Fair review of the data and I agree, it is insulting when the only answer seems to be no head to head trials:

My view is how did ARISTOTLE achieve a lower mortality while not reducing stroke to the extent in RE_LY? I think the answer is the reduction in major bleeding. It has long been known in ACS trials that bleeding is associated with worse outcomes e.g. TRITON timi 38 caused a fatal bleed for every case of CV death prevented. We have always been happy with the efficacy of warfarin but worried about its bleeding profile. So ARISTOTLE gives us better efficacy and a very impressive safety profile. AVERROES before that confirms this safety, which is comparable to aspirin. 

Nice wrap-up of these recent trials.

I practice in Belgium, where we don't have (and probably won't for the next year at least) available any of these newer drugs within the reimbursement system. In practice this means that patients will be very reluctant to swichts to or start up with these (in comparison) very expensive drugs.

There is one trial I keep missing in these discussions or comparisons, which is the PROTECT-AF trial> comparing warfarin to LAA occlusion with the Watchman device.

 When comparing costs in my local setting, this matches well with the newer drugs...

Try comparing PROTECT-AF with RELY:

CHADS 2.2 vs 2.1

Time in therapeutic range 66% vs 64%

RRR dabi 110 vs warfarin  0.91

RRR dabi150 vs warfarin  0.66

Watchman vs warfarin 0.71

 discontinuation rate RELY 20% - - - compare to 87% succesful implant

dabigatran 1 dose bid  >< Watchman once ever

Cost dabigatran about $3000/yr   -- warfarin $ 100/yr --- watchman $ 5000 once a lifetime

I think new device therapies should be added to the equasion, we might be surprised 

Dr, Seth, if you would have noticed, the efficacy benefit in the ARISTOTlE trial for apixaban in the EU subgroup and patients < 65 years was muted. In the EU subgroup, the both apixaban and warfarin were associated with a 1% event rate, while in patients < 65years the stroke rate was higher in apixaban compared to warfarin ( 1% vs. 0.9%).

regards

Vishal 

Dr. Bilazarian:

 Thanks for your insight into these new anticoagulants.  One of the factors that may increase prescribing for the Factor Xa Inhibitors is the availability of an antidote.  Currently there is an antidote for Factor Xa about to enter Phase II clinical trials.  I am unaware of any antidote in the pipeline for the direct thrombin inhibitors.

Roger

Data from ARISTOTLE is in fact really impresive. Does anybody know the reasons for the 25% of discontinuation the drug ? Also, what were the distinct characteristics of the population in whon half a dose was uused ?

Thank you 

I'm from the noth of Argentina

The quetions is ¿ Are there real benefics ? or we can use any one

Please understand me, the cost-benefits  is the most

Thank you to all participants, is really good theis Foro

Sergio hauad

Professor of Cardiology

Tucumán Universirty

Argentina

You should always remember that "theheart.org" is no charity. It makes money and that why it is always (almost) pushing what is "new", "modern" and more expensive. Pharmaceutical industry is more interested in giving them so called "unrestricted grants" if the play the game.

Now suddenly atrial fibrillation is a big issue. You should remember that if you work in Canada, the US or western Europe the average quality of treatement with warfarin (measured as time in therapeutic range, INR 2,0-3,0) is much better than the averages in the three trials, around 60-65% whereas in my country Sweden the average in clinical practice (not trials) is 76%. It goes without saying that the results for the warfarin patients is much better if time in therapeutic range is 76 % than if is is only 40% as it is in some of the trial countries. The better results for the new drugs regarding intracranial hemorrages I am aware of.

Nothing said about the lack of antidotes in this "cliical corner"! In a case with major bleeding we can reverse the anticoagulation with vitamin K (warfarin), what do we do with the new drugs??

I read the heart.org as it give me NEWS, but I try to remember that theheart.org works under the conditions the industry gives them, so keep your critical eyes open and do notice what is overemphazised and what is left out in the information. It is not by chance...

Anders Hernborg MD
Swedish GP in our local Drugs&Theraputics Committee
(lets see if this msg is removed as having "personal agenda" or "hostile intent"!?) 

When will we see a risk/benefit examination that considers the iatrogenic potential of warfarin in promoting arterial calcification and aortic valve calcification?  Ostreoporosis? When will we see a discussion of the differences between vitamin k-1 and vitamin k-2 relevant to the beneficial control of mineralization (enhanced in bone, prevented in soft tissues) vs. pathological outcomes due to suppression of M-4 and M-7?

[No professional or commercial conflicts of interest.]

The Swedish experience cannot be generalized to North America or the rest of the world. Sweden has very high life expectancy, highly compliant patients and has been using warfarin in the aftermath of MI and stroke for many, many years (since the 1960's).  Our health care systems are much more scattershot and diffuse and our TTR's are consequently much lower.  Just do a shift in a busy emergency department if you want to see a cardioembolic stroke (devastating) due to an under-anticoagulated patient or a hemorrhagic stroke (devestating) due an over-anticoagulated patient.  I just saw a patient in whom warfarin was stopped because it was too difficult to manage her INR - she ended up with a devastating and paralyzing stroke.

 Here we have drugs that compared to warfarin reduce rates of ischemic stroke, mortality and major hemorrhage.  They require no monitoring, have few drug interactions and can be consumed with green leafy vegetables.  In the end they will be highly cost-effective. 

I absolutely agree with my swidish collegue dr Anders Hernborg - be critical for news, be logical in your therapeutic decision and base on Your own practice and expiriences.