stent. And you're saying that the duration of dual anti platelet therapy may differ between the two types of stents. That is definitely what I was getting at. Yeah. So how long do we have to continue this dual anti platelet therapy with each of the types of stents? Speaker 2 19:39 So the data with the bare metal stent is a little bit more definitive. Came out of the CREDO and PCI-CURE trials, and the recommendation is that the risk of thrombosis in patients who get bare metal stent decreases after 30 days of the stent placement. So what we're going to do is keep these patients on the combination antiplatelet therapy for at least one year. Speaker 3 20:06 And that's, I think, an important point for any kind of consumers. These are things that needs close following. So these are not a medication you can kind of take it easy and lose to follow up. These intervention need to be made pretty early after stenting has occurred, and then keep it on for a period of time. So if you kind of come back and start one of these, and maybe for these, and maybe for the provider, so if you come back and start one of these way months down the road, it's a little bit unclear whether or not that's going to get quite the same benefit had you started it much, much earlier. Dr. Sean Kane 20:32 So Dr. Patel, with that bare metal stint, you said the risk of thrombosis decreases after a month, but the recommendation is a year. How does that compare to a drug eluting stent? Speaker 2 20:42 The drug that's used in the drug eluting stent differs it whether it's, you know, three months after it decreases the risk of thrombosis, or whether it's six months after it decreases the risk of thrombosis. And the drug eluting stent is the problem area. We really do not know how long the dual anti platelet regimen should be continued in this patient. I know Speaker 3 21:03 that there were some studies that said it's, it's the dual is not really even better than aspirin alone if it's used for 12 months. And then there's others that said, Well, no, actually you can get a benefit from that, that dual therapy as long as 24 months out. So you know, it's one of those. You got a couple different, different families of thought on that. So who do you guys follow? Speaker 2 21:21 Well, so far, that's the evidence available. But the good thing is, the new studies are going on as we speak, as we record this podcast right now. So for now, the recommendation is that patient who is at high risk of thrombosis, post getting the DES, one of the DS dones, we need to continue patient non dual antipode therapy indefinitely, until we see the results of these new trials coming available. Dr. Sean Kane 21:46 And certainly it comes down to kind of a patient specific decision too. So if a patient is at high risk for bleeding, then you may consider discontinuing the medication earlier than normal. Or if a patient is at very high risk for having a secondary heart attack, you may consider leaving them on despite a higher bleeding risk, and it really depends on the patient. I think Unknown Speaker 22:06 that is true. All Speaker 3 22:07 right, so we've got these, this dual antiplatelet therapy now, if there's somebody that's at a high risk, or is there a way to kind of up the ante even further than that, so Dr. Sean Kane 22:19 what you find is, if a patient has a different indication to receive an anticoagulant. So if they have afib, if they have a DVT or a PE, we end up with something called tote, which is triple oral anti thrombotic therapy. And that means that we're giving them dual anti platelet therapy plus an anticoagulant. And as you can probably guess, these patients are at very high risk for bleeding because of their tote therapy. Speaker 2 22:41 So when we talk about this tote therapy, what agents are we talking about in particular? Dr. Sean Kane 22:46 So typically this is going to be aspirin, clopidogrel, and the more frequent. But because of the novel oral anticoagulants that we've discussed in our previous podcast, we're going to be seeing more of an aspirin, a P2Y12 inhibitor, like any of the three talked about today, and then maybe a NOAC. In addition to that, Speaker 2 23:03 what I'm understanding is that the evidence from nowac is still pretty new and emerging, and we do have noticed increased risk of bleeding in the evidence that's available so far. So are you saying that we better stick with Warfarin until more evidence is available? Dr. Sean Kane 23:19 Absolutely Regardless, these patients are going to be at a very high risk for bleeding, and many patients who would normally be indicated for tote will not receive tote because of their bleeding risk. And just to give you an idea of the risk of bleeding, if you looked at patients who had an MI and were put on tote therapy compared to aspirin alone, their bleeding risk is about three times higher than someone who is just taking aspirin without dual anti platelet therapy or even triple oral anti thrombotic therapy. So these patients are definitely at a high risk for bleeding. But sometimes the risk of clot outweighs that risk of bleed, and it's an adverse effect that you're willing to take on, especially in someone, let's say, with a mechanical heart valve where you absolutely have to anticoagulate them. Speaker 2 24:04 Yeah, and do understand that the evidence that's available to use TOAT therapy is mainly from retrospective analysis. We had one randomized trial that was going to evaluate this combination regimen. However, the trial was underpowered, so we don't know if we can rely on the results from that trial. Speaker 3 24:23 And I know when I hear somebody mention warfarin, the question always comes to my mind is, what is our INR target? Are we talking two to three, 2.5 to 3.5 or even? Are we looking at different numbers within those ranges? Speaker 2 24:36 So that's a great question, because, like we mentioned already, their leading risk is very high. So if we are having a patient on warfarin on top of competitor and aspirin, we try to keep the INR Range as tight as possible. So if the patient's goal is two to three, we try to keep them between 2.0 to 2.5 Speaker 3 24:56 that's that's going to be, that's going to be a little tricky. I know that in ranges from. Two to three about some of the retrospective studies I've looked at, you can only keep somebody within range of about 50% of the time. So that's certainly that tight control it's you're gonna have to be real careful to make sure you've got it in even that little smaller parameter there. Dr. Sean Kane 25:13 So Dr. Patel, if we were to go to, let's say, the ACCP chest guidelines, what would we find for things like tote or even our dual anti platelet therapy? Speaker 2 25:22 Great question. So hccp published their new guidelines in 2012 and they did include tote therapy, especially for patients who have afib. So they're using the warfarin for afib, and they have a state placement that requires the dual anti platelet therapy, which is copied girl and aspirin. And again, they recommend that the patients they're looking at, the AFib patient, their chat score, or chat two score, is greater than one. And so for patient who get the bare metal stent, they recommend the tote therapy for at least the first month. Patient again, who have the drug eluting stent, they recommend the therapy to continue for at least three to six months. And patients who are at high risk of late stent thrombosis, they recommend to continue the therapy for 12 months. And when I say high risk of thrombosis, stent thrombosis, those are the patients who have other atherosclerotic indication, things like diabetes, or if they have coronary, acute coronary symptoms at the presentation, or narrow diameter target muscle. So to get the point out of TOAT therapy, we want to make sure that the P2Y12 agent that you're using is clopidogrel, because that's the one that's most studied, either in retrospective trials or in the one prospective trial that we had. We have to make sure that we limit the aspirin dose to 81 milligram, because there is just a lot of anti platelet activity and anti coagulant activity going on. We have to tell the patient that their bleeding risk is higher, as we discussed earlier, so tell them to avoid any Ansett therapy as if possible. Dr. Sean Kane 27:03 And then what about in patients who either have peptic ulcer disease or have had prior gi bleeds, or were just concerned about a GI bleed in that patient because of tote therapy, in Speaker 2 27:13 that case, we would go ahead and add ppi, obviously, because we were using cupidrove, you would want to avoid using omeprazole as omeprazole, so we can go ahead and add pentoprosyl or reprisal for gi protection. Dr. Sean Kane 27:28 So it seems like tote therapy kind of the take home points are that we have a higher bleeding risk, but it's really for a very specific patient population who is at a high clotting risk anyway, Speaker 2 27:38 and for a specific time period, like we mentioned, according to the chest guideline, gotcha. Dr. Sean Kane 27:42 And then also, we can't just willy nilly pick whatever P 2y 12 inhibitor or anticoagulant we like, Right, correct. Speaker 2 27:51 So again, the choice of P2Y12 is clopidogrel, and the choice of anticoagulant is warfarin. Dr. Sean Kane 27:56 So as a review, we covered P2Y12 inhibitors, the first one is clopidogrel, or Plavix, and the thing that I remember about Plavix is that we have a lot of genomic variability and also drug interactions that makes it so that Plavix doesn't get activated. Speaker 2 28:10 Talking about Effient Dr. Kane, I think one thing that I really struck out to me is making sure we're not using it in patients who weigh 60 kilogram or less, or who are age of 75 or greater, Dr. Sean Kane 28:25 then the big thing with prasugrel or Effient is that you cannot use it in patients who have a previous history of TIA or stroke. With ticagrelor or Brilinta, we have very specific aspirin dosing that comes from kind of strange subgroup analyses of North American patients who took ticagrelor/Brilinta. So currently, the best recommendation is that you should never exceed 100 milligrams of aspirin per day. Speaker 2 28:50 And those were the individual P2Y12 inhibitors that we discussed. As far as looking at the dual antiplatelet therapy, the things that we need to remember is that you have to consider what type of stent patients getting. If they have bare metal stents, we recommend at least one year of dual antiplatelet therapy, and if they have the drug eluting stent, yeah, the data is not really clear, and other trials are coming around, so we should keep them on indefinite dual antiplatelet regimen. Dr. Sean Kane 29:19 Then finally, if we really want to have fun, we can start triple oral antithrombotic therapy or TOAT therapy. That means that we're combining aspirin plus clopidogrel or Plavix plus warfarin, and we're not going to be picking any of our other P2Y12 inhibitors. We're not going to pick any of our NOACs or other anticoagulants. And the most typical patient who may receive TOAT therapy is someone who has atrial fibrillation, who needs warfarin, plus someone who had a stent placed because of an MI, and those patients will be on the aspirin, clopidogrel, warfarin combination. Speaker 2 29:51 And rule of thumb is we want to keep the therapy as short as possible and warn the patient of complications, such as increased risk of bleed. Thing. Dr. Sean Kane 30:00 So with that, we'll go ahead and conclude today's podcast. If you want to see any of our other podcasts, you can find us in iTunes under the name HelixTalk, or visit us at HelixTalk.com, I'm Dr. Kane. I'm Dr. shoeman, Speaker 2 30:13 and I'm Dr. Patel, and as always, please study hard. Narrator - Dr. Abel 30:19 Thank you for listening to this episode of HelixTalk. For more information about the show, please visit us at HelixTalk.com. You.