From Pradaxa to Coumadin and Back

[bill hall]

I had my surgery over a week ago and they had prescribed Pradaxa for my irregular heartbeat several weeks prior. Before surgery, they told me I should stop Pradaxa three days prior to surgery. I did an extra day, so stopped four days before surgery. During the surgery, I had excesssive bleeding that required transfusions. I think it was two days after surgery when they started Coumadin, since my heart was still irregular. My INR number spiked up just before leaving the hospital, similar to my previous surgery. They stopped the Coumadin and measured twice this week, to see when it will be safe to restart Pradaxa. Anyway, they told me it was OK to restart Pradaxa, but I decided not to restart Pradaxa. The evidence is strong that my blood overreacts to the blood thinning products. I may go back to coumadin where there is some measurement and feedback or go back to a daily aspirin. Any feedback is appreciated.
Bill

 

[AgilityDog]

Well, if you decided not to take the pradaxa, make sure your doctor KNOWS. If you have an irregular heartbeat you may be putting yourself at risk of a stroke without some anticoagulation, either pradaxa or coumadin. Discuss with your doctor. Aspirin may not be enough.

 

[Jkm7]

Decisions regarding anti-coagulation should never be made without consult with your doctors. This is not a decision you should be making on your own or advice from an internet message board. To have chosen to ignore doctor's advice about stopping/starting coagulation medications was very risky and not advised.

Certainly let your doctors know your thoughts and questions, but please speak directly with them. If you are not comfortable with their advice, seek other medical professionals to assist you in making these important decisions.

Best Wishes.

 

[Protimenow]

You didn't indicate what type of surgery you had (I'm assuming that it was NOT a heart procedure), but it might be helpful to know this. Obviously, since you were taking Pradaxa, you have atrial fibrillation.

Warfarin has been used for A-fib for years - possibly decades - and it is effective for most patients taking it. In some cases, less effective medications (like aspirin, for example), have been enough for minor cases of A-fib.

Pradaxa is new, expensive (especially when compared to generic warfarin), and not always easy to control. (As can be seen by your bleeding problems even after stopping it before surgery -- imagine what additional problems you may have had if you had stopped when the doctors advised you to).

The great deal of money that is being made with Pradaxa helps fuel a drug rep juggernaut that convinces doctors that it's either better or safer than warfarin (which makes the drug companies little profit) and an advertising blitz that has patients thinking that it's the only choice for their A-fib and asking the doctors about it.

Warfarin is relatively easy to manage. If you have a meter, it's easy to test your blood, and, with the doctor or an anticoagulant clinic's advice, it should be pretty easy to manage your anticoagulation status, once you've found the right dose for your body.

As the others have said, don't decide to start or stop a particular anticoagulant without consulting with your doctor or an anticoagulation clinic.

(That said, I'm personally not exactly following that advice. With no doctor and no insurance, I self-test and self-manage my dosing. I test weekly. Many others are also able to self-test and manage their dosing, and there are useful charts for doing so. Because I have a mechanical valve, Pradaxa isn't an option for me -- but even if it WAS, I'll stay with warfarin because it's much less expensive than Pradaxa, it's possible to reverse any effects of over-anticoagulation (which you apparently can't do with Pradaxa), it's possible to test for the effects of warfarin (simple INR testing -- I don't know if the effects of Pradaxa show up in INR), and warfarin has a proven history after decades of use. If you know what you're doing, warfarin is relatively safe and effective).

But, again, work with your doctors to figure all this out -- and be careful if they try to bully you into returning to Pradaxa. I don't work for the company that makes Pradaxa or any companies that manufacture coumadin or generic warfarin, so the only stake I have in this is to help you keep your mind open to the best anticoagulant choices. What you ultimately do is between you and your medical team -- and, remember, it's YOUR life.

 

[ElectLive]

As the others said, first things first, definitely don't discontinue or switch anticoagulation on your own, please discuss with medical professionals. Pradaxa is only for AFib not caused by heart valve problems, I assume (and hope) that's the case for you?

Pradaxa is the new drug on the block. As such, I think it's only fair for you to expect a complete explanation from your doctor as to why it's better for your situation. Warfarin has over 50 years of evidence while Pradaxa has 1 year. In my opinion, the burden of proof should be on any doctor recommending Pradaxa over Warfarin right now. Maybe it is in fact better for you. I'm not saying it's not. I'm just saying that you should want and expect from your doctor a full disclosure on all the knowns, unknowns, risks, etc. Things like dosage and noncompliance, monitoring, bridging procedures, emergency reversal protocol, and yes, cost too. Many of these issues seem "iffy" at best to date.

You will also find the prescribing safety information on the Pradaxa website. It includes things like surgeries and switching back and forth with Warfarin: http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing%20Information/PIs/Pradaxa/Pradaxa.pdf

 

[Lynlw]

Decisions regarding anti-coagulation should never be made without consult with your doctors. This is not a decision you should be making on your own or advice from an internet message board. To have chosen to ignore doctor's advice about stopping/starting coagulation medications was very risky and not advised.

Certainly let your doctors know your thoughts and questions, but please speak directly with them. If you are not comfortable with their advice, seek other medical professionals to assist you in making these important decisions.

Best Wishes.

I agree with JK on everything she said. This isn't something you want to play around with when the risks are so high, it would be awful to have a stroke IMO.
Since you were on Pradaxa quite a while without any problems before your surgery, I personally would prefer to be on it over Coumadin, beside the fact you dont need testing, it doesn't affect Vitamin k and doesn't interact with many foods or other meds, in the RELY trials comparing pradaxa vs Coumadin FOR AFIB the patients on Pradaxa did much better.

Here is one of the article discussing the results Conducted at 951 centers in 44 countries, the trial had randomized 18 113 patients with AFIB

http://www.theheart.org/article/995769.do
RE-LY: Oral antithrombin dabigatran outshines warfarin in atrial fib

An oral anticoagulant that does not go by the name of warfarin prevented strokes and peripheral embolic events in patients with atrial fibrillation (AF) significantly better than that much older drug at a higher dose and just as well at a lower dose in a huge randomized trial [1]. It was also just as safe as warfarin or better than it, respectively, with respect to major bleeding events, according to investigators reporting today at the European Society of Cardiology (ESC) Congress 2009 and in a simultaneous online release from the New England Journal of Medicine. Both dosages were associated with fewer intracerebral bleeds


The potential new contender in AF, dabigatran etexilate (Boehringer Ingelheim), is one of several oral anticoagulants in clinical trials for the prevention of AF-related thromboembolism, venous thromboembolism (VTE), and other conditions for which warfarin had long been the only choice. A competitive thrombin inhibitor, dabigatran is currently available for VTE prevention during hip- and knee-replacement surgery in the European Union as Pradaxa and in Canada as Pradax.

In the new trial, the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY), dabigatran given at 150 mg twice a day reduced the annualized risk of the primary end point, stroke/peripheral embolic events, by 34% (p<0.001) and the risk of hemorrhagic stroke by 74% (p<0.001) compared with warfarin. The higher dabigatran dose was associated with a slightly but significantly (p=0.048) increased risk of MI, a secondary end point.

"I think this is a dramatic study with very definitive results," Dr Michael D Ezekowitz (Lankenau Institute for Medical Research, Wynnewood PA) told heartwire. "Both doses for different reasons were better than warfarin. So the results of the trial were unequivocal." Ezekowitz is one of the trial's lead investigators and a coauthor on the report...... more at link

 

[lance]

Too bad the researchers didn't refer to lack of a reversal in case of a bleed. Without testing there is no way of knowing the level of this drug in the system. On another board I've read of bleeding events in either Australia or NZ. So I'd regard this drug with suspicion for now just as coated heart valves should have been when touted by manufacturer's sales teams some years ago.
AND
there's much money to be made on this new drug.

 

[Bev]

I have a friend who just went off Pradaxa and back on warfarin, as it was making her arthritis so much worse after being on the drug for about 3 months. Something to think about if they ever approve Pradaxa for us heart valve patients.

 

[bill hall]

Thank you all for the useful information. I did see my PCP yesterday and we decided to go back to coumadin. Sorry if I implied I was just dropping Pradaxa. I did have my aortic aneurysm fixed with my surgery of Oct 12.
Thanks - Bill

 

[ElectLive]

It is good that Lyn posted some of the RE-LY results. As she noted, for that particular AFib patient group, from a stroke standpoint, there did seem to be very positive results. We should not lose sight of the potential "pros" when pointing out the potential "cons". It is important to continue to note here, though, that the RE-LY trial had very specific patient criteria and excluded patients with a prosthetic heart valve, reversible causes of A-Fib (such as cardiac surgery), hemodynamically relevant valve disease and/or pending surgery among other exclusion criteria. Since so many of our members here meet one of more of those criteria, I wonder how much importance those that do should give the RE-LY results, since our particular patient group was not "represented" in the trial.

Bill - Your situation, from the little I know or remember, is interesting relative to some of these issues. You have a homograft that did not end up needing to be replaced, right?

As I stated, this may purely be an academic discussion for most of us, since the data may not be relevant. But for what it's worth: the link I posted above did include some of the "cons" from the RE-LY trial as well. There was a slightly higher (21% vs 15%) discontinuation rate for Pradaxa compared to Warfarin due to bleeding and GI issues. There was a higher incidence of major bleeding with Pradaxa in the 75 and up age group. There was a higher incidence of major GI bleeds and GI reactions on Pradaxa in all patients. But, to be fair, intracranial bleeding was lower with Pradaxa. It's noted also that the mean percentage time in therapeutic range (INR 2-3) was 64% for those patients randomized to Warfarin. This seems low to me, but I'm not one to judge, maybe I'm being unrealistic since I'm not on ACT. My point would be, though, a higher percentage of time in therapeutic range could have improved the Warfarin results.

Sorry to ramble (particularly on your thread Bill!) but I have a family member whose doctors are going through these considerations hence my great interest. I kind of have this feeling it could end up in a similar situation to heart valves where half the patients and doctors believe in Warfarin and half the patients and doctors believe in Pradaxa, no definitive answer. Who knows, it will be interesting. My thoughts probably aren't helping much, so in closing, here's what the ACC/AHA have to say (http://circ.ahajournals.org/content/123/10/1144.full?ijkey=29e0c0d94f877de091f78345abc3a3ac111b9418&keytype2=tf_ipsecsha ):

"Dabigatran is useful as an alternative to warfarin for the prevention of stroke and systemic thromboembolism in patients with paroxysmal to permanent AF and risk factors for stroke or systemic embolization who do not have a prosthetic heart valve or hemodynamically significant valve disease, severe renal failure (creatinine clearance <15 mL/min), or advanced liver disease (impaired baseline clotting function).(3) (Level of Evidence: B)...

Because of the twice-daily dosing and greater risk of nonhemorrhagic side effects with dabigatran, patients already taking warfarin with excellent INR control may have little to gain by switching to dabigatran. Selection of patients with AF and at least 1 additional risk factor for stroke who could benefit from treatment with dabigatran as opposed to warfarin should consider individual clinical features, including the ability to comply with twice-daily dosing, availability of an anticoagulation management program to sustain routine monitoring of INR, patient preferences, cost, and other factors."

 

[Protimenow]

EL - thanks for the materials, and the interesting perspective they present.

In Bill's case, even though he stopped Pradaxa four days before surgery (he was told to stop 3 days before), he still had a bleeding problem. I'm still somewhat concerned that Pradaxa can't easily be reversed.

Your report on the mean percentage of time patients stay in therapeutic range is a bit troubling. There are reports saying that people who self-test have a higher amount of time IN range than those who aren't self-testing. The study doesn't mention whether these are self-testers or people who had to go to a lab for testing.

For people who CAN self-test, I suspect that the mean percentage of people in range would be better. More time in range may also reduce the number of strokes (because there would be fewer people at the low end of the range and more likely to form a clot). Here's another reason why I think everyone who CAN self-test SHOULD self-test, and why I firmly believe that testing weekly is a GOOD thing - even for people who believe that their INRs are consistently in range, based on less frequent testing.

 

[Lynlw]

Too bad the researchers didn't refer to lack of a reversal in case of a bleed. Without testing there is no way of knowing the level of this drug in the system. On another board I've read of bleeding events in either Australia or NZ. So I'd regard this drug with suspicion for now just as coated heart valves should have been when touted by manufacturer's sales teams some years ago.
AND
there's much money to be made on this new drug.

There are ways to test pradaxa, it just isn't routinely needed since everyone gets the same dose. As for reversals, since it has a short half life, which is why you need to take it every 12s hours, depending on how close it ws to your last dose, if it was shortly before they could use charcol to absorb some of it and it if was close to when you need the next dose, much of it would already be gone, and in cases of trauma, my guess is they would give clotting factors and various blood products (Red cells, FFP cryo platelets) like they do in most traumas and even in coumadin patients beside giving them vitamen K or FFP if they are bleeding.

Yes there have been reports of severe bleeds, but there are for any anticoagulant. Im not saying I wouldn't be suspicious but to ME, it has alot of plusses for it instead of coumadin in patients its a approved for.

 

[ElectLive]

Your report on the mean percentage of time patients stay in therapeutic range is a bit troubling. There are reports saying that people who self-test have a higher amount of time IN range than those who aren't self-testing. The study doesn't mention whether these are self-testers or people who had to go to a lab for testing.

For people who CAN self-test, I suspect that the mean percentage of people in range would be better.

I have no idea about the form of testing, but would guess lab since it was a clinical trial and would likely need proper verification. Here's some additional info (http://www.pradaxapro.com/RELY.jsp):

"Study Design

•2 blinded doses of PRADAXA were compared to open-label warfarin adjusted locally to an international normalized ratio (INR) of 2.0 to 3.0, with the INR measured at least monthly

Time in Therapeutic Range

•Mean percentage of time in therapeutic range (INR 2.0-3.0) was 64% for patients randomized to warfarin
◦Mean percentages of time INR measurements were greater than 4.0 or less than 1.5 were 2% and 5%, respectively
•Median percentage of time in therapeutic range was 67% for patients randomized to warfarin"

So, "at least monthly", who knows what that really means (more often in the majority of patients?, only a few?, etc). One natural question is: do those study criteria and results really constitute well controlled warfarin? The Pradaxa website says repeatedly that the stroke "risk reduction was greatest when compared to AFib patients on warfarin whose blood tests showed lower levels of control." Perhaps this is why the ACC/AHA take the position they do, that Pradaxa is a more natural alternative for those patients not doing well with Warfarin (poor control, for example) but not so much for those who are already under good control and compliance.

 

[Luana]

There are ways to test pradaxa, it just isn't routinely needed since everyone gets the same dose. As for reversals, since it has a short half life, which is why you need to take it every 12s hours, depending on how close it ws to your last dose, if it was shortly before they could use charcol to absorb some of it and it if was close to when you need the next dose, much of it would already be gone, and in cases of trauma, my guess is they would give clotting factors and various blood products (Red cells, FFP cryo platelets) like they do in most traumas and even in coumadin patients beside giving them vitamen K or FFP if they are bleeding.

Yes there have been reports of severe bleeds, but there are for any anticoagulant. Im not saying I wouldn't be suspicious but to ME, it has alot of plusses for it instead of coumadin in patients its a approved for.

Ways to test if one is in therapeutic range with Pradaxa, what are they? Short half-life does not mean much when a person can die of an internal bleed in a matter of minutes. From what I've heard, vitamin K and blood transfusions are not antidotes for Pradaxa. Reports of severe bleeds? How about 260 deaths from bleeding, as acknowledged by Boehringer Ingelheim this past week. Sounds like an awful high number to me when the drug has been in use less than a year and is probably only being prescribed so far to a small handful.

Have there been 260 deaths from bleeding from Coumadin in the past year? Why did the short half-life and vitamin K and blood transfusions not work for those 260 lethal events?

 

[Protimenow]

Good questions. It sort of makes me wonder if the FDA might have rushed approval if there have been this many fatal bleeds. It sort of makes me wonder why the FDA doesn't take another look at it (if they haven't already).

Of course, there may be thousands taking it, judging from all the commercials that are being shown pushing this medication.

It kind of makes you wonder how much risk a person should take -- is one death in 1000 people taking the drug too much (assuming that as many as 260,000 have taken it)? One in 100? I can't imagine the numbers being all that much higher.

Although warfarin should require fairly careful monitoring (although some doctors still seem to think that monthly testing is fine), I'm sure that it has a much better overall track record than this report about Pradaxa. (There was mention that Pradaxa was used in people with A-Fib who had problems keeping a stable INR. I wonder how often these people tested -- and if more frequent testing and minor tweaks of dosage - if necessary -- would have made the 'uncontrollable' group much smaller and the benefits of Pradaxa much lower)

 

[ElectLive]

I'm actually going to side with Pradaxa, but with conditions, on the headline grabbing number of deaths reported. On November 2nd, Boehringer released a statement indicating that there are already 450,000 patients using Pradaxa. The RE-LY trial had a higher number of deaths with a way lower patient population. According to the FDA advisory documents, there were 445 deaths in the RE-LY trial arm of Pradaxa 110, 437 deaths in the trial arm of Pradaxa 150, and 486 deaths in the trial arm of Warfarin. Each of these trial arms had just over 6000 patients. The yearly event rates for all-cause mortality in those same arms were 3.8%, 3.6%, and 4.1% respectively.

Now, with that said, I still think mortality rate is definitely not a selling point for Pradaxa. In fact, the original approval indication requested for Pradaxa included "reduction in vascular mortality." It was later withdrawn. The FDA documents reveal that it would not have been granted anyway for reasons such as faulty trial data methods, open-label impact on treatment bias, and most importantly, the impact of center level INR control. Pradaxa mortality rates were "superior" to Warfarin only at the centers with the poorest INR control. This was one of the reasons Pradaxa was given overall approval only as "non-inferior" to Warfarin, even with the better stroke numbers. Boehringer is allowed to advertise the better stroke numbers, but is not allowed to claim superiority to Warfarin.

The FDA tracks all the adverse events (minor and major) since it hit the market. One article I read indicated that about 1/3 of the events reported thus far were related to "off-label" use of Pradaxa. So, let's not forget the doctors in all of this too. If it is being prescribed improperly, that can also be a source of bad events.

 

[Protimenow]

Off-label is an interesting concept. It was useful for Minoxidil (which is now marketed as Rogaine), and off-label is continuing to be used with other drugs. However, the use of Pradaxa, off-label for valvers seems a bit premature, and quite possibly rather careless.

There are other drugs being developed that may, eventually replace warfarin as a drug of choice for prevention of clotting related to heart valves, but these are apparently still some years down the road. For myself, with all its problems, I'll probably stay with my 10-20 cent/day dose of warfarin. (I only wish the InRatio strips were less expensive so I can monitor more closely if I add a medication, change my diet, or fall out of range).