I believe that the main reason for the slow response to Pradaxa is cost.The retail price per year is as you say about $3000.Most seniors who dont have insurance cant afford this drug,and they have to pay for other drugs also. So their MD will use coumadin..We clearly have a two  groups of patients,those who can afford Pradaxa,and those who cant and are on coumadin (with its greater risks). Boehringer Ingelheim,the manufacturer is trying to recoup their investment over a short period of time.If it costs about 1 billion dollars to bring the drug to market ,and  $3000 a year for 1 patient using Pradaxa,if you divide the 1 billion dollars by $3000, you get 333,333 patient with AF .There are 2.3 million people in the US with AF,so it may take  only a few years for the company to get their money back.

Another reason for the slow response to use Pradaxa is that Medicare part D (United Healthcare) is doing everything it can not to approve the use of the drug.If there is a possibility that the patient's AF is valvular,or some other etiology, then United Healthcare wont approve the use of the drug.A member of my family had mitral valve surgery in1991.Recently she developed AF and the insurance company is saying that her AF is valvular in origin (approx 20 years later).Her cardiologist hasnt been able to convince United Healthcare that her AF is non valvular.So she pays for the drug even though she has the insurance.I suspect that this is happening with a lot of patients.

I have enthusiastically prescribed dabigatran, however I've gotten some push back by our local GI doctor. He tells patients and other referring doctors that the incidence of GI bleed exceeds that of warfarin, and this has been an unforeseen battle.

 

 

One mistake that many physicians make is in not grouping patients by age, when considering new drugs. AF in patients in their 40's and 50's seems to this observer to be quite different from AF in patients over 75.

The latter group has a larger percentage of acid reflux problems, which would lead them not to use this medication, cost aside. These patients are also looking at a  stroke in the not to distant future and one that will probably kill them within a month after it occurrs.s

There is also the dosage level. These patients, if I understand correctly, would be taking a total of 300mg. of Pradaxa per day. That's a lot of med. Translate that to mg/Kg of body weight. A 100 lb person would weigh about 45 Kg. This works out to about 7mg/Kg if I'm reading my conversion tables correctly. Not much by comparison to animal toxicity tests, I realize, but possibly significant if you consider all the other meds that older people take.

I would therefore suggest that your target patient group might be the younger ones with diagnosed AF. If these are scarce as hen's teeth then you have a serious marketing problem, but I think the 50 - 70 age group should yield a large enough population and many in this group are too young to worry about Medicare.

Good luck

Our practice consists of mostly older population (>70). Because of the cost and no antidote, we have been reluctant to prescribe. Also, the limitations to non-valvular AF has decreased the number of patients who would be candidates.

Maybe, at least in some settings, it is because warfarin is a more effective and safer medication that can actually be managed quite easily with INR self testing and online managment.  If one looks at the 50% of RE LY patients with the best INR control (time in therapeutic range or TTR > 67.2%), then the combined major endpoint (stroke and SEE, major bleed, MI, PE, and death), turned out to be about 5.5%/yr while the same combined major endpoint with either dabigatran regimen was about 7%/yr.  Further, in four recent small studies of INR self-testing with online management, two studies reported a TTR of 80% while virtually eliminating extreme INR values of < 1.5 or >5 where major event rates increase exponentially. Clinician time required for patient management was < 10 min/patient/mo in 2 studies with substantial improvement in patient satisfaction and quality of life.  It seems to me that we have been managing warfarin the same old inefficient and sub-optimal way for the past 30 to 50 yrs.  Use of modern technology offers the opportunity to improve INR control to a degree that - in large trials - has been associated with a 50% reduction in major event rates while reducing the time and expense of management for both patients and clinicians.

DISCLOSURE:  We conducted one of the 4 studies mentioned above with the support of the Chest Foundation's Distinguished Scholar in Thrombosis Award, and I have served as an unpaid consultant in the development of one of the four software systems used in the above mentioned trials.

Ref: Bussey HI, Transforming oral anticoagulation by combining international normalized ratio (INR) self testing and online automated management J Thromb Thrombolysis (2011) 31:265–274 [DOI 10.1007/s11239-011-0564-y] 

As a health professional who takes 150 mg. Pradaxa 2x daily, I find that I am tolerating this medication with no problems.  I would recommend that patients taking this medication be sure to take it after eating and not on an empty stomach.   I was screened throughly prior to being giving the medication and met all the criteria.   I chose not to take Warfarin as I am fully employed and the frequent blood testing needed would be extremely difficult.  

Great to get these comments and perspective. Thanks for taking the time to record your thoughts here. Keep 'em coming!

In New Zealand we have a single government body which purchases pharmaceuticals at an extreme discount. Dabigatran is fully funded from July 1st and cost concerns should not be factored into prescribers decision making. It will be interesting to see what uptake is like after that date. Concerns about GI bleeding, lack of reversibility and inability to monitor prior to DCCV remain. Some patients are requesting to switch but others may not be aware of the availability of the drug. Thought leaders are suggesting that switching should be considered in patients with oscillating INRs, outside of the therapeutic range. These may be the patients with the 2C9 variants who slowly metabolise warfarin, however there did seem to be a disproportionate number of patients with ICH in RE-LY, suggesting something else is going on. Did RE-LY have DNA collection? Hopefully the answer to that is yes, and a sensible decision can be made about switching.

I am a 72 yo male MD' semi-retired with h/o CABG 1987. First episode a-fib March of this year. Started on Dabigatran and on 3rd dose had such severe chest pain of GI origin I almost called 911. Read the cautions to patients and is stated that 35% of patients have GI complaints.

Went to my cardiologis and his fear of the drug is that it is not reversed quickly along with GI comlaits.

This drug will be a boon to the GI docs.

I don't think the marketing, for the introduction, was as good as it should have been for such an important medication.  Our rep seemd rather clueless and uninformed.  The cost should be lower, especially considering current economic conditions.  We need access to the 110 mg dose.  Otherwise, I use the medication as much as possible.

FACC

I am not a physician, but I am well-versed in matters concerning my health, and I have been following ALL the new anticoagulants for years, largely through theheart.org.  I waited anxiously for FDA approval, and I convinced my primary care physician (who had been in charge of my warfarin therapy) to Rx Pradaxa as soon as FDA approval was issued.  I got my first bottle of Pradaxa the very day that it hit the pharmacy shelves, and I started taking it a few days later as soon as my INR fell below 2.0.  I soon learned by trial and error that I could eliminate the dyspepsia by taking Pradaxa with meals (the package insert says that this is OK).  

With pretty good insurance, the net cost to me is about $90 for a 30-day supply.  I am retired (age 71), and it's well worth the $90 (compared to $5 for generic warfarin) not to have to fight early morning traffic (my PCP does blood work between 8:00 and 9:00 AM) to get my INR measured every few weeks.  I'm not sure if the high cost of Pradaxa would make it worth my while without any insurance support, but after having been liberated from the clutches of warfarin, I am inclined to think that it would. 

Another consideration that is hardly ever mentioned: Vitamin K supplementation is proscribed with warfarin (understandably), and over a five-year period on warfarin I have experienced mild bone demineralization.  Now, with Pradaxa, I can supplement with Vitamin K2 (in addition to the D3, calcium and magnesium that I had been taking all along).  That's another big plus for me.

When I visited my electrophysiologist (for controlled a-fib) a few months later, he seemed overjoyed when I told him that I had already converted to Pradaxa. He was surprised that he was getting only about 50% uptake for conversion to Pradaxa.

I hope that competition from apixaban and rivaroxiban, once approved for a-fib use, will bring down the price of dabigatran. 

The study which was used to get the drug approved showed a higher myocardial rate when compared to placebo

I wonder if dabigatran were the old drug and warfarin were new, how we might view them. One of these medications has no reliable way to measure its effect, and no reliable or measurable way to reverse its effect. The other has both. These might seem like very desirable qualities in a new anticoagulant medication, and I think we might take them for granted in warfarin.

I am a retired internist who has been taking warfarin for over 10 years for AF (now controlled) without problems. I can now do my own INR testing at home through the Coaguchek system offered by Roche and simply record it by telephone or online; it is then transmitted to the cardiologist's office for any dose adjustment required (same day). My problem with dabigatran is cost, need for twice a day dosing, inability to easily measure the degree of anticoagulation and the lack of an immediate antidote pre-op or post trauma. I might give it a try when the generic is available if I'm still around.

I just want to address 3 issues brought up:

 1.  The incidence of MI was not statistically significant on FDA mandated review

2 The discontinuation rate for dyspepsia was less tha 2% in RE-LY

3. For those with TTR in the highest quintile, there was no statistical difference in any endpoint, except lower ICH with dabigatran.

Having said that, I am uneasy with the drug in patients with borderline or variable GFRs arouund 30 to 35, particularly if they are on amio or dronedaroone. 

As a practicing cardiologist, I have been reluctant to jump on the pradaxa bandwagon for several reasons:

 

1. primarily, I am concerned about the cost.  Even if the pt doesn't have to pay the whole price out of his/her own pocket, the insurance company still has to pick up the tab, which means that we are still paying for it through insurance premiums.  I feel that we still have to be socially responsible and cost conscious whether it's ordering tests or prescribing medications.  For the same reason, I have never prescribed bystolic or coreg CR, because there are cheaper alternatives.  The price of Pradaxa may be 3000$ more per year, but multiply that by 5, 10, 20 years that the pt will be on the medication.  

 

2. With any new medication, there are always risks that side effects will come up later in post-market surveillance.  Ximeligatran had been studied extensively (there were 5 SPORTIF trials) before the liver toxicity caused it to be pulled.  Every week there's another article about the safety or lack thereof of TZDs (remember rezulin?).  I feel that it is prudent to wait until pradaxa has stood the test of time.  Few drugs will have the long track record of coumadin but when choosing between coumadin and pradaxa, the fact that coumadin has been relatively safely used for decades has to be part of the risk/benefit equation.

 

3.The field of oral anticoagulation is growing more rapidly than almost any in cardiac pharmacology (apixaban and rivaroxaban).  Undoubtedly, in the next few years we will have more experience and data to decide which medication is the best for AF.  I do not feel the need to jump to the first available agent.

 

All that being said, I have been using pradaxa for certain situations and find it to be very useful.  I like to use it for AF cardioversions.  As it is well known, cardioversion requires 3 wks of therapeutic anticoagulation prior to DCCV (or a TEE).  Also, pt's have to be on 4 wks of anticoagulation after.  Pradaxa helps make sure the pt is therapeutic before (instead of requiring the 3 wk counter to be reset if the INR is sub-therapeutic).  Similarly, after cardioversion (eg in inpatients with new AF), I would previously wait for the INR to be therapeutic before discharging a pt, but w pradaxa, I put the pt on pradaxa and discharge them the day of the cardioversion.  

 

Pradaxa has also been studied (RECOVER study in 2009), though not approved yet for DVT treatment, presumable pending RECOVER II.  This will also make it useful as a bridge to allow early discharge of pts saving the cost and inconvenience of hospitalization.  It is conceivable that some of these pts will be able to be treated entirely as outpts.

 

I have on occasion used it when patients have to stop their coumadin for surgery.  Previously, I might give pts LMWH or even admit them for heparin, but since the half-life is 12-17 hours (as opposed to 40hrs for coumadin, 4.5hrs for lovenox and 30-120 min for heparin) so if it is stopped 1-2 days prior to the surgery, it may be a reasonable compromise between minimizing CVA risk and avoiding bleeding complications.

  

My mother had 3 strokes in the past few years and this June 2011 she had transient ischemic attack and atrial fibrillation was finally caught to be the cause of her recurrent stroke. Her cardiologist and neurologist decided to give her Pradaxa 150 BID. It's been a week since she took Pradaxa and hopefully she would be doing fine with it and future strokes would be prevented. She is also taking cordarone.

Have used it now in 3 cases. Our health care system (Ontario) severely restricts its use due to the inability of most patients to pay.

 1. The first patient was a 60 year old priest who developed what appeared to be cardioembolic stroke on MRI. History of sleep apnea. Because he was young and had adequate private insurance, I had no qualms about starting dabigatran 150 mg BID (note that the 110 mg BID is available to us here as well).

2. The second patient was a 65 year old man with atrial fibrillation and carotid artery-related strokes. Interestingly, he started dabigatran, stopped it for a carotid stent, restarted it at the lower dose of 110 mg BID along with aspirin and plavix and did just fine (I insisted he also start a PPI).  He is now on low dose ASA and dabigatran 150 mg BID.  No bleeding issues and he is paying for it out of pocket ($120 Cdn per month, he reports).

3. The third patient is a 78 year old man who has had five cerebrovascular events despite aggressive antiplatelet therapy (ASA, clopidogrel and even naproxen for knee OA). Pending TEE he has been started on dabigatran 150 mg BID with ASA, clopidogrel and naproxen all stopped and his regular H2 antagonist continued. He likely has aortic atheromata thromboembolizing to his brain. Depending on the results of the TEE, and the likelihood he has a central source for these events, I think he will either continue dabigatran or start on warfarin which would be covered by the government.

Where can I find the data regarding the Dabigatran  vs best INR-controlled patient group?

You can find info on event rates vs INR control at the article that I cited in my initial post as well as the original work at Wallentin L, Yusuf S, Ezekowitz MD, et al (RE-LY investigators). Efficacy and safety of dabigatran compared with warfarin at different levels of international normalized ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet 2010 376:975-83

You also can find other information on dabigatran on the website, clotcare.org, where you also can contact me and/or our editorial board for more information. 

 I suffered a stroke fortunately controlled due to prompt treatment. Began to take Dabigastrin and after taking it (150 mg BID)  for 3 months, I noted having tarry stools. Stopped the Dabigastrin and the tarry stools terminated in four days.

I have been advised to take aspirin instead, but so it happened that i was indeed taking aspirin when I had my stroke, and obviously aspirin did not prevent it.

Would it be reasonable to resume Dabigastrin treament taking only 75 mg. BID and not 150 mg.? I understand that that Dabigastrin (Pradaxa) is available in 75 mg. doses.

Any comment would be appreciated.

 

 

 

AFib hit me by surprise at 65, found on a routine EKG.  I ran 2+ miles several times/week and was only slightly overweight.  I have been hypertensive basically all my life but have always been well controlled.  Coumadin was horrible.  My dosage required constant, almost daily, changes and my INR would not stabalize after three months.  Multiple INR tests were required/week. When dabigatran was approved, I consulted with several doctors to insure that I was a suitable candidate for the drug.  Because of my blood pressure meds, I had always been rate controlled with HR in the high 60s to low 70s.  Never an excursion above 85.  Dabigatran was started  once my INR fell below 2.0 and I have not looked back. There was some initial early morning stomach cramping, but that lasted only about 2 weeks.  Now, 7+ months into its usage, I am thrilled with the results.  A very recent echo shows an otherwise healthy heart with an ejection fraction of 67.  I stopped the med for 48 hours for cataract surgery and resumed it after no ill effects.  I remain very well rate controlled.  Small cuts can be a problem but I am never without some bandaids for those small cuts and I find increased bandaid pressure controls any bleeding in a relatively short time.  The best part of this drug for me is that after 35 years in management for a major corp., I pay $29 for a 3 month supply by mail order (from the US). Couple that with no INR testing and I am very happy with the result. 

I still can't get my head around the insistance from the medical community that we need to take very dangerous medications and poison our bodies "just in case". I have read and re-read all of the statistics involving ischemic strokes, anti-coagulants and the very real risks they cause (dangerous bleeds, hemorrhagic strokes, retinal bleeds with blindness, brain tissue and GI tissue destruction, etc.). When you sum the risks they introduce, the risks seem to OVERWHELM the risk reduction of ischemic stroke. I don't get it.

Anecdotally, I've lost friends to coumadin and warfarin, and nearly every month I run into someone else whose life was ruined by these drugs, yet I have talked to no-one in my circle who has had a stroke while NOT on anti-coagulants. I'm not dismissing the fact they occur, as obviously they do, but it appears from observation that the problems the drugs cause are far greater than the supposed benefit.

Is there ANYONE here that can convince me otherwise. If so, I would appreciate hearing from you and adding to my knowledge.I'm reluctantly taking Pradaxa, but I hate what it's doing to me and what activities I've had to stop ("Gee, I'd love to go rafting with you, but I can't - I'm anti-coagulated, you know. Hit my head and I'm dead")

 

- Peace

Hope 

I am a retired Veterinarian, 84 years old. Always active walking, bicycling etc. Had a mild stroke in 06, left me with a weekness of the left side but functional.. Was put on baby aspirin , stayed on that for many years. have controlled high blood pressure and always had a low puls rrate. a M.R.I done later showed, that I have had several T.I. A'.s.

 

I was put on Pradax 2 month ago simply because it does reduce the chance of a stroke. 110 mg. twice daily. I was diagnosed with atrial fibrillosis 3 month ago . I never outwardly had any symptoms from it, but the cardiologist suggested PRADAX. I do not have any side effects, always take all drugs with food, often use a banana. It would be nice if the insurance finally will carry some of the costs. My doctor and the googling convinced me that the chance to have a stroke is indeed reduced with PRADAX. To be debilitated by a stroke is no fun and we become a burden to our already suffering health system.

My cardiologist over a period of time put me on dabigatran after I was on warfarin. He has now put me on Xarelto because recently I have developed extremely painful GERD and gastritis. The latest Pradaxa medication guide  notes that "patients on PRADAXA 150 mg had an increased incidence of gastrointestinal adverse reactions....gastritis-like symptoms including GERD, esophagitis...&c. Xarelto, he believes, is more efficacious and will not cause these symptoms. I hope so too.

I'm concerned about discontinuation rebound effects. http://www.bmj.com/content/344/bmj.e3871?tab=responses There should be better studies on this.