I sure hope not! The behavior of big pharma with the new drugs, saying they do not need to be monitored, is for the  marketers only, not for the real world, in my opinion, You might look at Jelliffe R: Concerning Antiplatelet Therapy. A letter to the editor, Am. J. Cardiol., 2014;113:2086-2087. Be sure to look at the reply. It comes just after. The data must have all been there since Migliorini et al publish both the response (antiplatelet effect) and the outcome. There was NO search to find out WHO bleeds. Or WHO has a bad event. But the data HAS to be there.  It seems to me that NO ONE LOOKED for any relationship between effect and outcome. WHY? Because that goes counter to the advertised marketing strategy of BIG BAD PHARMA! The response (see the figure in the article referred to) ranged from almost none to almost total antiplatelet effect in both the tteatment groups. It seems to me that this is true of the marketing of essentially all the new NOACS. What a great opportunity is missed, as the new drugs may well be better, but no one seeks to optimize the therapy by wanting to monitor the anticoagulant or antiplatelet effect.

The lawyers see the results at both ends of the spectrum, and we see their ads on TV - call 1-800-BAD DRUG. What about 1-800 BAD PHARMA? What about 1-800 DUMB FDA? What about 1-800-POOR DOCS? Big Pharma, it seems to me, preys on the untrained physicians, who generally ask for and get NO OTHER training in how to give drugs except from Big Pharma. What a sad performance of the marketing of these drugs as the recent American Heart Assn meetings in Chicago! I will change my tone, and my anger, when I see a change in the ethical behavior of BIG BAD PHARMA, the poor behavior of DUMB FDA, and that of the POOR, PASSIVE, totally uncurious, UNTRAINED DOCS at the Am. Heart Assn.!

Hi,

just looking at the question, the easy answer is no, I do not think that vitamin K antagonists will not longer be used in the future. There still are a lot of new leasons on the new oral anticoagulants to be learned, one already has been learned: If you want to anticoagulate patients with terminal renal insufficiency, the NOAKs are not to be used... More will come, I am sure of that.

However, in some patient groups NOAKs might altogether replace vitamin K antagonists in the future...

So far, there is still one major setback for NOAKs: There is no direct antagonist.

http://www.ncbi.nlm.nih.gov/pubmed/24742134

But may be in the next decade there will be no more warfarin

But in a few weeks it is going to be specific antagonists for them (for example Apixaban) and more will come soon. I think warfarine is taking its last breathe !

http://news.bms.com/press-release/portola-bristol-myers-squibb-and-pfizer-announce-statistically-significant-results-fir

Thank you Joaquin

I think that Warfarin may disappear altogether given that its effect (despite regular anticoagulation monitoring) is not always predictable and only about 40% of patients actually achieve therapeutic target levels! However, it is true that we have a lot to learn about newer oral anticoagulants.

I sure hope not! The behavior of big pharma with the new drugs, saying they do not need to be monitored, is for the  marketers only, not for the real world, in my opinion, You might look at Jelliffe R: Concerning Antiplatelet Therapy. A letter to the editor, Am. J. Cardiol., 2014;113:2086-2087. Be sure to look at the reply. It comes just after. The data must have all been there since Migliorini et al publish both the response (antiplatelet effect) and the outcome. There was NO search to find out WHO bleeds. Or WHO has a bad event. But the data HAS to be there.  It seems to me that NO ONE LOOKED for any relationship between effect and outcome. WHY? Because that goes counter to the advertised marketing strategy of BIG BAD PHARMA! The response (see the figure in the article referred to) ranged from almost none to almost total antiplatelet effect in both the tteatment groups. It seems to me that this is true of the marketing of essentially all the new NOACS. What a great opportunity is missed, as the new drugs may well be better, but no one seeks to optimize the therapy by wanting to monitor the anticoagulant or antiplatelet effect.

The lawyers see the results at both ends of the spectrum, and we see their ads on TV - call 1-800-BAD DRUG. What about 1-800 BAD PHARMA? What about 1-800 DUMB FDA? What about 1-800-POOR DOCS? Big Pharma, it seems to me, preys on the untrained physicians, who generally ask for and get NO OTHER training in how to give drugs except from Big Pharma. What a sad performance of the marketing of these drugs as the recent American Heart Assn meetings in Chicago! I will change my tone, and my anger, when I see a change in the ethical behavior of BIG BAD PHARMA, the poor behavior of DUMB FDA, and that of the POOR, PASSIVE, totally uncurious, UNTRAINED DOCS at the Am. Heart Assn.!

That`s a real good questions!

I agree with all first answers, however I hop not as Roger Jelliffe .

It`s a big world with amazing differences and warfarin is a cheap and effective anticoagulant  .

Thanks to all professors for their answers

Actually we do perform drug monitoring in NOAC, however, not on a regular basis. But if a patient on NOAC therapy is admitted to hospital due to bleeding complications or even the opposite, we are performing drug level tests. However, we are only learning to interprete those values clinically, which could all have been done by the companies which developed those drugs...

We also had a patient who did not have any anticoagulant effect when taking dabigatran (see link). Such things just do not happen if you monitore the effect of anticoagulation.

Finally, although I do not completely aggree to Rogers answer, I think he definately has a point there. Marketing strategies have been rather aggressive when NOACs are concerned.

http://www.ncbi.nlm.nih.gov/pubmed/23782198

Dear Dr. Strobel

     Thanks for your input. Yes, people ARE starting to monitor these drugs and to individualize their dosing. And I think you are correct that essentially all of this could have been done by Big Pharma. They could have seen what is the case in who clots and who bleeds, and the authors of the article I discuss also could have found the antiplatelet effect at which their patients were best positioned with respect to good and adverse responses. This could well be the useful target goal for such antiplatelet dosing. It is truly depressing to see such bad behavior on the part of companies that do such good basic science and go through such significant problems in drug development then come to behave so badly when it comes to marketing the good stuff they have developed. In my view, their behavior here is clearly unethical. Where is the FDA in all this? They approve these huge clinical trials that involve thousands of patients, but they waste the power of their studies by choosing to remain blind to what actually happens between dosage and outcome. Such a waste! Such a waste of money as well! What is wrong with the FDA? Why do they not mandate such monitoring to get the real information necessary for individualized and optimal dosing dosing? Why is it that so many in the FDA go on to be consultants for Big Pharma? Do you think this influences their behavior while they are in the FDA? I believe that the FDA is really the SLAVE of the bog Pharma they are supposed to regulate. Good for all of you who seek to monitor any drug therapy to find out what really happens between dose and outcome, and to seek to optimize it.. Fie on those who don't!

These drugs were admitted to the pharma market without antidots and so we have an extensive field study, now. And patients with complications had and have to pay the bill.

These drugs have to be monitored by a suitable F10a/thrombin generation assay. What is their benefit when compared with the physiologic drug LMWH ?

Not in the near future. As the commenters already said, we don't have adequate monitoring and antidotes for them. Even if these become available (at added cost, to be sure), warfarin might end up as an "orphan drug" or "repurposed" - with an exorbitant price increase....

not yet

The perfect drug, like perfect llove, it does not exist!

NACOs could be a nice drugs, but the practical use could defeat, like it has happened with another drugs. Also, all new NACOs are not equals,

We need RCT to approve the use of new drugs, but observational studies of the "real" world are more neccesaries. The perfect patient selected in the RCT, it does not exist at my real hospital life.

Long life to warfarin (and acenocumarol)

I dont like the fact that there is no antidot. Warfarin is (and probably will be) still my choice.  

I will hold on to warfarin. Despite i have never prescribed the new oral anti coagulants but i have seen and treated many of the victims who were prescribed these serious medications. Bleeding to death or near death is an ordinary and frequent side effect. The transfusion demand for treatment is enormous. There is no justification to move away from the time honored warfarin to the danger zone.

It is amazing how the pharma have promoted these drugs to non hematolgists and suddenly it has become a standard of care for surgical prophylaxis and treatment.

Did any one asked the question why the hematologist is asked to start warfarin and heparin while the NOACs can be started by anyone?

Good for you, Mohammed. I think the problem is that these are really good drugs, but the way they are dosed is the problem - the one size fits all, plus the really strange behavior of the marketers that THEY SAY monitoring is not needed, and because of this, the FDA and the almost the entire medical community thinks this is so. Look at the paper by Migliorini et al in Am. J. Cardiol. 2013;112:1843-1848, and especially in Figure 2 of it. The antiplatelet effect with both Prasugrel and Clopidogrel ranges from 70% residual platelet activity all the way down to zero, for BOTH drugs. The most frequent effect is about 30% for Prasugrel and 45% for Clopidogrel in the actual distributions AT THE DOSES GIVEN (never mentioned in the discussion!), not the assumed normal curve they erect around each set of data. This  extremely great variability in response is the problem. This is why these drugs NEED to be MONITORED with antiplatelet effect and the dosage individualized. Again, the authors MUST have the data, from the figure and their published responses, and be able to  know WHICH patients clot and which ones bleed. But they do not show it! Look at their reply to my letter to the editor of the Am. J. Cardiol. in Am. J. Cardiol 2014;113: 2086-2090. It also reveals the depth of their lack of knowledge of the problem, I believe.

     I was put on clopidogrel after my stents were put in, and if I would take 75 mg/day on top of my aspirin 650- mg.day for my arthritis, I would bleed all over the place. I take the clopidogrel 75 on Mondays, Wednesdays, and Fridays. My assay system is my nuisance bleeding which is not too bad, and the fact that my dermatologist has significantly more trouble taking my basal cell carcinomas off my face when I forget to stop it, and a much better time of it when I do remember to stop it. That is the way I have to monitor my antiplatelet effect. I bet a whole bunch of other patients do something similar, and may not even tell their docs..

     The lawyers see both ends of the spectrum of response and say to call 1-800-BAD-DRUG. They are laughing all the way to the bank, and so is Big Pharma. What is wrong with the medical schools that their education is so bad in this regard? It is because the medical community never kept up with the quantitative advances of pharmacokinetics in the last 50 years, including those in the FDA, which has not ketp up either! So tragic! There are lots of good modelers in the FDA and in Big Bad Pharma, but the marketers hold sway and all you can do today is to call 1-800-BAD-DRUG, worse luck. WHERE IS THE FDA?? waiting for jobs in big pharma?

     These are actually good drugs. It is the way they are marketed and given that is so tragic and evil, in my opinion. One size fits all is NOT the way to give such  meds. Individualized approaches are the way to go. You might look at Jelliffe et al: Human Genetic Variation, Population Pharmacokinetic/Dynamic Models, Bayesian Feedback Control, and Maximally Precise Individualize Drug Dosage Regimens, in Current Pharmacogenomics and Personalized Medicine, 2009, 7: 249-267. I think any clinician who can give coumadin can, in exactly the same way, but probably less frequently, adequately monitor the antiplatelet effect with an assay for it, and simply empirically adjust the dose. Better that than what BIG BAD PHARMA tells us to do now. 

Hi.

Where there is demand for warfarin - this drug will be used.

For example, use of metamizole is usually restricted in developed countries. Metamizole has many accessible alternatives, including aspirin, paracetamol and ibuprofen. But in some countries it is used till now.

At Spain (Western Europe) metamizol is allowed and widely used!

Warfarin is a time tested medicine. Cost is also low. However the problem is routine monitoring of coagulation profile and episodes of bleeding. Newer anticoagulants are safe and effective with less need of monitoring but they are costly when compared to time tested warfarin. Warfarin may become a part of history in developed countries but for developing countries its going to stay.

I do not believe the new ones need less monitoring. I think that is hype from big bad Pharma. Maybe so, but they DO definitely need monitoring and dosage individualization. Look at the previous discussions here. The fixed doses of these drugs give the FULL spectrum of response from almost none to total. There is data in the paper of Migliorini et al, and in my letter to th editor of the AJC about this. The data must be there, as they publish it separately but did not look for the relationship in individual patients. Maybe this only attaches 1 file at a time. I will try to attach the other in the next answer.

The other attachment is hopefully here.

All the best to all.

Roger Jelliffe

Some colleagues and me came across this just yesterday:

Although some studies are experimenting with that, so far the new oral anticoagulants cannot be used in patients with artificial heart valves. They seem to not work properly in that indication...

Too early to tell. Big Pharma has invested heavily on direct to consumer advertising.

I have already seen in my travels bleeding complications related to these agents.No

Big Pharma seems to invest in therapeutics without thinking in the adequate diagnostics.

Too soon!