dabigatran vs. rivaroxaban

[xiphoid2010]

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Anybody has those on their formulary yet?

Both are non-inferior to warfarin. For an inpatient setting, at $6-7/day cost to pharmacy, Pradaxa is probably cheaper than warfarin + daily INR (not sure about exact lab cost). Rivaroxaban would be cheaper than 30 mg lovenox BID post hip/knee op.

Any hospital out there going these routes? Of course, warfarin would still likely be cheaper for outpatient 1x/month INR. But we are talking inpatient acute care setting. We can bridge them over to warfarin near discharge.

I wonder when Apixaban is going to get approved.

 

[spacecowgirl]

I haven't seen the rivaroxaban vs warfarin study. I thought it was only vs enoxaparin. I also didn't think dabigatran had a VTE indication other than for a-fib yet. But it's been a couple months since I looked at the studies.

I like the idea of both of them. Can't really see the point of bridging to warfarin. Might as well start on warfarin to begin with since the $$$ labs are mostly at the beginning of therapy. Unless I'm not considering something here.

I was all worried about the lack of reversal mechanism but given the short half-lives of both of them, I'm not sure the reversibility is any more of an issue than with warf. Vit K isn't an instant reversal antidote - not even if you give 10 mg IV for everything

 

[xiphoid2010]

I haven't seen the rivaroxaban vs warfarin study. I thought it was only vs enoxaparin. I also didn't think dabigatran had a VTE indication other than for a-fib yet. But it's been a couple months since I looked at the studies.

I like the idea of both of them. Can't really see the point of bridging to warfarin. Might as well start on warfarin to begin with since the $$$ labs are mostly at the beginning of therapy. Unless I'm not considering something here.

I was all worried about the lack of reversal mechanism but given the short half-lives of both of them, I'm not sure the reversibility is any more of an issue than with warf. Vit K isn't an instant reversal antidote - not even if you give 10 mg IV for everything

Sorry needed to clarify: dabigatran in place of warfarin for a.fib, xarelto in place of lovenox for post-op VTE prophy.

Here's what I'm thinking, inpatient with a.fib, start dabigatran, d/c warfarin. When nearing discharge, restart warfarin and d/c pradaxa (or if the patient's insurance kicks ass, keep him on it).

Same for post op hip/knee surgery, surgeons right now likes to put patient on lovenox for 35 days. That's >$1000. Doing it with Xarelto cost <$300. Now, if the pt's insurance won't pay for it outpatient, can bridge him to to warfarin for a month.

I'm not too worried for the lack of reversal agent, either. If I recall correctly, dabigatran has less intracranial bleeding risk than warfarin, which is the big one to be worried about anyway. I rather have lower risk to begin with than to have a reversal agent. Also, like you said, short half life = can reverse using blood products until it wears off if absolutely an emergency.

 

[owlegrad]

During our most recent anticoag case we had a pharmacist from a local hospital say that dialysis is an option for dabigatran reversal. Makes sense but that was the first time I had heard of that. Seems like FFP would be easier, though perhaps he meant if FFP wasn't enough.

I am not familiar with Xarelto (fast review makes it seem interesting though I wonder why it has such a narrow indication?), but I am suprised that it is cheaper than generic lovenox.

 

[pharaday]

During our most recent anticoag case we had a pharmacist from a local hospital say that dialysis is an option for dabigatran reversal. Makes sense but that was the first time I had heard of that. Seems like FFP would be easier, though perhaps he meant if FFP wasn't enough.

I did read on Pharmacist's Letter that hemodialysis can be used for Pradaxa, but NOT Xarelto. They also said that activated charcoal can be used, as well as ensuring adequate diuresis. It said that red blood cells and ffp can be used, but that aPCC or recombinant factor VIIa be used only as an absolute last resort (life threatening bleeding).

 

[owlegrad]

I did read on Pharmacist's Letter that hemodialysis can be used for Pradaxa, but NOT Xarelto. They also said that activated charcoal can be used, as well as ensuring adequate diuresis. It said that red blood cells and ffp can be used, but that aPCC or recombinant factor VIIa be used only as an absolute last resort (life threatening bleeding).

We had a discussion about that some time back where I said something like that, I think it was the first time I was ever right about anything pharmacy related.

That was a good day for me. 😆

 

[Ackj]

I haven't seen the rivaroxaban vs warfarin study. I thought it was only vs enoxaparin. I also didn't think dabigatran had a VTE indication other than for a-fib yet. But it's been a couple months since I looked at the studies.

http://www.nejm.org/doi/full/10.1056/NEJMoa1009638 rivaroxaban vs warfarin.

 

[Ackj]

I am not familiar with Xarelto (fast review makes it seem interesting though I wonder why it has such a narrow indication?), but I am suprised that it is cheaper than generic lovenox.

Looks like for anticoagulants they need to do a whole big study for each individual indication. RECORD (1-4) studied riva vs enoxaparin, 1 and 2 were hip, 3 and 4 were knees. ROCKET-AF was the a-fib one I linked. There's also MAGELLAN which is for medically ill VTE prophylaxis, ATLAS for secondary MI prevention, and EINSTEIN, for VTE treatment. Not all of those are published yet.

 

[Ackj]

Sorry needed to clarify: dabigatran in place of warfarin for a.fib, xarelto in place of lovenox for post-op VTE prophy.

Here's what I'm thinking, inpatient with a.fib, start dabigatran, d/c warfarin. When nearing discharge, restart warfarin and d/c pradaxa (or if the patient's insurance kicks ass, keep him on it).

Same for post op hip/knee surgery, surgeons right now likes to put patient on lovenox for 35 days. That's >$1000. Doing it with Xarelto cost <$300. Now, if the pt's insurance won't pay for it outpatient, can bridge him to to warfarin for a month.

I'm not too worried for the lack of reversal agent, either. If I recall correctly, dabigatran has less intracranial bleeding risk than warfarin, which is the big one to be worried about anyway. I rather have lower risk to begin with than to have a reversal agent. Also, like you said, short half life = can reverse using blood products until it wears off if absolutely an emergency.

Thing I liked about Xarelto, is that every ortho surgeon likes to do stuff different, and some of their post op stuff is a little questionable (short duration, just give em ASA, etc). Xarelto specifies exactly how many days you give for hips and how many days for knees, so that gets the crazy dosing out of the way.

As for dabigatran, I know RELY said it had less intracranial bleeding, but since then many pharmacists I've talked to have given anecdotes about it seeming like there was more bleeding. I know it's just anecdotal evidence and you can't base a whole lot on it, but the fact that there are multiple institutions with the same anecdote makes you wonder if this is going to be a post-market surveillance issue.

 

[gotdrugs]

Here's what I'm thinking, inpatient with a.fib, start dabigatran, d/c warfarin. When nearing discharge, restart warfarin and d/c pradaxa (or if the patient's insurance kicks ass, keep him on it).

A hospital policy/standard that switches everyone (with afib) anticoagulation therapy back and forth?

That's not a recipe for problems.

Nope......

 

[gotdrugs]

During our most recent anticoag case we had a pharmacist from a local hospital say that dialysis is an option for dabigatran reversal. Makes sense but that was the first time I had heard of that. Seems like FFP would be easier, though perhaps he meant if FFP wasn't enough.

It is an option....but I would only do it in a life-threatening bleed.

Otherwise, good luck finding someone willing to put in the line for HD access on someone who is already bleeding (or possibly "OD'ed") on an anticoagulant. 👍

 

[All4MyDaughter]

A hospital policy/standard that switches everyone (with afib) anticoagulation therapy back and forth?

That's not a recipe for problems.

Nope......

I was thinking the same thing. I am also thinking daily INRs might still be cheaper.

 

[xiphoid2010]

A hospital policy/standard that switches everyone (with afib) anticoagulation therapy back and forth?

That's not a recipe for problems.

Nope......

of course this would be a logistic issue. Must weigh pros vs. cons.

Pro of keeping patient on warfarin:
(1) no changes, simpler logistic
(2) possibly cheaper if daily INR is dirt cheap

The cons:
(1) warfarin/INR almost always drift out of range once admitted/discharged. I love it when INR shoots up, MD orders vitK IV, fixes the INR but then you spend next 5 days trying to get back into 2-3.
(2) warfarin only has a bizillion drug interactions, increasing risk to patient.
(3) Many MDs d/c warfarin and put patient on lovenox upon admission anyway, which is more expensive than either PO drugs.

I need to check up on the INR cost. If it cost <$5-6 each, then warfarin would still cheaper.

The main issue with switching between Pradaxa & warfarin is mainly gonna be to remember switching back when near discharge. I have a feeling that MD is gonna forget and send patient out on Pradaxa, unless medrec pharmacist do a good job of catching. If missed, the problem is gonna be with patients have sucky insurance, who might become non-compliant due to the cost.

 

[Ackj]

warfarin/INR almost always drift out of range once admitted/discharged. I love it when INR shoots up, MD orders vitK IV, fixes the INR but then you spend next 5 days trying to get back into 2-3.

I sure hope you don't do this. Unless they're bleeding, have an INR > 8, or need emergent surgery, hold the dose for a day or two.

 

[Don Quichotte]

I work in an anticoag clinic on occasion...one thing that strikes me is how many patients tried dabigatran and then came back to warfarin. The reasons vary---some did not like the copay for dabigatran, some had stomach upset, some had bleeds. Those were all issues I could have imagined coming up, but the one issue patients have mentioned for either why they came back to warfarin or why they will not leave it, is that they LIKE getting their INR done and knowing they are in range. I realize this is an anecdote from my experience in the clinic, but nevertheless, I would be curious what others have found in the field.

 

[xiphoid2010]

I sure hope you don't do this. Unless they're bleeding, have an INR > 8, or need emergent surgery, hold the dose for a day or two.

I don't do this, the MDs do, the nurses override and gave meds out before I even see the order half of the time. I know the rules of when to reverse.

 

[a runner]

I work in an anticoag clinic on occasion...one thing that strikes me is how many patients tried dabigatran and then came back to warfarin. The reasons vary---some did not like the copay for dabigatran, some had stomach upset, some had bleeds. Those were all issues I could have imagined coming up, but the one issue patients have mentioned for either why they came back to warfarin or why they will not leave it, is that they LIKE getting their INR done and knowing they are in range. I realize this is an anecdote from my experience in the clinic, but nevertheless, I would be curious what others have found in the field.

I know it's all anecdotal evidence, but I'm the third person to agree with this. I did an MUE on Pradaxa use at the hospital I interned at and though it was a small sample size (~25) because I was doing the review of use before it went formulary at my hospital, there was a sizable population that had GI bleeds (4), even though RELY puts the % of GI bleeds at something like only 4-5%. One of them even required 4 units of blood. Though that one was probably exacerbated because the physicians were making stupid mistakes like using Lovenox concurrently 😕.

 

[a runner]

Anybody has those on their formulary yet?

Both are non-inferior to warfarin. For an inpatient setting, at $6-7/day cost to pharmacy, Pradaxa is probably cheaper than warfarin + daily INR (not sure about exact lab cost).

Pradaxa got put on the formulary at the hospital I interned at this summer. In fact, I was at P&T when it got approved. My clinical coordinator was against it and the cardiologists were trying to get approved for more than 6 months. Anyways, isn't Pradaxa more like $10 per pill and it's BID so ~$20/day? I definitely think there is a big cost difference especially for the patient after discharge, making compliance an issue.

 

[gotdrugs]

The main issue with switching between Pradaxa & warfarin is mainly gonna be to remember switching back when near discharge. I have a feeling that MD is gonna forget and send patient out on Pradaxa, unless medrec pharmacist do a good job of catching. If missed, the problem is gonna be with patients have sucky insurance, who might become non-compliant due to the cost.

That's one issue. And it's a big one. There are numerous incidents over the years of patients taking duplicate therapy at home due to auto-conversions while they were at the hospital.
(e.g. hospital has a statin auto-sub patient was taking atorvastatin at home, was switched to simvastatin in the hospital, was discharged with a simvastatin prescription. kept taking both their original atorvastatin prescription and new simvastatin prescription)

2nd is the timing and logistics. if someone comes in with a therapeutic INR (or supra-therapeutic INR), when are you going to start dabigatran? If you say day one, you might want to read the literature out there on switching anticoagulation therapy. (btw, which is what I was alluding to in my original post) It's not easy to find, but it's there, and it might save you some future problems down the road if you take heed to it.

If you do this, good luck to you 👍

 

[xiphoid2010]

That's one issue. And it's a big one. There are numerous incidents over the years of patients taking duplicate therapy at home due to auto-conversions while they were at the hospital.
(e.g. hospital has a statin auto-sub patient was taking atorvastatin at home, was switched to simvastatin in the hospital, was discharged with a simvastatin prescription. kept taking both their original atorvastatin prescription and new simvastatin prescription)

2nd is the timing and logistics. if someone comes in with a therapeutic INR (or supra-therapeutic INR), when are you going to start dabigatran? If you say day one, you might want to read the literature out there on switching anticoagulation therapy. (btw, which is what I was alluding to in my original post) It's not easy to find, but it's there, and it might save you some future problems down the road if you take heed to it.

If you do this, good luck to you 👍

I'm aware you wait until INR <2 to start dabigatran. But the staff do needs to be educated.

You raise some good concerns, and they are indeed valid. Im not asking for auto sub, they are not the same drug class. MDs will have to order it. During the medical team meeting next month, I'm presenting these 2 drugs, I got a feeling they will ask for it. however, it's only a matter of time that warfarin is replaced, maybe not today, not tomorrow but it is not too far off now.

 

[Ackj]

however, it's only a matter of time that warfarin is replaced, maybe not today, not tomorrow but it is not too far off now.

I like the thought of us advancing medicine to come out with safer and more efficacious treatments, but the FDA is so much more strict than it was years ago. Everybody makes a huge deal about Multaq's ADRs, but have you looked at the profile for amiodarone? Same thing with Chantix and suicidality; people want the drug pulled. What about all the SSRIs? They carry the same risk, if not greater. By no means am I saying we should just approve everything, but I think it's going to be a lot harder to find new drugs. There's no way warfarin would be approved with today's standards with all the ADRs and drug interactions.

 

[xiphoid2010]

I like the thought of us advancing medicine to come out with safer and more efficacious treatments, but the FDA is so much more strict than it was years ago. Everybody makes a huge deal about Multaq's ADRs, but have you looked at the profile for amiodarone? Same thing with Chantix and suicidality; people want the drug pulled. What about all the SSRIs? They carry the same risk, if not greater. By no means am I saying we should just approve everything, but I think it's going to be a lot harder to find new drugs. There's no way warfarin would be approved with today's standards with all the ADRs and drug interactions.

no argument there. My dad's on Multaq when that news hit, and he nearly freaked out. LOL

Warfarin will still be around, probably for a few decades more, but increasingly as a niche/fall back anticoag drug. The constant need to monitor INR, higher risk of ICH and the 2407502458 drug interactions, category x... just makes it a really dirty and ugly drug. It's the devil we know, but it's still the devil.

 

[spacecowgirl]

I like the thought of us advancing medicine to come out with safer and more efficacious treatments, but the FDA is so much more strict than it was years ago. Everybody makes a huge deal about Multaq's ADRs, but have you looked at the profile for amiodarone? Same thing with Chantix and suicidality; people want the drug pulled. What about all the SSRIs? They carry the same risk, if not greater. By no means am I saying we should just approve everything, but I think it's going to be a lot harder to find new drugs. There's no way warfarin would be approved with today's standards with all the ADRs and drug interactions.

Yes, but dronedrone was marketed largely as the "safer" amiodarone. Then you have all of these ADRs coming out. I'd rather stick with something that's been around forever and all of the risks (and there are many) are well known. For some reason I have a better gut feeling about Xarelto than Pradaxa. I certainly would be happy about anything that could adequately replace warfarin. I don't think it will be long before we see the indications for both (try to) expand.

I read a good article about the explosion of non-inferiority testing and ITT models. I'll have to dig it up because I do think it is applicable to what we are discussing with these medications.

IIRC, the cost for both Pradaxa and Xarelto is about $8/day.

 

[spacecowgirl]

xiphoid - I still don't understand your switcheroo business. Transitions of care are hard enough, I wouldn't mess with all of that back and forth stuff.

 

[xiphoid2010]

Pradaxa got put on the formulary at the hospital I interned at this summer. In fact, I was at P&T when it got approved. My clinical coordinator was against it and the cardiologists were trying to get approved for more than 6 months. Anyways, isn't Pradaxa more like $10 per pill and it's BID so ~$20/day? I definitely think there is a big cost difference especially for the patient after discharge, making compliance an issue.

Missed your post.

It shouldn't be that expensive. My acquisition cost for them is ~$6.50 a day, that includes dabigatran 150 mg bid. Even the AWP on them ~$8.50 a day. I don't see how they are coming up with $20 per pill... unless they are counting some huge pharmacy dispensing fee? But they have to add the same fee to warfarin, although the acquisition cost of that is 14 cents a day, not counting labs.

Pharmacy has traditionally resisted newer and more expensive meds. A lot of it is silo mentality. Pharmacy department's budget is seen as separate from other departments in the hospital. We rather let another department pay, for exampble INR labs, while we keep the pharmacy cost down. Of course that's not the way it should be, but that's just how things work in a hospital, each department trying to cover their own budget even though all the money comes from the same pot in the end.

 

[xiphoid2010]

xiphoid - I still don't understand your switcheroo business. Transitions of care are hard enough, I wouldn't mess with all of that back and forth stuff.

Relax girl. I'm considering whether to add these drugs to our formulary, and giving the admitting physicians the options to switch. It's by no means a mandatory change.

There are pros can cons, hence the question, is the avoiding drug interactions and the constant INR/dose adjustments worth the hassel or produce better outcome (at least inpatient). I wish there is a study out there to answer this question, but there isn't.

 

[spacecowgirl]

I will not relax!!!!11!!!

Found those articles about non-inferiority trials

http://pharmacotherapyjournal.org/doi/abs/10.1592/phco.31.9.831

http://pharmacotherapyjournal.org/doi/abs/10.1592/phco.31.9.833

 

[gotdrugs]

Relax girl. I'm considering whether to add these drugs to our formulary, and giving the admitting physicians the options to switch. It's by no means a mandatory change.

There are pros can cons, hence the question, is the avoiding drug interactions and the constant INR/dose adjustments worth the hassel or produce better outcome (at least inpatient). I wish there is a study out there to answer this question, but there isn't.

Again, even if it's just going to be recommendations - if you are going to switch anybody's anticoagulation back and forth, I would still strongly encourage you read the data (and the outcomes) that has been discovered regarding the risks of doing so.

Just a suggestion.

Now, if the switch is a one-time thing and they go home on pradaxa.......well that's logical and a different story.

But to recommend switching just for inpatient stay then switching back at (or close to) discharge.....good luck with that.

 

[gotdrugs]

Everybody makes a huge deal about Multaq's ADRs, but have you looked at the profile for amiodarone?

You do know the one big difference in the known data re: amiodarone and dronedarone that has even educated people concerned about Multaq right?

Hint: It's the biggest "ADR" of all..........

 

[xiphoid2010]

Again, even if it's just going to be recommendations - if you are going to switch anybody's anticoagulation back and forth, I would still strongly encourage you read the data (and the outcomes) that has been discovered regarding the risks of doing so.

I will be presenting these 2 drugs, and I know MDs will ask for my opinion. Just thinking ahead where my personal opinion would be. Given how poorly INR is controlled/followed in an acute setting and how many drug interactions is unavoidable/missed/ignored, I see mostly upside if warfarin is switched during the inpatient stay from a safety and outcomes stand point.

Now, you are right that the what happens at or after discharge is an entirely different beast. But please point me towards any data you have on outcomes of Pradaxa or Xarelto switching, because my pub-med search hasn't turned up anything. I agree that if medrec and discharge consoling is not done, it can end up badly outpatient, but that's an educated guess. So maybe I will throw that in when I present my opinion.

 

[xiphoid2010]

For those who wants to know:

Just heard back that at my hospital, PT/INR cost $6.04 (lab can't do INR only)

So basically, for an inpatient setting, cost of Pradaxa or xarelto = warfarin + daily INR (not counting the cost of MDs/RPh/RN spend trying to keep it in range)

 

[gotdrugs]

I will be presenting these 2 drugs, and I know MDs will ask for my opinion. Just thinking ahead where my personal opinion would be. Given how poorly INR is controlled/followed in an acute setting and how many drug interactions is unavoidable/missed/ignored, I see mostly upside if warfarin is switched during the inpatient stay from a safety and outcomes stand point.

Now, you are right that the what happens at or after discharge is an entirely different beast. But please point me towards any data you have on outcomes of Pradaxa or Xarelto switching, because my pub-med search hasn't turned up anything. I agree that if medrec and discharge consoling is not done, it can end up badly outpatient, but that's an educated guess. So maybe I will throw that in when I present my opinion.

Didn't say pradaxa or xarelto switching, but anticoagulation switching and what can happen. I doubt there is specific pradax or xarelto data on this due to their "newness." OTOH, if you think they are exempt from the risks that have been shown by multiple switches of anticoagulants in the past, then I would respectfully disagree.

 

[gotdrugs]

I will be presenting these 2 drugs, and I know MDs will ask for my opinion. Just thinking ahead where my personal opinion would be. Given how poorly INR is controlled/followed in an acute setting and how many drug interactions is unavoidable/missed/ignored, I see mostly upside if warfarin is switched during the inpatient stay from a safety and outcomes stand point.

Now, you are right that the what happens at or after discharge is an entirely different beast. But please point me towards any data you have on outcomes of Pradaxa or Xarelto switching, because my pub-med search hasn't turned up anything. I agree that if medrec and discharge consoling is not done, it can end up badly outpatient, but that's an educated guess. So maybe I will throw that in when I present my opinion.

I understand you wanting to be prepared and thinking ahead. Just am giving advice as someone with a bit more experience than you (I'm taking a guess based off the observations of this thread) in order to give the best opinion, you probably need to know all the data, ramifications, data regarding the ramifications and logistics when you are making recommendations like this, esp in the setting of high-risk meds.

If you have someone in the audience who knows the info like I, then you lose credibility. If you were to go with a system-wide switch (which I understand you say that wasn't your intent, but until you clarified that, it seemed that way) and you had bad outcomes, then you lose credibility.

Gotta look at it from more than just a pure acquisition cost issue. It's the things like that where prescribers get into their head pharmacy is only there to try to reduce costs to the hospital.

 

[xiphoid2010]

OTOH, if you think they are exempt from the risks that have been shown by multiple switches of anticoagulants in the past, then I would respectfully disagree.

I'm not disagreeing. I am actually hoping that you can show me some study data. I searched Pubmed using key words "autoconversion", "autosubstitution", and "drug switching" and came up with no study related to this area.

You are correct that I'm new to this whole thing. I'm newly hired on as the ID/pharmacy manager right out of residency. Since I'm the only clinical pharmacist on staff, it falls upon me to present at all these meetings, lucky me. The pharmacy director got promoted to corporate so not fully here, I'm left trying to keep thing together for a while. Lucky me.

 

[a runner]

Missed your post.

It shouldn't be that expensive. My acquisition cost for them is ~$6.50 a day, that includes dabigatran 150 mg bid. Even the AWP on them ~$8.50 a day. I don't see how they are coming up with $20 per pill... unless they are counting some huge pharmacy dispensing fee? But they have to add the same fee to warfarin, although the acquisition cost of that is 14 cents a day, not counting labs.

Pharmacy has traditionally resisted newer and more expensive meds. A lot of it is silo mentality. Pharmacy department's budget is seen as separate from other departments in the hospital. We rather let another department pay, for exampble INR labs, while we keep the pharmacy cost down. Of course that's not the way it should be, but that's just how things work in a hospital, each department trying to cover their own budget even though all the money comes from the same pot in the end.

Yeah, it was my clinical coordinator (the same one who fended off Pradaxa going formulary for 6 months) that gave me that information, so she may have been biased. I guess she was exaggerating or it was higher for our hospital, but I did find online from the manufacterer that acquistion price is supposed to be ~$6.75/day, so that's in line with your prices.

 

[xiphoid2010]

The medical team meeting today went extremely well. Woohoo!

The MDs were pretty quite after the presentation. Only had a few minor questions asking for extra info which I had looked up in anticipation. No ambiguous "should I use this" questions were asked. Either they were all in a good mood or just too busy eating all the food. 😀

 

[ttopping]

The medical team meeting today went extremely well. Woohoo!

The MDs were pretty quite after the presentation. Only had a few minor questions asking for extra info which I had looked up in anticipation. No ambiguous "should I use this" questions were asked. Either they were all in a good mood or just too busy eating all the food. 😀

Glad your meeting went well! I actually presented a monograph for rivaroxaban about a month ago to our therapeutics committee. I mostly went over the RECORD studies since that's what it's indicated for (and the ortho docs at our smaller sister hospital have been asking about it). We approved it for its indication in ortho patients and will probably revisit the issue if the FDA decides to approve it for afib (potentially by Friday). I briefly touched on ROCKET-AF and why it was so much different than RE-LY (and why it's difficult to compare them) but not in too much detail since we didn't come to a decision in the anticoag subcommittee. The FDA has been so back and forth with it I honestly have no idea what they'll do.

 

[xiphoid2010]

Glad your meeting went well! I actually presented a monograph for rivaroxaban about a month ago to our therapeutics committee. I mostly went over the RECORD studies since that's what it's indicated for (and the ortho docs at our smaller sister hospital have been asking about it). We approved it for its indication in ortho patients and will probably revisit the issue if the FDA decides to approve it for afib (potentially by Friday). I briefly touched on ROCKET-AF and why it was so much different than RE-LY (and why it's difficult to compare them) but not in too much detail since we didn't come to a decision in the anticoag subcommittee. The FDA has been so back and forth with it I honestly have no idea what they'll do.

RECORDs studies had some serious flaws. Only 1 and 4 compared xarelto to properly dosed Lovenox. And while excess bleeding during each trial were not statistically different, combined all the data it does become significant, although not enough to outweigh the benefits.

I'll track these drugs for the next couple of months. If there is enough demand, I'll take pradaxa to p&t. I'll wait off on xarelto for now since apixaban also looks promising.

 

[ttopping]

RECORDs studies had some serious flaws. Only 1 and 4 compared xarelto to properly dosed Lovenox. And while excess bleeding during each trial were not statistically different, combined all the data it does become significant, although not enough to outweigh the benefits.

I'll track these drugs for the next couple of months. If there is enough demand, I'll take pradaxa to p&t. I'll wait off on xarelto for now since apixaban also looks promising.

While I'll definitely agree there were plenty of flaws, I don't know if I'd say they were serious. Despite the dosing issues, the results were all relatively similar. I feel like a potential issue which made it difficult to recommend is that a lot of hospitals use dalteparin preferentially over enoxaparin anyway so it's hard to extrapolate. Although I see your point with the bleeding, I'm not sure combining data from different studies using different doses and different lengths of therapy really means anything. The evidence doesn't necessarily scream that rivaroxaban is better, but it certainly doesn't point to worse outcomes. Plus it's oral, once daily, and cheaper then enoxaparin or dalteparin.

Apixaban does look promising although it probably won't be up for approval until sometime next year. I just think it's nice to have other options for patients who have difficulties with warfarin although I doubt we'll get to that "overall better drug" point anytime soon. I'm not convinced about dabigatran or rivaroxaban at this point, as the first already has issues, and the second is getting criticized before anything even happens with it.

 

[Ackj]

RECORDs studies had some serious flaws. Only 1 and 4 compared xarelto to properly dosed Lovenox.

Apparently that's how they dose Lovenox in Europe. 😕 At least that's a very good excuse to say they were purposely using a poor dose to trump up their data.

 

[ttopping]

Apparently that's how they dose Lovenox in Europe. 😕 At least that's a very good excuse to say they were purposely using a poor dose to trump up their data.

Is it really a poor dose? Are there studies that directly compare the use of 40mg once daily and 30mg q12h? Or were those doses approved just because that's what was studied more? I'm genuinely curious because I don't know that literature very well. Also, I don't think fragmin is actually approved for VTE prophy in those patients and we still use that.

 

[Ackj]

Is it really a poor dose? Are there studies that directly compare the use of 40mg once daily and 30mg q12h? Or were those doses approved just because that's what was studied more? I'm genuinely curious because I don't know that literature very well. Also, I don't think fragmin is actually approved for VTE prophy in those patients and we still use that.

I'm not sure that I've seen a direct comparison. The 30mg performed better than the 40mg, but those were two different studies. Personally, I've only seen the 30mg q12 dose used before.

RECORD 3: 166/878 (18.9%) on 40mg had a VTE vs 79/824 Xarelto (9.6%)
RECORD 4: 97/959 (10.1%) on 30mg q12 with VTE vs 67/965 Xarelto (6.9%)

http://www.xarelto.com/en/clinical-...edic-surgery/total-knee-replacement/index.php

 

[ttopping]

I'm not sure that I've seen a direct comparison. The 30mg performed better than the 40mg, but those were two different studies. Personally, I've only seen the 30mg q12 dose used before.

RECORD 3: 166/878 (18.9%) on 40mg had a VTE vs 79/824 Xarelto (9.6%)
RECORD 4: 97/959 (10.1%) on 30mg q12 with VTE vs 67/965 Xarelto (6.9%)

http://www.xarelto.com/en/clinical-...edic-surgery/total-knee-replacement/index.php

I'm aware of the RECORD studies, and I know those pretty well. I meant prior to, and why the doses used were "wrong"

 

[xiphoid2010]

I'm aware of the RECORD studies, and I know those pretty well. I meant prior to, and why the doses used were "wrong"

Look at the 2008 Chest guideline on DVT prophy. Basically hip and knee surg are pretty much the highest DVT risk ones. Without prophy, DVT develops s/p hip like 10-20%, knee 40-60%. But risk for DVT s/p hip extends out up to 3 months, while knee risk duration tends to be shorter.

Anyway, it's been a while since I read the guideline. But I think the recommendation is that these patients be given high risk dose prophy. Although 40 mg daily is approved for s/p hip surg, what I seen in practice is that 30 mg bid is often used for these since it's is more efficacious. Lovenox has pretty short half life, so I can see bid dosing makes more sense in high risk patients.

At the VA, arixtra is used instead. I think there was studies that showed it was better than lovenox in these patients. I'm guessing it's he longer half-life.

 

[spacecowgirl]

Rivaroxaban - now has AF indication...

http://www.medscape.com/viewarticle/752961?sssdmh=dm1.731407&src=nl_newsalert

 

[joetrisman]

Rivaroxaban - now has AF indication...

http://www.medscape.com/viewarticle/752961?sssdmh=dm1.731407&src=nl_newsalert

I have a test monday over VTE, PAD, ACS, AF, cardio, cardio, cardio...and I'm REAAAAALY hoping that will be a "wrong" answer on the test

 

[CUpharmD2013]

I have a test monday over VTE, PAD, ACS, AF, cardio, cardio, cardio...and I'm REAAAAALY hoping that will be a "wrong" answer on the test

Yeah, we had a test on Friday and the alert came out while I was taking the test.

 

[spacecowgirl]

Thought this was interesting.

Especially this part "The FDA said the median TTR for warfarin in general use is about 65%, but in ROCKET AF, the TTR was only a “relatively poor” 55% (http: //tinyurl.com/3tq4sst). A lower TTR than seen historically suggests any medication being compared with warfarin will look better"

 

[ttopping]

Thought this was interesting.

Especially this part "The FDA said the median TTR for warfarin in general use is about 65%, but in ROCKET AF, the TTR was only a "relatively poor" 55% (http: //tinyurl.com/3tq4sst). A lower TTR than seen historically suggests any medication being compared with warfarin will look better"

Median TTR (as reported by what means...) in a general population (not just afib patients) is a lot different than an average TTR in 14,000 patients in a single study though. I think the point is that warfarin is difficult to control even in a controlled trial situation. It's sad to think we're trying to compare TTR to a mean of 65%...seems so pathetic. The patients were also a lot sicker in the ROCKET-AF trial compared to RE-LY and ARISTOTLE, and 62% had previous warfarin use at baseline (so maybe they were the difficult to control patients). Do I think rivaroxaban is great for abif? Meh, not necessarily, however it may be beneficial for those patients who are difficult to control on VKA. No trial is going to be perfect, and I certainly don't think the flaws in ROCKET skew the data so much to say that it's inferior to warfarin. I mean, with better control over warfarin, it may have even shut down dabigatran. Just some thoughts

 

[Ackj]

ATLAS results have been published. This one studied rivaroxaban for post-ACS thrombosis.

http://www.nejm.org/doi/full/10.1056/NEJMoa1112277