complex cases in pci: tailoring antiplatelet...

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Complex Cases in PCI:Tailoring Antiplatelet Therapyto Improve Outcomes CME/ABIM MOC/CE

Supported by an independent educational grant from Chiesi USA


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Complex Cases in PCI: Tailoring Antiplatelet Therapy to Improve Outcomes CME/ABIM MOC/CE

Target AudienceThis activity is intended for cardiologists, surgeons, critical care specialists, nurses, nurse practitioners, and all clinicians interested in antithrombotic therapy and PCI.

GoalThe goal of this activity is to improve clinicians’ ability to manage patients undergoing PCI and the transition from the acute to the chronic care setting and IV to oral therapy.

Learning ObjectivesUpon completion of this activity, participants will:

• Have greater competence related to

– Tailoring antithrombotic therapy for patients undergoing percutaneous coronary intervention (PCI) based on patient and disease characteristics

– Using effective team-based strategies to improve outcomes for patients undergoing PCI

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ABIM MOC

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 0.50 MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Aggregate participant data will be shared with commercial supporters of this activity.

This article is a CME/ABIM MOC/CE certified activity.To earn credit for this activity visit:


CME Released: 3/26/2018; Valid for credit through: 3/26/2019


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Disclosures

Moderator Deepak L. Bhatt, MD, MPH Professor of Medicine, Harvard Medical School; Executive Director, Interventional Cardiovascular Programs, Brigham and Women’s Hospital Heart & Vascular Center, Boston, Massachusetts

Disclosure: Deepak L. Bhatt, MD, MPH, has disclosed the following relevant financial relationships:

Received grants for clinical research from: Amarin Corporation plc; Amgen Inc.; AstraZeneca Pharmaceuticals LP; Bristol-Myers Squibb Company; Chiesi Pharmaceuticals, Inc.; Eisai Inc.; Ethicon, Inc.; Forest Laboratories, Inc.; Ironwood Pharmaceuticals, Inc.; Ischemix, Inc.; Lilly; Medtronic, Inc.; Pfizer Inc; Roche; Sanofi; The Medicines Company

Dr Bhatt does intend to discuss off-label uses of drugs, mechanical devices, biologics, or diagnostics approved by the FDA for use in the United States.

Dr Bhatt does intend to discuss investigational drugs, mechanical devices, biologics, or diagnostics not approved by the FDA for use in the United States.

Panelist Dominick J. Angiolillo, MD, PhD Professor of Medicine; Director, Cardiovascular Research; Program Director, Interventional Cardiology Fellowship, University of Florida College of Medicine, Jacksonville, Florida

Disclosure: Dominick J. Angiolillo, MD, PhD, has disclosed the following relevant financial relationships:

Served as an advisor or consultant for: Amgen Inc.; Aralez; AstraZeneca Pharmaceuticals Inc.; Bayer HealthCare Pharmaceuticals; Biosensors International Group, Ltd.; Bristol-Myers Squibb Company; Chiesi Pharmaceuticals, Inc.; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; PLx Pharma Inc.; Pfizer Inc; Sanofi; The Medicines Company

Received grants for clinical research from: Amgen Inc.; AstraZeneca Pharmaceuticals LP; Bayer HealthCare Pharmaceuticals; Biosensors International Group, Ltd.; CeloNova BioSciences, Inc.; CSL Behring; Daiichi Sankyo, Inc.; Eisai Inc.; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Matsutani Chemical Industry Co., Ltd.; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Osprey Pharmaceuticals USA; RenalGuard Solutions, Inc.

Other: Participation in review activities from CeloNova BioSciences, Inc.; St. Jude Medical

Dr Angiolillo does not intend to discuss off-label uses of drugs, mechanical devices, biologics, or diagnostics approved by the FDA for use in the United States.

Dr Angiolillo does not intend to discuss investigational drugs, mechanical devices, biologics, or diagnostics not approved by the FDA for use in the United States.

SD/Editor/Writer Information and Disclosure StatementsJoy P. Marko, MS, APN-C, CCMEPScientific Director, Medscape, LLC

Disclosure: Joy P. Marko, MS, APN-C, CCMEP, has disclosed no relevant financial relationships.

Christine WelniakFreelance medical writer/editorLos Angeles, CA

Disclosure: Christine Welniak has disclosed no relevant financial relationships.


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Complex Cases in PCI: Tailoring Antiplatelet Therapy to Improve OutcomesDeepak L. Bhatt, MD, MPH: Hello, I am Deepak Bhatt from Boston. I am here today at ACC 2018 to discuss “Complex Cases in PCI: Tailoring Antiplatelet Therapy to Improve Outcomes” with my good friend Dominick Angiolillo, who is Professor of Medicine and Director of Cardiovascular Research and Program Director of the Interventional Cardiology Fellowship at the University of Florida in Jacksonville. That is a lot of different roles that you are holding there. They keep you pretty busy I guess.

OverviewWe have many topics that we are hoping to cover today, but the theme really is antiplatelet therapy in cath lab patients, the transitions from acute to chronic care, intravenous (IV) to oral therapy, and vice versa. We will be going through different antiplate-let strategies for specific patients based on their medical history, disease characteristics, and angiographic findings. We are going to go through some cases to help contextualize all of that.

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Case 1: Antiplatelet Strategy for High-Risk PCI of STEMIOur first case is going to be a patient undergoing high-risk percutaneous coronary intervention (PCI) with ST-segment elevation myocardial infarction (STEMI) and multivessel disease, a situation that comes up not infrequently. Dominick, let me turn to you. What exactly is your strategy for that patient? Obviously quick time to treatment, get them to the cath lab quickly. With respect to antiplatelet therapy, what are you doing with that patient? Do you pretreat that patient with an oral agent? What do you do?

Dominick J. Angiolillo, MD: Yes, at our center now for a number of years we have tried to simplify as much as possible the antithrombotic management of these patients with the goal of getting the patient to the cath lab as soon as possible. When the patient presents to the emergency department (ED) or being transferred from another facility, our recommendation is to get the loading dose of aspirin, give a bolus of unfractionated heparin, and send the patient to the cath lab as soon as possible. We do not pretreat as a strategy with an oral P2Y12 inhibitor. We wait for the patient to come to the cath lab and make our decision-making right there and then.

Dr Bhatt: What is it that keeps you from using an oral adenosine diphosphate (ADP) receptor antagonist? You do not want to use an oral glycoprotein IIb/IIIa inhibitor (GPI) as I started to say. Those definitely did not work. What is the reason not to in this STEMI patient?


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P2Y12 Inhibitor Pretreatment Concerns[1]

Dr Angiolillo: There are a few reasons. One thing that we have learned historically from many STEMI studies, the more you try to do up front, the greater the delay. The real reason is because when you critically look at the data out there, there really is no benefit of pretreatment in the context of STEMI when using even one of the more potent agents. We have what might be the best trial evidence from the ATLANTIC study[1] where, again, the timing of the difference is just 30 minutes. When you look at that timeframe...

Dr Bhatt: Just for the audience, that was ticagrelor up front in STEMI patients.

Dr Angiolillo: Absolutely. It is really not enough time for the drug to kick in.

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Pros and Cons of Upstream vs Downstream Use of P2Y12 Receptor Inhibitors[2]

Dr Angiolillo: When you look at a series of pharmacodynamic studies, and you evaluate actually what is going on, you can see that within the first several hours, 4 to 6 hours, there are a considerable number of patients where the drug has not achieved a full antiplatelet effect. The question then becomes, why even bother for that extra 30 minutes? Just take the time and treat the patient in the cath lab. If we look further into these patients, looking at the pharmacokinetic aspect, in other words, how much drug is actually circulating, we see the same thing. The delayed pharmacodynamic effects are because the drug is not getting absorbed yet. These are STEMI patients where there is delayed absorption. They may be treated with morphine. In the United States, most of our patients are treated with morphine. All of these factors come into play. This is the reason why in our practice we just wait for the patient to come to the cath lab.

Novel Oral P2Y12 Effects in Patients With STEMI[3]

Dr Bhatt: Yes, that makes a lot of sense. I typically take that approach myself. You are right, ATLANTIC was not robustly positive. There were some signals and stent thrombosis, but overall the trial was not positive for pretreatment with ticagrelor. What if the ticagrelor had been crushed? Do you think that then it might have kicked in in time for the procedure?


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Is Drug “Crushing” a Viable Strategy?[4,5]

Dr Angiolillo: It is hard to say. What we do know is that when you crush ticagrelor given in the cath lab, there is obviously a faster absorption, and the same thing happens for prasugrel. These have been shown in the MONITOR and the CRUSH studies, respectively. The CRUSH trial by Dr Rollini from our group also looked at the pharmacokinetic aspect, and you clearly see that there is greater absorption. The problem is that you can crush as much as you want, and again, I am a fan of crushing. I crush regardless, because you always want to get the drug on board as soon as possible. It is not as quick as for example an IV agent. The question becomes, if you do a trial of crushing upstream, would that make a difference? We do not have that data. There is actually an ongoing trial in the Netherlands the CompareCrush actually looking into this specific question.

Dr Bhatt: How about clopidogrel and crushing, any merit in doing that?

Dr Angiolillo: Crushing clopidogrel also accelerates absorption, but I would say in the context of STEMI, clopidogrel is not your drug of choice obviously for the vast majority of patients. It is a little bit less of interest.

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Other Pretreatment StrategiesDr Angiolillo: There is another thing that I did not mention before, which I think is relevant for US practice: the concept of pretreatment in STEMI. There are several nice editorials surrounding the ATLANTIC study on the topic and differences between US and European practices where in the United States you have a large number of false activations. It can vary. You would be pretreating many patients who are actually not having a STEMI, may have a dissection, or may not have anything at all. Again, if you associate the percentage of false activations with the lack of benefit taken together, we just treat it in a cath lab.

Dr Bhatt: Yes, I think that really makes sense. You touched upon something that I think is really important. There is emerging kinetic pharmacodynamic data. You mentioned morphine and delayed absorption. Alfentanil as well in the cath lab, as it turns out, is also doing that. I think most patients with STEMI do end up getting morphine in the ED. Do you use fentanyl in the cath lab? I do not mean just in STEMI?

Dr Angiolillo: Yes, it is actually standard,

Dr Bhatt: Well, it is standard in our lab, too. It turns out many European labs do not actually use fentanyl.

Dr Angiolillo: Years ago, we did not even know about this potential for an interaction. When you think about the lower-risk patients, what are the clinical implications of that slight delay in absorption? It has been shown, even in lower-risk patients, but from a clinical perspective, if there would have been an important impact of that low dose of fentanyl, we would have seen very high rates of thrombotic complications early after stent implantation, which we are obviously not seeing. I feel very comfortable.

Dr Bhatt: I feel the same way. I was going to ask you, especially with your experience of having performed procedures on both sides of the Atlantic, did the fentanyl make a difference? That is, were the patients more comfortable? Is it just unnecessary? Can we just get away with benzodiazepine and midazolam, for example?

Dr Angiolillo: I think there is a clear advantage of keeping the patient as comfortable as possible.

Dr Bhatt: Let us move on now to another case. That was somebody with STEMI in the oral part. We will come back to what happens in the cath lab. Let us say this patient who has come in with a STEMI, has cardiogenic shock. There, what are your concerns with any oral therapy?


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Case 2: Antiplatelet Strategies for STEMI and Cardiogenic Shock[6] Dr Angiolillo: With any oral therapy is the issue of having the drug get from the oral cavity into the gastrointestinal tract. Obviously there we can crush, put it down a nasogastric (NG) tube. There are issues in terms of the way the tablets or even the crushed formulation sticks along any conduit that we are using. Particularly in these patients, I strongly believe in the value of having an IV agent. With the availability of cangrelor, which is the IV version, it is an IV P2Y12 inhibitor, and the ability to also adjust the dose of cangrelor gives much comfort. Some patients may be coming in with cardiac arrest. They may undergo hypothermic protocol. We know that also can have an impact on drug absorption. Again, overall for these critically ill patients, they are already sick enough. If you are performing a high-risk procedure, putting in a stent, you want to make sure that the patient receives the adequate level of antiplatelet effects.

Dr Bhatt: In that patient in shock, who is intubated with an NG tube. What do you do with the aspirin?

Dr Angiolillo: We do the same thing. We still put it down the tube. How much is being really absorbed we do not know.

Dr Bhatt: Do you crush it?

Dr Angiolillo: Yes, unfortunately in the United States we do not have IV formulations of aspirin.

Dr Bhatt: I was going to ask you, because in Europe that is common in some labs.

Dr Angiolillo: Yes, it is common regardless in STEMI, to give an IV formulation whether in shock or not. I wish we would have it in the United States as well, but we do not.

Dr Bhatt: What about per rectum?

Dr Angiolillo: That is also an option. I am not that familiar with the studies looking at differences in terms of antiplatelet effects.

Dr Bhatt: That is the problem. If you are not familiar with it, probably nobody is familiar with it. I was thinking in my mind, I do what you do with respect to the aspirin, crush it, and if they are unable to take it by mouth, and then give it down the NG tube. I have, of course, given per rectum aspirin. I am not really sure how well we know the comparative data between those routes of aspirin.

Dr Angiolillo: I am not that familiar with it. We may need to do a study.

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Dr Bhatt: We will have to give that some thought. That is aspirin that is the ADP receptor antagonist in a shock patient, of course. As you mentioned an IV agent, very attractive. What about a GPI as opposed to cangrelor in the shock patient? We will move back to just a general study patient.

IV Antiplatelet Agents: Cangrelor vs GPIs[7,8,9]

Dr Angiolillo: When it comes to a decision of an IV agent, obviously we have GPIs. We know a lot about them. We have been using them for more than 2 decades. We have our newer agents, a new kid on the block, which is cangrelor. I think it is important to understand that these are 2 very, very different drugs. I think that with cangrelor you have the advantage of targeting the receptor that you want, which is the P2Y12 receptor. There are other differences that I believe are extremely important. First of all, the bleeding potential, although we do not have head-to-head comparisons from large-scale clinical trials. We have wonderful data from your analysis from CHAMPION PHOENIX clearly showing that in patients treated with a GPI there is more bleeding, there are more transfusions. When using cangrelor there is no trade-off in terms of ischemic events. There is the other aspect of dosing. Many times in our acute patients, for example, STEMI coming in, we really do not know much about the patient. With the labs, for example, what is the patient’s renal function? We know that, particularly with the small molecules, GPIs, we do need to adjust the dose.

Dr Bhatt: That is the common source, actually, of error, dosing errors in that situation.

Dr Angiolillo: You do not have that problem with cangrelor. It is an important source of overdosing and bleeding.


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Expert Consensus Recommendations on Switching[9]

Dr Angiolillo: There is the option with cangrelor, for example, in a patient with shock, we can use the standard PCI dose during the first 2 to 4 hours after the procedure. We can bring the dose down to what we call a bridging dose to maintain sustained levels of P2Y12 inhibition. Not extreme levels like in the PCI dosing. I think it is great to transition.

Cangrelor Platelet Reactivity by Day[8]

Dr Angiolillo: You have data from the BRIDGE trial showing that you can continue that infusion for up to 7 days. There is now growing experience and I believe your group actually was one of the first to report on the real-world experience. It is a drug that comes in very handy. Having said this, again, the GPIs have represented a very important component of the pharmacologic armamentarium for patients undergoing PCI. I do believe in striving for a treatment option that can be associated with a lower bleeding potential, but at the same time give an ischemic benefit is obviously welcome.

Dr Bhatt: We were focused on STEMI and cardiogenic shock. Is that the approach you take to STEMI without cardiogenic shock as well? Of course, in cardiogenic shock there is the issue of absorption. STEMI, there is the issue of timing, but absorption, unless they are in shock, presumably would be okay.

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STEMI Without CS: Crushed Oral vs IV P2Y12 Inhibitors[10]

Dr Angiolillo: Yes, good point. In our lab, a little bit more than a year ago, all STEMI patients are treated because as a strategy, we do use cangrelor. As of 3 or 4 months ago, it is not routine for all our STEMI patients simply because now we have a randomized study in STEMI called CANTIC, where patients are being randomly assigned, everybody gets crushed ticagrelor at the time of the start of PCI, and either cangrelor or placebo. The question that you raised before, would crushing make a difference? One can say do you really need to give an IV agent if you can just go ahead and crush? I still think there is a benefit of an IV agent. One may ask, well show me the data. That is the reason why we are doing this pharmacodynamic study. Patients are being randomly assigned. This is a double-blind study.

Dr Bhatt: That is terrific. When do you think it might report?

Dr Angiolillo: I hope to have completed the trial data by the end of the summer or maybe American College of Cardiology (ACC) next year.

Dr Bhatt: That is great. My intuition is the same as yours, but really, we need the data to see. That is clearly a fascinating type of study.


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Propensity-Matched Analysis Comparing Cangrelor Alone vs Clopidogrel Plus GPIs in the CHAMPION Trials[7] Dr Bhatt: What about those folks who counter, you know, you’re right, the GPIs, at least in our propensity-adjusted analysis from the CHAMPION program, were associated with a higher rate of bleeding than cangrelor, similar efficacy. Looked like cangrelor was the more attractive of the 2 options. Sometimes physicians ask what if I am not using the GPI as you were in the trial that is bolus and infusion, but just bolus, no infusion. If there is no complication, done with the GPI, what do you think of that strategy vs a cangrelor-based strategy?

Dr Angiolillo: The truth is, we have very limited data, although it is being performed a lot in clinical practice, it is really not substantiated by any large-scale clinical trial. Again, we have some smaller studies supporting that you are able to have that coverage during the peri-PCI period. Is it necessarily the right strategy? It is true that we have shied away from the traditional prolonged infusion strategies. I think we just need some more evidence. It is not something that I necessarily endorse in my practice because I choose the strategy based on what was shown in the clinical trial.

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Pooled Acquired Thrombocytopenia (TCP): 48-Hour Ischemic Outcomes, Stratified By Acquired TCP[11]

Dr Angiolillo: There is another thing that we do not speak about with GPIs, which actually can happen also with a bolus only, even though it is rare, GPIs are associated with thrombocytopenia. There is actually a very nice analysis coming from the CHAMPION PHOENIX trial coordinated by Matthew Price looking at this and showing that even though thrombocytopenia is rare, but more prevalent in patients treated with a GPI, these patients have a higher risk of adverse cardiovascular outcomes, including mortality. Again, we get back to the question, if you have options, why not use an option for your high-risk patient to minimize as much as possible any adverse outcome?

Dr Bhatt: Yes, that makes sense. I share with you a little bit of hesitancy with the bolus-only strategy GPIs are certainly logical, cheaper theory. It should reduce bleeding compared with an infusion. Really lacks large outcome trials validating that approach. There have been small biomarker studies looking at creatine kinase-myocardial band (CK-MB) release and so forth, but not really a thorough clinical validation, at least in my own opinion.


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Strategies for Patients With NSTEMI and UA[1,12]

Dr Bhatt: What if that patient with myocardial infarction (MI) we just changed to an NSTEMI patient or somebody with real unstable angina, dynamic electrocardiogram (ECG) changes, that sort of thing? Does that change any of your strategies with respect to oral pretreatment? Certainly, studies like CURE and PCI CURE suggested a benefit of a strategy of pretreatment.

Dr Angiolillo: Good question. I think it really narrows down to what is going to be the timing to get to the cath lab. If you have a high-risk, NSTEMI patient, shows up at 4:00 or 5:00 in the morning to your ED, for the most part, those patients will be in the cath lab within 3 or 4 hours, definitely the same morning. There you want to wait, see the anatomy, and make your decision, particularly since you are considering that there are still 10% to 15% of patients who may require bypass surgery.

Dr Bhatt: Every registry is very consistent in the United States. In Europe, that number might be a little low. In the United States, it is consistently 10% to 15% during that index hospitalization going to coronary artery bypass graft (CABG). As interventionalists, we keep talking about how we are pushing the boundaries, but that number has not actually changed that much.

Dr Angiolillo: Exactly, we prefer just to wait to see coronary anatomy. If the patient is coming from an outside hospital, they may already come pretreated. It is not our decision. The not so high-risk unstable angina, NSTEMI may come in on a Saturday morning, we will probably wait until Monday. If it is a high-risk NSTEMI, they get none regardless. If it is a Saturday or a Sunday, whatever it is. You do have those patients, who have a borderline positive troponin, they are overall doing okay. Maybe those patients will be pretreated. For the most part, our practice is not routine pretreatment, which represents what 50% of the United States is actually doing.

Dr Bhatt: Again, the registries are pretty consistent in that 50% range. There is much variation between physicians and centers. Overall, it is right around 50%.

Dr Angiolillo: Again, you did refer to some of the landmark trials, such as CURE. It is also important to recognize that these were studies conducted in a different era with a longer time to delay to get to the cath lab. It was very different from the modern era of interventional cardiology.

Dr Bhatt: If I might add one thing; there is of course the ACCOAST trial. A little bit more contemporary with prasugrel, not with clopidogrel. A well done study and their oral pretreatment did not help at all, but in fact the data safety monitoring boards said stop the trial because of excess bleeding, no benefit. Again, the concept of pretreatment makes sense. There is some suggestive data from an older era with clopidogrel. At least a more contemporary trial with faster time to treatment with a more potent agent prasugrel did not work and the strategy backfired with more bleeding.

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Dr Angiolillo: That is a great point. One can say, can you translate these data using ticagrelor, for example? We do not have the trial, because everybody in PLATO was pretreated. If you believe that the increased bleeding rate is related to the use of a more potent agent, one would say, why should they largely differ? On this background, there were many questions a number of years ago, because if you read the guidelines strictly, it is referred to how the trial was designed. There are questions regarding giving ticagrelor on the cath lab table. We did a study, which was the ad hoc PCI, just to address that question. Obviously, the trial shows that ticagrelor, given in the cath lab, already within 30 minutes will have much more platelet inhibition compared with clopidogrel.

Dr Bhatt: That is the oral pretreatment data in the end STEMI universe. Your strategy in the cath lab for high-risk unstable angina?

Dr Angiolillo: There is much variability, which is very operator-dependent, typically in the patient who is at lower ischemic thrombotic risk just using good old unfractionated heparin and giving the load of one of the newer oral agents in the cath lab.

Dr Bhatt: How about bivalirudin?

Dr Angiolillo: I have actually used less and less bivalirudin now that our lab is exclusively almost all radial, at least 90% radial. Bivalirudin I think is a great drug. Obviously, the benefit of bivalirudin is its ability to reduce bleeding complications. When you look at some of the more recent meta-analyses, much of the bleeding is related to access site. I restrict bivalirudin mostly for my patients who I believe are higher bleeding risk and particularly higher bleeding risk using a femoral approach.

Dr Bhatt: My practice mirrors yours almost precisely. Getting back to the cath lab, in general, is that low-risk patient getting aspirin, heparin, and your ADP receptor antagonist of choice as a load after the procedure is done?

Dr Angiolillo: Yes. Personally, I just give it immediately after the procedure.

Dr Bhatt: You give it after the diagnostic procedure?

Dr Angiolillo: Yes. You know that you are moving forward. It is not uncommon just to do the procedure and give it after the stent is done if it is a simple case. Sometimes you are a lot quicker in doing your procedure than waiting for the nurse to give the load. The patient is lying flat, so you just get the procedure done, particularly if it is a 10- to 15-minute case. That is not going to make a difference.


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Strategies for Complex PCIDr Bhatt: Sure, that is a good point. What about, if taking acute coronary syndrome (ACS) off the table, this complex PCI? I remember a time when I was at the Cleveland Clinic. We were using GPIs in all those patients and then moved away to using it early in none of those patients. What do you do with complex PCI? Of course, whenever you go to the lab, every outbreak, I am doing a lot of complex PCI, but I mean really complex (ie, heavily calcified, bifurcation, left anterior descending [LAD] diagonal lesion).

Dr Angiolillo: What about for a longer procedure like a triple vessel disease patient? These are the patients where I am using more bivalirudin if I am not going to be using an IV antiplatelet. The reason is because I will start the bivalirudin infusion and I will have to think about activated clotting times (ACTs).

Dr Bhatt: It is a practical advantage.

Dr Angiolillo: It is just a practical advantage. Do your case and you already have a lot to think about. Keeping a bivalirudin infusion helps you out. I believe there is also a component of complexity in terms of calcification or bifurcation, a lot going on. This is a case where I consider cangrelor on top of unfractionated heparin. There is some interesting analysis coming from CHAMPION PHOENIX, which I believe was presented at a Transcatheter Cardiovascular Therapeutics (TCT) meeting. Looking at complexity and the magnitude of benefit of having an IV antiplatelet on board such as cangrelor, I do not use a GPI in those situations.

Dr Bhatt: Before we close, just one point; we have talked a bit about cangrelor and some of the audience may be familiar with it, maybe you are not. If an operator chooses to use it, there are some things to know. You have done some beautiful work. For those listening at home, I would say look at the data. You will see beautiful work in terms of receptors, binding, and oral agents in cangrelor and theoretical concerns, at least for interaction. Could you just in 30 seconds say what the bottom line is in terms of which agent can you give, in what order?

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Cangrelor to Thienopyridine Transition[13]

Dr Angiolillo: Within the trial, clopidogrel was the oral agent that was used, and it was given at the end of the cangrelor infusion. The reason is that there is a drug interaction. In other words, if cangrelor is already on the receptor, clopidogrel, if given at the time of the infusion, will not be able to bind its active metabolite. You need to give it at the end. That is also what is in the package insert. The same happens for the other thienopyridine, which is prasugrel. The active metabolite is unstable. In addition, prasugrel is given at the end of the infusion.

Dr Bhatt: Is it a loading dose of 600 mg of clopidogrel or loading dose of 60 milligrams of prasugrel?


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Cangrelor to Ticagrelor Transition[13]

Dr Angiolillo: With ticagrelor it is different, because being the drug with a longer half-life, you can give it essentially at any time before, during, or after the cangrelor infusion, because what happens to the ticagrelor drug is wandering around while the cangrelor is occupying the receptor. As soon as the offset of cangrelor occurs, then ticagrelor can bind to the P2Y12 receptor. I can say in my clinical practice, when I am using cangrelor in my ACS patients, ticagrelor is typically my drug of choice, because I call it the more cangrelor-friendly agent. You can give the drug in the cath lab. You do not have to worry about the patient going to the cardiac care unit (CCU), and explaining to the nurse, give the loading dose at the end of the infusion. You just want to take care of things right there in the cath lab.

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Team-Based StrategiesDr Bhatt: Yes, that is great advice. If you are going to use the other agents, I think it is important for there to be clear algorithms at the hospital what to give, when to avoid any potential drug interaction.

This has been a terrific discussion. I have learned a lot from you as I always do. I hope that the audience enjoyed it too. Hopefully, all different members of the healthcare team are listening. Much of what we were discussing in terms of transitions of care, switching from the IV to the oral agent, trying to avoid interactions, much has to do with patient safety there. Nurses, nurse practitioners, and pharmacists really play an integral in part and in transitions of care as well as removing patients from the cath lab to the CCU, to the recovery room, or to the telemetry floor. It is very important for all those different types of healthcare providers to understand the intricacies, even right down to the pharmacokinetics and pharmacodynamics of these different drugs.

For all of you who are listening at home while we are here having fun in the sun in Orlando (actually, it has been a little cool in Orlando), thank you for listening. I hope that it was educational for you. Thank you for participating in this CME activity.

This transcript has been edited for style and clarity.


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References1. Capadanno D, Angiolillo DJ. Pretreatment with antiplatelet drugs in invasively managed patients with coronary artery disease in the contemporary era: review of the evidence and practice guidelines. Circ Cardiovasc Interv. 2015;8:e002301.2. Capodanno D, Angiolillo DJ. Reviewing the controversy surrounding pre-treatment with P2Y12 inhibitors in acute coronary syndrome patients. Expert Rev Cardiovasc Ther. 2016;14:811-820.3. Alexopoulos D, Xanthopoulou I, Gkizas V, et al. Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in patients with ST-segment-elevation myocardial infarction. Circ Cardiovasc Interv. 2012;5:797-804.4. Rollini F, Franchi F, Hu J, et al. Crushed prasugrel tablets in patients with STEMI undergoing primary coronary intervention: the CRUSH study. J Am Coll Cardiol. 2016;67:1994-2004.5. ClinicalTrials.gov. CRUSHed vs. Uncrushed Prasugrel in STEMI Patients Undergoing PCI (CompareCrush). NCT03296540. https://clinicaltrials.gov/ct2/show/NCT03296540. Accessed March 21, 2018.6. Bhatt DL, Stone GW, Mahaffey KW, et al. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med. 2013;368:1303-1313.7. Vaduganathan M, Harrington RA, Stone GW, et al. Evaluation of ischemic and bleeding risks associated with 2 parenteral antiplatelet strategies comparing cangrelor with glycoprotein IIb/IIIa inhibitors: an exploratory analysis from the CHAMPION trials. JAMA Cardiol. 2017;2:127-135.8. Angiolillo DJ, Firstenberg MS, Price MJ, et al. Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial. JAMA. 2012;307:265-274.9. Angiolillo DJ, Follini F, Storey RF, et al. International expert consensus on switching platelet P2Y12 receptor-inhibiting therapies. Circulation. 2017;136:1955-1975.10. ClinicalTrials.gov. Platelet Inhibition With Cangrelor and Crushed Ticagrelor in STEMI (CANTIC). NCT03247738. https://clinicaltrials.gov/ct2/show/NCT03247738. Accessed March 21, 2018.11. Price MJ, et al. Circ Cardiovasc Interv. 2018. In press.12. Gu YL, van der Horst ICC, Douglas YL, et al. Role of coronary artery bypass grafting during the acute and subacute phase of ST-elevation myocardial infarction. Neth Heart J. 2010;18:348-354.13. Rollini R, Franchi F, Angiolillo DJ. Switching P2Y12-receptor inhibitors in patients with coronary artery disease. Nat Rev Cardiol. 2016;13:11-27.14. Fan W, Plent S, Prats J, et al. Trends in P2Y12 inhibitor use in patients referred for invasive evaluation of coronary artery disease in contemporary US practice. Am J Cardiol. 2016;117:1439-1443.

AbbreviationsACC = American College of CardiologyACS = acute coronary syndromeACT = activated clotting timeADP = adenosine diphosphateCABG = coronary artery bypass graftCCU = cardiac care unitCK-MB = creatine kinase-myocardial bandCS = cardiogenic shockECG = electrocardiogramED = emergency departmentEMA = European Medicines AgencyFDA = US Food and Drug AdministrationGPI = glycoprotein IIb/IIIa inhibitorHCP = healthcare provider IDR = ischemia-driven revascularizationIV = intravenousLAD = left anterior descendingMACE = major adverse cardiovascular eventsMI = myocardial infarctionNG = nasogastricNSTEMI = non-ST-segment elevation myocardial infarction OR = odds ratioPCI = percutaneous coronary interventionPS = propensity scoreRCT = randomized controlled trialST = stent thrombosisSTEMI = ST-segment elevation myocardial infarctionTCP = thrombocytopeniaTCT = Transcatheter Cardiovascular TherapeuticsUA = unstable anginaUS = United States

https://clinicaltrials.gov/ct2/show/NCT03296540

https://clinicaltrials.gov/ct2/show/NCT03247738

complex cases in pci: tailoring antiplatelet...

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