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DOACs in the Anticoagulant Treatment Landscape

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Um i’m the hematologist up here today and i guess i’m the first to be attacked by this audience which would be fine it’s because of me and my colleagues that have switched everybody from warfarin to these agents and has led to nightmares for you guys in the management of gi bleed so i apologize it’s made it much easier for us but i understand it’s made it somewhat

More difficult and confusing on your end so the point of this or at least the point of my talk today let’s give you a little bit of introduction into the into the management of gi bleeding or at least the management of anticoagulation with these newer agents which aren’t so new anymore but and then have the obviously the perspective from a from an er physician

As well as an ability to have a little bit of a panel discussion and so think of questions that might that might stump us a little bit and we’ll be happy to entertain those so not working so far ok ok so as you can see from my first slide here and i’m gonna kind of pivot here because i can read it better on this than i can in that in that screen there despite my

Glasses is the fact that as you can see here there’s four different names here and i will tell you the an interesting idea is that a gi doctor in my institution came up to me and said so i understand you’re giving a talk about dou x what’s a dou ak does everyone in this audience know what a dou ak is as compared to one of these other names up there or acronyms

Because no because i don’t i don’t describe it as a joette or i’ve never described these drugs as dou x i always describe them as no x but as my colleagues have told me up here in this audience or in up here in this panel is that they’re no longer that new so when we’re talking about new oral anticoagulants which is the no act they don’t really it doesn’t really

Make too much sense direct oral anticoagulants we’ll talk about what the other ones might be as well so i think it’s important to focus on terminology first so from the standpoint of terminology it’s important to differentiate and i’m sure this is not news to everybody that there are anti thrombotic agents which include an type platelet agents and anticoagulants

And the antiplatelet agents are aspirins plavix and those other drugs that are out there that inhibit platelet aggregation and then the anticoagulants are all the other drugs out there that we typically as hematologists and cardiologists tend to prescribe are the warfarin heparins and the oral anticoagulants like we’re talking about today so antoine has anything

That acts to inhibit the coagulation cascade so that’s warfarin heparin low molecular weight heparin direct thrombin inhibitors and factor 10a inhibitors and we’ll talk about these so these are the two dou ak kind of classes dt is or direct thrombin inhibitors and the direct factor 10a inhibitors so those are the two classes the most common one that’s seen in

The dti or the direct thrombin is dabba gatt tran which is pradaxa not a ton of use from a hematology standpoint but a ton in the cardiology space using more pradaxa for atrial fibrillation coders the first of the novel anticoagulation to be to come out in the market and they’re also some parenteral forms for the direct thrombin inhibitor zanjeer oh max rivas in

Our gat rabanne you might be familiar with from the direct factor 10a inhibitors these don’t have iv formats at all these are the drugs that you may be more familiar with robots rivaroxaban which is xarelto apixaban which is eliquis and then these two which are typically not given too much in the united states and we’ll talk about why are the ones that are the

Direct factor 10a inhibitors and and we i promised you i’d kind of define the names a bit so don’t whack is direct oral anticoagulants t so ak is target specific oral anticoagulant od eyes or oral direct inhibitors and no acts are novel anticoagulants so these all mean the same thing so you should know at least when you’re conversing with your colleagues that if

They don’t know what a dou ak is they might know what a noack is they might know what a t sock is and they might know what an odi is regardless of what it is we’re dealing with the same thing okay so some historical perspective i think is necessary to discuss this a little bit in the pre doe ak area era so pre direct and we had heparin either parentally or sub-q

Given daily or twice daily and we had warfarin now warfarin i will tell you for years and years and years i’ve been practicing for 16 up till about when the first of these drugs came out all we did for patients on long-term anticoagulation was cumin cumin and cumin and cumin cumin and clinics anticoagulation clinics they were constantly getting their inr and pt’s

Done in the odd situation we’d get people to get at home poc type units at their house to get their inr s on their own and send it over their physician but it is a it’s a royal pain and i kept telling patients it’s just a matter of time before another drug class comes out that will allow us to give you the same safety with no monitoring so that’s the problem with

Cook with cumin and you have cumin in clinics poor follow-up but patients compliance issues and the biggest issue with cumin is that you’re either super therapeutic you have an inr of 10 or you’re subterra p to get an inr of 1 so if you’re on coumadin you have an inr of 1 you aren’t doing any good if you’re on cumin and have an inr of 10 you’re in the er with this

Gentleman over here with the gi bleed or something worse okay but the therapeutic window is so narrow with warfarin that it’s a real problem which made the introduction of these drugs so incredibly useful to the people who prescribed them so these newer agents block the procoagulant activities in the generation of the fibrin clot and i have a clot cascade i will

Spend some time looking at with you guys it’ll either directly target thrombin or directly targeting factor 10a you either do those and it stops the whole cap coagulation cascade but different targets and the huge advantage is less bleeding and this is true and this has been proven much less bleeding when compared to coumadin because despite the fact that coumadin

Is easy to reverse with vitamin k or ffp potentially most patients are either sub-therapeutic or super therapeutic and the bleeding risk is much higher so less bleeding with the oral agents much shorter half-life we’ll talk about that as well and no monitoring and now reversibility it’s contraindicated though therefore in pregnancy lactation severe liver disease and

Actually does not have an indication for a condition called antiphospholipid syndrome so the pregnant patients are on and coagulation still need to be on heparin type products patients who are nursing still need to be on heparin type products and not these direct oral anticoagulants so the coagulation cascade what nightmares are made of for the non hematologists out

There i assume right no one wants to look at this but i’m gonna point out the two things so you got the intrinsic pathway on the right the extrinsic pathway on the on the i’m sorry left it’s for extrinsic pathway on the right the extrinsic pathway leave is related to endothelial injury when there’s injury it’s it starts the cascade through factor 7 this is where the

Drug novo 7 is sometimes given by my emergency room colleagues in patients who have bleeding episodes unfortunately novo 7 doesn’t have very much activity on patients on these drugs and i’ll tell you why because if you’re giving pradaxa which is a thrombin inhibitor it’s the lowest on the cascade right you’re actually preventing thrombin from converting fibrinogen

To fibrin which is the last step of the coagulation cascade the factor 10a is a little bit upstream of that and that’s either eliquis or or xarelto and other drugs here in this particular pathway so this is where it acts it acts either at factor 10 a or at thrombin alright so the indication for dou x and y you’re seeing patients in your clinic who happened to be on

These drugs well multiple indications but vte events right dvt or pe s with or without cancer vte prevention so patients who have had a knee replacement hip replacement can be placed on these drugs for about 10 – for 10 to 21 days depending on the surgeon patients on atrial fibrillation and then there are some iv uses of these drugs in acute coronary syndromes and

In heparin induced thrombocytopenia the ones that affect you guys most i think as gi doctors are patients either being treated for dvt or pe are being prevented from r some stroke prevention for atrial fibrillation and potentially patients who are on vt prevention post orthopedic surgery okay so i’m just gonna go through a at least the ones that are most common

Talked a little bit about half-life and then we’ll turn it over to our er physician actually what try to write back up to dr. jang i believe correctly okay so data guy tran is pradaxa so this again is a direct thrombin inhibitor blocks trombe and the lowest on that count coagulation cascade half-life is somewhat longer than others in this class twelve to seventeen

Hours and the most important thing about projects that’s 80% renal e excreted so not the drug that people should potentially use in patients who have renal insufficiency of any type because the majority of it is renal a excreted like all these drugs that’s unaffected by food no monitoring’s necessary it’s indicated mostly on every indication other than prosthetic

Heart valves and it’s fixed dosing and the reversible agent is practice abide or ida ruse ism ab which dr. – i believe we’ll discuss in greater detail rivaroxaban is a rel toe so rivaroxaban is a realtor or eliquis a pac seban are probably the most common ones that are utilized now by market share so this is a factor 10 a inhibitor it inactivates circulating in clot

Bound factor 10a it’s half-life is on xarelto 12 hours and what’s different about a pact i’m sorry did i go too far yeah i’m sorry why i must’ve did twice i’m sorry so xarelto is actually lower half-life five to nine hours and it must be taken with food so this is the big difference on the factor tay 10a inhibitors this drug must be taken with a high caloric meal

If patients aren’t taking it with a high caloric meal the bioavailability of this drug is significantly reduced so it’s important to note no monitoring is necessary it’s also indicated with everything for with except for prosthetic heart valves the dosing is different with xarelto it’s twice daily for 21 days followed by daily dosing so that’s somewhat different

Than a pack and it’s dose-dependent unreal function only in the af indication and the reversal agent is index annette which also dr. too is going to discuss at great detail so the difference here with eliquis or a pac seban is the half-life’s a little bit longer it’s 12 hours it’s a twice daily drug and it has everything pretty much the same as xarelto except it

Isn’t affected by food so it doesn’t have that food requirement that’s necessary and again twice daily dosing same reversal agent as an azure alto the other two which i’m just going to spend a second about on is doxa band and then tricks a ban so in doc’s a ban is actually only useful and not really used in the united states because it requires parental anticoagulation

First and for the most part and i believe it’ll be confirmed by doctor to the er physician is that we rarely send patients with vts into the hospital anymore on parenteral therapy we typically send them home almost same day either on xarelto or eliquis and they never get that kind of preload with parental therapy and because this drug was only approved after parental

Starting of therapy of loading it’s not really used that well or in this country at all and then bentrik seban is actually only used for vte prevention in hospitalized patients again to have a drug on a hospital formulary that’s just for this indication is extremely rare and i would be very surprised to hear that any of you have heard of this drug or have used this

Drug in the past so i just wanted to follow up and on two particular items that i think really helpful to going forward for this discussion number one is how we hold doh acts for procedures and second is the definition of bleeding and what is major bleeding what is minor bleeding what is other bleeding because it’s incredibly important to understand the definition

Because of the trials that are out there and because of what we can do to reverse them if necessary so no bridge is necessary for treatment of patients with no axe okay i know a cadillac whatever way you call it these patients do not need bridging with lovenox unfractionated heparin of any type they never do you should also never ever listen to a pharmacist who

Says these need to be stopped seven days prior to procedure because it’s just like cumin that’s also not true if you knew how many patients i saw with recurrent vte s and recurrent pease because they stopped their drug for seven days it would be somewhat amazing to hear because it happens all the time but the general guidelines if you’re using pradaxa two to three

Days or two to four days depending on renal impairment you stop the drug prior to a procedure and then you restart once homeostasis has been achieved and i know we can probably go into a discussion so we get to the panel discussion as to what that means to you guys in terms of restarting on the factor ten eila drugs inhibitors whether it’s robots rivaroxaban or

A pax or pixel ban it’s two days prior to a low-risk procedure three days prior to a high-risk procedure that’s it it should never be held longer than three days for anything and when we talk about low-risk procedure we’re talking about upper endoscopy colonoscopy even with biopsies that’s the low-risk procedure high-risk procedure would be any type of invasive

Surgery of any type and then again restarting once homeostasis has been achieved and then my last slide is defining bleeding definitions so there’s three bleeding definitions in the literature when it comes to oral anticoagulants number one major bleeding clinically overt bleeding a decrease in the hemoglobin of greater or equal to two grams or the transfusion

Of at least two units of blood in that patient life-threatening bleeding sites and bleeding that contributed to someone’s death so that obviously would be major bleeding if it is the next step is cr nm clinically relevant non major bleeding so it’s bleeding but it isn’t any of the above it is associated with intervention so someone a patient needs to call you or

Call their doc they need to show up in emergency rooms you have to have face-to-face contact with that patient to satisfy this definition crm you have to has to lead to the discontinuation of the drug for one reason or another or discomfort or some effect on their adl’s and examples include gi bleeds epistaxis hematuria that kind of level of bleeding and if you

Don’t satisfy major and you don’t satisfy cr and m it falls into minor and that’s heavy menstrual bleeding cut minor injuries like that and this is a helpful to know prior to having that discussion that we’re gonna have regarding reversal whether we discontinue the drug whether we hold the drug whether we give in a reversal agent that we talked about before and i

Believe that was my last slide and looking forward to the panel discussion later thank you so much

Transcribed from video
DOACs in the Anticoagulant Treatment Landscape By HMP Education