foreign hello welcome to this anticoagulation Forum webinar on perioperative management and anti-thrombotic therapy the 2022 American College of Chess Physicians clinical practice guidelines my name is Jeffrey Barnes in addition to being an AC foreign board member I'm also a cardiologist in vascular medicine specialist at the University of Michigan and I'm thrilled today to be joined by three experts in the space of perioperative anti-thrombotic therapy and members of the guideline writing committee who are going to help us talk through what these new guidelines have to share our first panelist is Dr Jim duquettes who's professor of medicine and vascular medicine as well as the David Bradley and Nancy Gordon share in thrombotic medicine at McMaster University in the Hamilton Health Sciences St Joseph Healthcare System Jim thanks for joining us today it's my pleasure Jeff our second panelist and guest is Dr Alex spiropoulos Alex is a professor of medicine at the Zucker School of Medicine which is at Hofstra northwell he's also the system director of anticoagulation and the clinical thrombosis service at northwell Health Alex thanks for joining us delighted to be here Jeff and our third panelist and guideline author is Dr Bill dagger bill is a cardiovascular pharmacist he's an AC Forum board member and he's at the University of California Davis Medical Center Bill thanks for being with us today it's a pleasure now we have over 1800 people registered for this webinar which is just a testament to how important these guidelines are for everyone's daily clinical practice so I'm going to turn things over to Jim who's going to start us off with a an introduction to part of what the guidelines have to talk about in the perioperative space the objectives that we have is to really review management of anti-townbotic Agents talk about some of the important changes and discuss the implications of how these guidelines are affecting our everyday practice so Jim let me turn things over to you yeah foreign Jeff uh make sure that I can everyone can see these slides and first of all uh good morning uh good afternoon everybody uh once again it's my uh pleasure and privilege to represent uh the group of colleagues that you see here alongside Dr sparopoulos uh and Dr Dagger uh who are the panel that helped formulate these perhaps long overdue guidelines on the perioperative management of antithrombotic uh therapy these are my disclosures for your consideration foreign s were developed uh last time in 2012 and since then there's as you know been considerable changes uh new evidence in how we manage patients who are receiving an anticoagulant or an anti-platelet drug and require an elective surgery so going from 11 we went to 43 Pico questions and 4 44 guideline statements focusing in four key areas those patients receiving a vitamin K antagonist chiefly Warfarin the use of bridging therapy among those patients taking a vitamin K antagonist those patients receiving a direct oral anticoagulant or doloc and finally those patients receiving an antiplatelet drug whether a single agent like aspirin or dual antiplittle therapy without comprising aspirin and a p2y12 inhibitor typically but this is more than just a guideline a set of recommendations as Jeff was alluding to this is an area that involves a wide array of healthcare professionals and everyday practice so we felt it very important to stress the how to part of managing patients how to assess perioperative thromboembolism and bleeding how to interrupt and resume vka doax and anti-platelet drugs and how to bridge with low molecular with Heparin so evidence guidelines paired with guidance and how to this is an overview of the guideline development process I won't go through this in detail but you will see that we followed a stepwise and rigorous approach in terms of oversight selection of panel members and disclosures of potential conflicts of interest that would affect their ability to contribute to recommendations selection of Pico questions data sources based both on direct evidence that is evidence that is directly linked to a Pico and indirect evidence where it's not directly linked to a Pico but related and important the the guideline framework the evidence synthesis and importantly how we actually came up with the recommendations at the end you'll see here so let's start off and just jump right in and I I for one as and the others want to try to keep this as conversational as possible that we can with an audience of over a thousand people and we will be checking as Jeff said our chat and have ample time for Q a but this is meant to be very practical so let's start with a case of a 75 year old female with atrial fibrillation who is receiving a dullac it could be a pixaban it could be riveroxaban and has a number of comorbidities that lead her to have a chat score of six and she is scheduled to have hip replacement surgery next Friday uh the uh 16th of September uh with spinal anesthesia so a number of questions that you uh and as a pharmacist or a nurse practitioner or a clinician might get is from the surgeon and the anesthesiologist when do I interrupt the apixaban or riveroxaban is it two days three days or five days and I know there's some tension uh with the guidelines that we propose and those of other medical groups for example the American Society of regional anesthesia and we can discuss that in the Q a if I do interrupt River Rock Savannah or a pixabang for three or five days do I need to bridge with low molecular Heparin and finally as we sometimes do in patients on Warfarin do I need to check the anticoagulant or in this case the dolac level before the surgery on Thursday now the guidelines try to address these questions uh and I will I won't go through the actual studies that sort of provide the background I I invite you to look at our published report that provides more detailed background for the justification of each guideline statement so in patients who are receiving a pixaban let's say require an elective surgery we suggest stopping the epixy band one to two days before the surgery procedure versus continuation so this encompasses a broad range of patients including the patient that we discussed just now who's having what we consider a high bleeding or a surgery so as Alex will sit we'll discuss later each of these clinical scenarios is anchored on an assessment of thrombolic and bleeding risk and in this case bleeding risk dictates how long to interrupt the anticoagulant therapy and and you'll see that each guideline actually has a practical pairing so what we refer to as a guideline implementation consideration so it we in this case we talk about interrupting a pixaband one day before a low moderate lead risk procedure two days before a high bleed risk procedure such as this you'll see also this is a conditional recommendation because these guidelines have a very very high standard for developing a strong recommendation and it is based on observational studies non-randomized trial studies that we consider high quality but nonetheless are not randomized trials and therefore this is a conditional recommendation and if we were considering this patient being on riveroxaban it's essentially the same recommendation indeed we have separate recommendations for each of the four Deluxe I'm not going to repeat what I've just said for pixabad but this would be the case for rivaroxaban and also we have guidelines for patients on edoxaban and the bigotran do I need to bridge with low molecular and heparin our guideline here says we says just against perioperative Heparin bridging again this is a conditional recommendation based on low certainty of evidence where it reflects observational data assessing the use of bridging perioperatively in a non-randomized study setting and once again the the guideline information implementation consideration forgive me provides a rationale for that why we do not advise in favor of perioperative bridging for patients who are receiving a doc or direct oral anticoagulant once again I urge you to look a little bit more between the lines uh in the in the text to provide that sort of rationale for this recommendation and then finally we suggest in patients who have no AC Interruption against routine DOA coagulation function testing to guide perioperative dolac management once again this is a conditional recommendation and there's a bit more of a lengthy explanation or consideration that we offer to practice inclinations as to the rationale and we also provide some caveats in terms of when we might consider doing do ACT Testing this is meant to be a practical uh guideline and guidance document so we are not over circling these questions that come up very frequently in everyday clinical practice this figure uh summarizes the entire approach that is used for the perioperative management of patients who are receiving a Doak and we hope this is one of the key takeaways that people remember that they can maybe uh print and put in their Clinic because it summarizes the approach for doe act management and we urge you to just focus on some key uh slides or figures that encapsulate all of this evidence so we said there were four key areas we're taught we we mentioned doax uh Warfarin bridging and anti-platelets so I'm going to do the bookends and talk about the anti-platelets while Dr spropolis will deal with the vkas and bridging and here's another kind of typical case a very simple straightforward case if you may consider it a woman a man sorry who had an ischemic stroke three years ago likely another Tia we know those can be sometimes difficult to categorize and as having a bilateral inguinal hernia repair that some of us would consider low moderate bleeding risk and what do we do with the aspirin perioperatively well we all know there's been new research in the perioperative management of patients who are receiving anti-platelet therapy and here are recommendations are is that in patients receiving ASA who are having an elective non-cardiac surgery we suggest aspirin continuation over into corruption this is a conditional recommendation with moderate certainty of evidence and with the caveat that it can be modified based on the bleeding risk of the patient so for example if this patient was having a high blood surgery maybe we would be interrupting uh the warfarin depending on how that surgery is categorized so there is some flexibility built in here to allow for individual circumstances particularly given the wider wet array of surgeries and then the corollary that's why we have 29a 29b is that if we do interrupt we suggest stopping aspirin uh earlier than uh than uh the seven to ten days before the surgery this figure summarizes the perioperative anti-platelet management and of course we also deal with patients having coronary bypass surgery and importantly those patients undergo who are receiving dual anti-platelet therapy that and once again we can discuss this during the chat so with that I'm going to pass the Baton over to my colleague Dr Alex spiropoulos we'll be talking about vitamin K antagonists and heparin bridging thank you Jim and I'm going to try to share my screen um seems that maybe we have to unshare so I can share according to what I have here is there ah thank you yeah so uh as uh Jim alluded to I will be discussing uh the management of uh patients who are on vka as well as as well as the potential need for for Heparin bridging and Alex if you want to put your video video on that would be great sure thank you all right so uh the changes in the 2022 just guidelines will be profound for the practitioner who's managing patients on um on Warfarin and perioperative situations and um I I did think it important to provide some of the background data because indeed these changes will have I think important uh clinical implications and perioperative settings for some reason my slides are not advancing let's see okay so in any perioperative management of antith thrombotic therapy I think it's important to assess patient and surgical risk factors for bleeding and thrombosis and appropriately risk stratify each of these factors now back in 2008 we developed a three-tier thrombumbolic wrist stratification scheme with respect to risk of thrombosis when discontinuing vka therapy and paraprocedural situations dividing patients into low moderate and to high risk and these are the three usual patient populations on on chronic Coral anticoagulant therapies that we would see in our clinical practice based on atrial fibrillation mechanical heart valve and venous thrombolic indications and as Jim Ducatis alluded to even though this uh scheme has not been validated uh I think we have found over the last 14 years or so that it's extremely a useful conceptual model for clinicians and indeed anchors are um our guidelines with respect to how uh we risk stratified patients on paraprocedural settings now a few years later we also developed a three-tiered surgical or procedural related bleed risk scheme dividing procedures into minimal low moderate or high lead risk situations and again this has not been validated but again provides a very helpful conceptual model of what to do with anticoagulants in parapresidual situations so in essence I think we should all maybe keep in mind this slide which is important um when you have a patient in your clinic uh who's on chronic oral anti from therapy and requires an elective surgery you should be aware uh and place patient into one of these uh nine potential categories including a three-tiered uh bleeding risk scheme and a three-tier thrombolic risk scheme now importantly it's the uh procedural bleeding risk that determines if oral anticoagulant therapy is discontinued during uh the procedure and if it is discontinued when is the optimal time to discontinue it where it is the thrombolic risk again of patience on chronic uh vitamin can antagonist therapy especially at moderate and high risk that determines um if uh Heparin bridging therapy uh would provide benefits so I think this is an important conceptual framework so there are two key questions regarding management of patients on chronic uh Warfarin number one should the warfarin therapy be discontinued but I think equally as important if uh bka therapy needs this continuation should the patient require perioperative bridging therapy with either unfractioned Heparin or uh more usually alone like what happened and lastly if this is the case how to bridge with heparin now let's tackle this first question I I think what we've seen in the last decade or so is that our Cardiology colleagues have conducted high-level randomized controlled trials uh usually in uh cardiac procedural settings such as pacemaker or defibrillator placement also catheter catheter ablation in patients atrial fibrillations that clearly show benefits of a strategy of continuing Warfarin versus discontinuing Warfarin and initiating Heparin bridging perioperatively again the latter approach leads to an increase in bleeding events in procedural situations and paradoxically at least and and one random moist trial also leads to um an increase of per procedural thrombolic events so this forms the basis of I think one of the more important strong recommendations there are two in the entire guideline group namely in patients receiving vka and require pacemaker or ICD implantation we give a strong recommendation to recommend continuing bka therapy as opposed to vka Interruption and heparin bridging again a strong recommendation based on moderate certainty of evidence and of course there is a guideline implementation consideration that you see here that is connected to the statement the the other statements I think are important and again these are based on Lower quality evidence from either um smaller randomized trials or observational studies and this really have not changed much since the 2008 iteration of these uh perioperative test guidelines that in patients who require dental procedures dermatologic procedure or ophthalmologic procedures such as cataract surgery the suggestion is is that one should continue vka over a vka Interruption again these are all conditional recommendations based on either low or very low certainty of the evidence we also have added one further recommendation in patients undergoing colonoscopy with anticipated polypectomy is that if patients are receiving BK therapy we suggest against Heparin bridging During the period of vka interruption but I think it's the more important of the two questions and this is a question that's been front and center in many paraprocedurals uh uh thrombosis practitioners for probably the last 25 30 years or so is the second one if vka needs to be discontinued because of procedural bleed risk should the patient have perioperative bridging therapy with Heparin and if so how to bridge with set with heparin but the bridging therapy um or the perceived need for for bridging therapy is really driven by thrombobolic risk so that uh in high thromoombolic risk patients and I've already introduced the uh purported thrombobout with stratification scheme that we've used the need to um to prevent thrombolism will be the dominance management strategy irrespective of procedural bleed risk and thus in theory and aggressive strategies such as bridging therapy is Justified conversely in low thrombocous patients the need to prevent thrombumbolism is less dominant the strategies to avoid bleeding are Justified and in moderate thrombolic with patients a single strategy is not dominant and management has has to be individualized but the key clinical question that we have not answered until very recently is simply do we need to bridge at all uh and I think this is the the the most important uh uh clinical question because again bridging involves a very complex Paradigm of discontinuing Warfarin and initiating bridging therapy uh uh re-initiating Warfare and discontinuing therapy so data in the last decade or so from large meta-analyzes as well as large cohort trials in the three patient populations that I've introduced mechanical heart valve atrial fibrillation BT populations on chronic Warfarin for the first time um had no bridging comparatus when compared to bridging strategies and these studies uh interesting enough uh did not show any evidence of benefit of bridging therapy with either no evidence of the reduction in perioperative thrombolic events and paradoxically some studies showing an increase in perioperative thrombolic events and all of them uniformly shown in anywhere from about a three to nearly five folks increased risk of major bleeding so it was against this background and here we have the background 30-day event rates and no bridging arms uh and our Kill from a bog event rate of about 0.5 to 1 and major bleeding rates of about one percent so it's against this background we designed the rich trial um and we see here that two hypotheses these were an atrial fibrillation patients um who had at least one stroke respecter so our hypothesis for the trial was that foregone bridging anticoagulation would be non-inferior to bridging this loan like what happened for the prevention of perioperative arterial thrombolism and foregone bridging anticoagulation as with I think most of what would find evident would be superior to bridging with respect to Major bleeding now both of these hypotheses had to have been met for the bridge trial to be successful and the other interesting thing about the rich trial is that virgin was so ingrained uh in vascular surgeons cardiologists internists and others mind that that the no bridging arm was the experimental arm in the bridge draw I think something quite interesting this is the rich trial design again large trial over 1800 patients with atrial fibrillation and I won't go through the details but suffice to say that the way we designed a bridge was to maximize any punitive benefits of bridging therapy and minimize any potential harms of bridging therapy so their patients were randomized before the procedure um Warfarin would stop five days before the procedure studied drug either a Delta print or Placebo injections this was a placebo-controlled trial we'll start at day minus three discontinued day minus one and then depending on procedural bleed risk the study drug was restarted either within 24 about 24 hours for low leapis procedures and 48 to 72 hours for high feverous procedures in addition to reinitiation of Warframe and I think any of you know the results of the rich trial numerically almost identical numbers of retail thrombolic events in the Virginia no bridging arm clearly meeting the non-feriority criteria of the trial and probably not surprisingly and over two and a half-fold increased risk of major bleeding favoring the no bridging Army and lastly in some of the secondary analysis we see an increase in the number of myocardial infarction events and when we look at why that may be so what we see here is the median time to Major bleeding event after the procedure was about seven days was the median time to a thrombolic event was 19 days suggesting that bridging therapy may have placed a patient increased risk of major bleeding necessitating discontinuation of all antithrombotics and then putting the patient at risk for Downstream thrombol events now the other major trial that was published just last year was the periop2 trial uh there were a lot of limitations for this trial and I won't discuss in detail but this is another large placebo-controlled trial and the importance of the periopter trials that it included a fairly large amount of mechanical heart valve patients in a placebo-controlled trial of bridging therapy and this trial found a very similar results of the rich trial there were no advantages of bridging therapy whether you looked at the whole study population the atrial fibrillation subgroup or the mechanical heart valve subgroup of the perioctal trial and again about 50 percent of valve patients included valves in the mitral position based on these two trials and others evidence this was our second strong recommendation in the guidelines in patients receiving bka therapy who required to Interruption but we recommended um against pepper and imaging this is a strong recommendation based on moderate certainty of evidence and underneath you see some of the key guideline implementation considerations that in selected patients consider that high risk for thrombundalism and again I refer you back to the three-tier thermal about risk scheme that I discussed earlier um these would be the patients in whom Heparin virgin would be suggested and based on either direct data from the period to trial or indirect data uh from other studies in the setting of VTE we also suggested against Heparin bridging both for mechanical heart valve patients as well as patients with BTE indications and again with similar guidelines and implementation considerations that those patients at high risk based on the thrombin bald risking we suggested the use of bridging therapy and really this would be the guideline statement in which this was again defined so in patients receiving BK therapy were classified as high risk of thrombolism and again I referred you to that three-tier thrombot risk scheme that I described earlier and who do require VK Interruption because of the procedural bleed risk um again we would then suggest that when bridging over a bridging strategy the other aspect of our guideline document and something that Jim Duchess already alluded to is the how-to um of how we manage perioperative vka and moment preference bridging if it's needed so here in figure one um again we I think developed a very nice schema on what to do with respect to uh Warfarin Interruption of lack thereof and minimal bleed risk procedures and then a low moderate High leaders procedures how to interrupt Warfarin how to initiate pre-operative loan like what happened bridging and how to re-initiate warfarin post procedurally post-operably as well as reinitiating um bridging in the post-operative situation again these reflect guideline statements that are all conditional recommendations based on very low to low certainty of the evidence again they're online clinical decision support tools that are referenced in the um in the document uh and to conclude then I hope to have shown you some very major changes in the 2022 uh test guidelines that uh we all know and we think will impact clinical practice and in essence simplify uh the perioperative approach of how we manage Warfarin uh in uh in various surgical situations so is Interruption of bkas indicated we have high quality randomized control trial evidence that for many many cardiac procedures including pacemaker placement and defibrillator placement uh that uh strategy of continuation of War for the superior to Interruption of Warfarin and heparin bridging but I think the most fundamental question that has only been answered recently is is heparate bridging actually even necessary with Warfarin So based on the uh evidence that I've showed you and based on the results of Legacy now uh to publish placebo-controlled trials uh again uh we give strong recommendations not uh to bridge uh patients with atrial fibrillation indications unless uh they're at high pharmabotic risk and a suggestion not to do the same in patients with mechanical heart valve as well as a VTE indications unless again they're classified as high thrombotic risk based on the problem about risky that I showed you uh previously and of course lastly the how to manage of Warfarin and bridging in elective procedures has been validated both in the rich trial and in other trials as well so with this I think we're on time and we can go ahead and open the discussion we have plenty of time uh for questions from our audience well Alex thanks so much for for that summary that was great and Jim beforehand I want to invite uh Jim and Bill uh to join me back we are getting just a ton of great questions from the audience some were emailed in ahead of time and many are coming in now if you have questions please put them in that q a box down at the bottom of the screen and Alex if you're able to stop sharing that'll sort of bring our our cameras up I'm going to start with a question actually for Jim I know he's uh pulling his camera out right now Jim you alluded to this when you gave your section about sort of this discrepancy between the accp guidelines and the ask for guidelines for how long we should be holding our directoral and equivalence especially for patients who are going to get a spinal anesthesia type procedure and I'm wondering if you could briefly help us understand maybe where that discrepancy is coming from the the evidence that's driving it but then perhaps more practically how how as clinicians are we supposed to use this in day-to-day practice you know um should we just go ahead with the longer hold because then everyone agrees or is that a dangerous approach how do you operationalize this right now thank you Jeff that's a very important question and I think each of us gets gets asked this uh several times in my case every week and I first want to point out that both uh groups of clinicians anesthesiologists and non-anesiologists are aligned in two ways number one we want to we want to approach that is the safest possible for the patient and in this case this involves ensuring that there is minimal to no anticoagulant effect of the time of surgery so as to allow neuroxyl procedure to safely uh proceed the second is that we want to have an interruption interval so that we have approximately five elimination half-lives from the time of interruption to the time of the surgery and in that regard both the accp and Azure approaches are very consistent uh if you look at the interruption intervals that are recommended by chest iccp for naraxial which is two days off prior to the procedure this corresponds to about 60 to 68 hours interval which in turn corresponds to five elimination half-lives for most of the dialects I'm excluding the bigotran in patients with renal insufficiency that's a different situation but not widely used so we're very consistent in terms of the premise of safety and the premise of uh elimination half-lives where we might differ perhaps is how we came to our conclusion so our conclusions from the accp chest are anchored mainly on clinical data and this is primarily from the pause study from other prospective studies and from retrospective studies of the large AF trials and whereas in azra they also incorporate a lot of PKA pharmacokinetic studies done in healthy volunteers for example so you know there they have a broader array of evidence where they investigated doses frankly that are are just too high so I just want to leave us with the with that message that we're we're consistent and forgive if you're taking a long time with this answer but I think it's an important one so at the end of the day how do we reconcile uh if if there are people and as this happens in my institution that are very aligned with the Azure recommendations we don't sort of try to twist their elbows in a manner of speaking because the differences are are subtle two days versus three days the approach that we've always taken with all anticoagulants whether it's Heparin low molecular Heparin Warfarin Etc is to have that Interruption period that will allow safe surgery but not to extend it beyond that so we could say three days somebody could say five others could say a week and it it starts a bit of a slippery slope uh so I I I welcome others comments but uh again my apologies for the long response very important question and I think okay okay go ahead so just if you look at the guidelines at the very beginning we do discuss the fact that there are outliers out there that may have poor elimination because of drug interactions or genetic profiling and such and obviously many of these could have been excluded from some of the trials could just keep that in mind when you're making these decisions that there are those outliers they're not the common situation but you should pay attention to that so that you don't end up with something you don't want that's great Alex I want to turn to you and you know you really highlighted the importance of that table that sort of outlines the the risk of thromboembolism and you know I can remember back to my days in training that being sort of such a central table you know I'm thinking even back to the 2008 version of these guidelines you guys all did but they've updated and they've changed over time and I wanted to ask you about a couple of them that are in this most recent version you know in that high risk category you now have a term there called anti phospholipid antibodies and you know this is something I think all of us as clinicians are seeing a lot what did you guys mean when you put that in there is that somebody with a formal diagnosis of apls is that somebody who's had a prior clot and has Labs is that somebody who just has a positive lab that was checked and what does that practically mean how do we apply that piece of it I think it's a relevant question Jeff and really when we look at the the high risk criteria what we really mean are patients with severe thrombophilic States right or severe acquired hypercrackable state so it really for antiphospholipid antibiotic syndrome it's truly the the patient that meets the clinical definition of the syndrome meaning that they have the persistent elevations of the various antiphospholipid antibodies as defined by societies and they've had a clinical event so they've already declared themselves as a high risk patient this does not include patients who have serologically positive Auto antibodies that and no clinical events or or they're still they don't have evidence of persistence right um Auto antibodies as well and this for example could happen in covet we've seen that a lot of times that these can cause us so we really mean a good good examples of homeless viscosity right uh for the you know uh uh for a factor five light and uh or or double heterozygosity or antiphospholipid syndrome so this is really the spirit of what we mean by high risk in the BT situation you know that's really helpful grounding it in the person who's had a thrombotic event and then when you do go to explore why that might push them into this anti-phospholipid antibody sort of group there does the same apply to the other group that I see listed which is associated with vena cava filter you know we see a lot of people who have filters put in for a whole bunch of reasons is the filter the problem or is it somebody who's had a clot with a filter that's really that high risk patient yeah you know Jeff that that's a very subtle uh a very important point so again when these first iteration of these thrombogo stratification we were younger men in those times I remember that well you know the data there uh really was Data based on the old permanent IVC filters um and the risks of IBC filter thrombosis especially in the cancer population now of course the filter of the the field of filter implantation has really remarkably changed in the last 10 years or so so now we're having um non-permanent uh temporary filters placed in multiple situations so the spirit of that again um much as I said before is that pace has already declared themselves as high risk because they had a thrombotic event around placement of the filter or why a filter was placed and especially especially uh that that really refers to the patients uh and and oncologic situations with active cancer or recent cancer or other very high risk phenotypes such as for example antiphospholipid syndrome Etc so that's the spirit of of where that comes from so so what I'm hearing you say is that just because somebody has a filter doesn't automatically mean they're high risk and need bridging you got to understand more of the clinical picture of why that's filters in and what else is going on exactly great hey Bill I want to turn to you you know many of us who who work in anticoagulation think of these guidelines as being about anticoagulation but we forget that there's a whole area of anti-platelet therapy that that is addressed here um and and one of the questions that I know as a cardiologist I often get answered is well if I have to stop my p2y12 inhibitor do I need to bridge that patient with kangalore and the guidelines here were pretty clear that that should not be a routine practice but of course people always want to know well when is it appropriate and I'm wondering from your perspective what would be the kind of situation where you would say maybe we do need to go ahead and use a short-term agent like kangarelor sort of to bridge while that p2y12 inhibitor is is coming off before a surgical procedure yeah so actually I have a fair amount of experience and we actually published a paper on this using entire Five band and uh some practice a lot of times we have to think about how the stent risk is the cardiologist obviously as you know do not want uh instant thrombosis occurring we're doing complex PCI procedures now and so when you have these fresh stints these are not stints that were say placed more than three months ago that seems to be one of my clinical cutouts but it's also where is the stamp located the numbers stance and the nature of the stents so you have to get a little bit more granular in making these decisions for these patients and uh it's going to be a little bit more case-by-case basis but there are those patients that are super high risk shortly after stint placement and there's a procedure that now needs to be undertaken and it's going to be delayed for a certain period of time then you might consider using a parental anti-platelet agent for bridging those patients because of your concern for the stint but obviously people who have had stints that are chronic they've been there for a long period of time there really isn't probably a need to do this bridging approach with net parental anti-platelet agent yeah that's helpful you know I often get this question and my first response is do we really need to do the surgery or could we put it off long enough to just hold the anti-platelet but when we can't then I'm thinking about those left main stents those prox lad stents right the ones that are really high risk and and as you said it's very selective when you might use a short-term agent that's that's helpful to have that in the guidelines yeah just so you can maybe weigh in Jeff I mean to me if it's a very distal stint I'm not as concerned about it per se in practice although the cardiologists should probably weigh in in this decision process if it's not on a Cardiology related service yeah I think that that's that's really important that multi-disciplinary discussion is is critical Jim I want to turn back to you you know we've gotten a lot of questions from the audience here about how to manage doax in that perioperative space and and a lot of them really get to the question about renal function and we use renal function to help us dose dox especially in afib right we think about our dose suggestions um does that apply in the periop space it seems like from the pause study it really didn't except for the bigotran and can you help us understand why and you know as we're going out to explain to others why renal function shouldn't play a role in how long we're holding it uh thank you Jeff that's a great question and I think we're learning a lot in general terms about doax and impaired renal function outside of the perioperative setting uh especially with the 10A Inhibitors um in the pause trial uh this did not really inform the management apart from a small minority of patients who are on the bigotran and had impaired renal function um so we felt that the degree of renal function was not uh so great that it would change a general Paradigm in terms of interruption and resumption in support of this we did not find in subsequent analyzes that renal function was a predictor of perioperative bleeding or thromboembolism for that matter although the concern would be more about bleeding because you know if you've got Imperial function maybe you need to interrupt longer so patients don't bleed but we did not find that so I think um as we learn more about renal function and relax in general I think the message is that maybe it's not as important especially when the clearance is only between 25 to 33 percent for the most commonly used oax got it got it yeah I like to interject this is an actual question that we had a lot of discussion about we really took a lot of careful time and efforts to think about it the pause really depicts not really a need the levels are described in pause and such but there are certain severe renal impairment populations and also when you add in a drug interaction on top of the renal failure that could become a significant factor where you might start actually with a higher level than you think in the duration of hold may not be sufficient but these are outlier populations but we still may want to deal with them but the general average person in such it seemsly and for soup especially surgeries are not as high risk for bleeding it would hold up with what we're trying to say for the general approach but there are outlines out there we still all we should consider yeah it's it's uh one of the phrases I think we often hear is guidelines are the place to start but they're by no means the only way to practice and so it's a good starting point and then think about what your individual patient needs that's helpful they're not the places to end they're a good place to start but not the place to end that's a great way to put it that's a great way to put it hey Alex I want to turn to you one of the I think personally one of the biggest changes in these guidelines is the approach to Mechanical Valves and there have been a lot of questions from our audience about that um and I'm wondering if you could walk us through a little bit you know we see the recommendation for those low risk aortic valve patients that maybe don't need bridging anymore we've now got some evidence that's coming what's it going to take for us to actually change practice I think for so many clinicians mechanical valve equals bridging and they just don't even think about it how are we going to actually take these guidelines and start to shift that practice a bit what are your thoughts in that space well if you believe um the literature will take about seven years before from the publication of guidelines to implementation clinical practice as I hope I had introduced our audience these guidelines are protect potentially practice changing because not only for the mechanical heart valve population but in my view for the atrial fibrillation population which is the largest chunk of patients on chronic Warfarin these guidelines I think will have tremendous implications so when you look at the actual numbers only about 20 percent of patients with AF or mechanical heart valve indications truly are in the high risk category so what we're saying is is these are the patients you know that's the low-hanging fruit so if you truly have a high risk AF patient for example very high chance bass course or more importantly a patient who's had a periprocedural stroke or thrombotic event right with atrial fibrillation um those or mechanical heart valve that's an older caged ball type valve you know or of course uh a patient with a valve in any position who's who's succumb to a thrombotic event these are all the patient phenotypes that we truly label as as high risk and if you choose to bridge that patient that's on you and that's acceptable you know what we really are what we mean is number one not all patients with atrial fibrillation need to be bridged and I have to tell you uh in my view based on my reading of the literature in the last decade there was a strong bias in the Cardiology Community to Bridge I remember the Acca guy lines in 2014 recommended bridging therapy okay based on the exact same evidence that we had in the 2012 chess guidelines where we suggested that there would be patient groups that would not benefit from bridging therapy and as I mentioned the way the bridge trial was set up is that the experimental group was the no bridging group this is how much bridging was ingrained right in the medical community so the first thing I want to say is for the vast majority of patients at moderate risk I think what these guidelines are telling us over 50 percent of the populations you don't need to bridge period okay and these include um aortic valve patients or even some of the newer mitral valve places for example Onyx valves is a good example so unless if you have a modern low profile valve you're a young patient you have no previous history of thrombotic event you don't have any of the other cardiovascular risk factors these indeed would be the paid I just saw a patient actually last week could fit that Pro profile and I did not recommend Richie therapy for that patient these are the patients that we're talking about that don't need to be routinely bridged and I think that's the important message is is really look at the moderate risk population first right make sure you have protocols and guidelines that now with uh with this iteration of the chest guideline you say these patients don't need bridging and then for the patients in the high risk um you know high risk conditions and I think you should look at them based on a case-by-case approach what it means is that you shouldn't blanket bridging therapy for all mechanical heart valve patients yeah I think that's helpful and Bill I want to turn to you because several people have asked questions really but how do we get this into practice and and what can the anticoagulation Clinic Pharmacist or nurse or maybe the the pharmacist who's rounding on the service how can they influence the way these guidelines and recommendations are being applied and I'm wondering if you have thoughts or recommendations how do we get the Physicians to sign off on this evidence-based guideline practice what would you recommend to folks well that's the irony is that actually now that this has come out I'm rewriting all our policies for bridging and for our institution and we'll present it according to to multi-disciplinary community and get all the key physician groups to sign off on it once you get all the key players in your institution on board and they realize the risk benefit then you can actually institutionalize this based on the evidence but also give flexibility to any concerns that the unique clinical practice practice groups may bring up adapt them to your institution accordingly but it meets good communication with all the parties involved not only the clinic and what they make recommendations for but also what happens in the hospital and also some of the stuff we deal with about restarting anticoagulation after the procedures and how we approach it so you look at the big picture and you look at the optimal way but now we have a great evidence-based document as a basis to form our policies and then change your order sets and everything accordingly to fit your policy and how you can approach it yeah so so policy change and just you know taking ownership I think is a key and having that conversation both before the patient ever shows up and when you have those patients there and in that repetition's key Jim I want to turn to you we're getting lots of questions about anti-platelet therapy and this was obviously a big one in in the guidelines here you know there's been a general reduction in the use of aspirin I think overall we're seeing less primary prevention aspirin less combination therapy aspirin but aspirin's still a really common antiplatelet and you know what would be a couple of your take-home messages about how we should be approaching aspirin therapy in the periopic space yeah thank you Jeff let me first talk briefly about just patients on single antiplatelet therapy and this is typically ASA 81 milligrams and the accp made a recommendation in patients undergoing non-cardiac surgery to continue uh ASA perioperatively which may have raised some eyebrows I can tell you this is one of the few domains where there was not complete consensus among the panelists I think reflecting some of the um and to you about how to interpret the evidence I mean nonetheless the the recommendations were based on mainly on the pep and the Poise II trials both Landmark important trials but it also looks at how we interpreted the evidence for example in the Poise 2 trial there were concerns that a high proportion of patients were using NSAIDs and this may have attenuated some of the the benefits of continuing anti-platelet therapy moreover in that trial if you look at the ASA continuation stratum there is no significant difference in major bleeding so uh having said that we do have a caveat that and you know we do want to consider interrupting in patients at high risk for bleeding so you know I welcome readers to look at that part and uh interpret it as they as they see fit the other big area the two other big areas were cardiac surgery which um we essentially had similar recommendations as previously and the new area I think as Bill had alluded to involve patients who were receiving uh dual anti-plated therapy and and here this is an area that we urgently need more research and our our recommendation which was conditional that to continue the ASA aligning with the recommendation and non-cardiac surgery and bypass surgery for that matter but interrupting the p2y12 inhibitor typically five to seven days is based on you know rather weak observational data and as Bill alluded to can be modified the vet depending on individual patient circumstances number of stance whether it's a critical lesion and so on so uh yes we made a lot of progress but there's still a lot of room for improvement to inform best best practices five to seven days so everybody's aware like when you look at Clopidogrel or alpraza grill the effects are gone within six to eight hours after the dose and all you're waiting for that five to seven day period is for platelets to fully regain their complete effectiveness at close to 100 percent but you know if you go three days you've gain 50 with those agents so keep that in mind that the drug is no longer there in impacting the playlist but you are getting higher amounts of platelets and you may have some window of doing the surgery earlier if you're not concerned about having full return of platelet function tycogler is a little different but this I'll just add that caveat with that five to seven day period awesome that's that's really helpful I want to close with a couple really brief but very practical questions that have come in and Jim I'll pose the first one to you you know when we look at that protocol for stopping the doax pre-op that really came from the pause study um I want to use the case how do we figure out the exact time to tell a patient to stop their pills so you used a case of the patient who's having surgery on Friday let's let's call it 10 a.m and let's say we decide to stop her a pixaband two days beforehand a 48 hour hold practically speaking what does that mean when does she take a dose when does she not take a dose can you help us translate that yes and I think as we all know in this space Simplicity is of Paramount importance so we've tried to keep the wording simple that's why we say two days off so that means the last dose is on Tuesday you're off Wednesday you're off Thursday of course you're off the day of surgery and um I can't emphasize the importance of that enough alongside communication we can do that better now in an EMR World between different Specialties and colleagues and and Alex to you the same kind of question if I'm doing a Warfarin patient and I'm going to bridge them with a low molecular weight Heparin you know again surgeries on Friday when do they get that low molecuade Heparin and when do I stop it so they can go and have have surgery do they take that long liquid Heparin right up until Thursday but beforehand how do you practically operationalize that so that what we've seen in the RCT data is that a full 24-hour stop uh would be optimal of course we do have conditions that you can give half dose of the daily dose should you choose for flexibility but but preferably um you hold that role like what happened pre-procedures for a full 24 hours there there is some indirect data from 10A level uh vennae levels that you have accumulated 10A levels if you stop sooner than those 24 hours and this is what I mean where I think the bridge trial really validated that kind of of uh of uh Paradigm because we saw in the no bridging arm a very low major bleed rate using this approach you know just one thing real quickly to add into that though is that you know these are elective surgeries we're talking about and there's also a lot of data about giving some sort of anticoagulant prior to elective surgery being done mostly in Europe but also keep that in mind in these high-risk patients there's also that option not as often practiced in the United States as much as other places in the world but those are other considerations too unless Alex gym you want to comment on that yeah I think the key is is that's really not based on any high quality evidence so I think that the key part of our recommendation is that was really based on on high quality evidence from randomized trials so I'm aware of multiple approaches but I think the the key message from ours is that we we gave our recommendations based on the best available evidence to date now that evidence can change and of course it will change but this is a synthesis of what we've seen in with the best available evidence perfect well thank you everyone this has been an amazing discussion and Liz I'll turn it over to you to close so much Jeff and thank you to all of our speakers oh my goodness doctors Jim Ducatis Alex baraboulos Bill dagger and Jeff you guys are amazing I'm so grateful this these guidelines were published last month I'm so really grateful that you were able to pull this together and share your expertise with our members as Jeff said we had over 1800 people registered which really speaks to the need for these new guidelines updated guidelines and the impact that they're going to have as Alex as you said it's practice changing so thank you so much for sharing your expertise with us and if you enjoyed this webinar please join us for our upcoming webinars we have a great webinar in honor of PID awareness month which is September um Health disparities in pad what to know as an anticoagulation provider we have a phenomenal very special speaker Dr fakhariti who's doing amazing work in this in Mississippi with the black community trying to prevent amputations improve increase awareness of pad and improve treatment so that's you're in for a treat if you join us for that and then we also will be speaking about our brand new anticoagulation stewardship Playbook um just a bit on that we just released it a few weeks ago we did it in partnership with nqf and it has all the tips and strategies you could need to create an anticoagulation stewardship program at your institution it's available for free download both on the AC Forum website and at the nqf store so please download it and join us for those webinars also to Advanced stewardship we have a brand new ashp just accredited a brand new novel pgy2 pharmacy residency in thrombosis and hemostasis management and if any of you know how what a challenge that was to do it's really rare that they accredit new residencies so we're thrilled that it's in our field and the AC Forum will be awarding grants to institutions to launch a program so the grant is actually due tomorrow so you still have time for this round or think about it for next year and you can learn more about it on our website we have two other last things I'd like to mention we have a virtual boot camp coming up it will be broadcast live October 7th and 8th and then also available for 30 days after if you can't make those days and it's a very well received very compact very uh lots of information that you need to know so please register for that and then fingers crossed or actually I'm not crossing my fingers anymore it will be live in April um April 2023 we will be in person in San Francisco for our national conference so please join us in person there registration will open soon and lastly I'd like to thank our corporate sponsors for making this webinar program possible thank you everyone and have a great day foreign