Dr. Christopher Granger, Dr. Lars Wallentin, and Dr. C. Michael Gibson present: Results of the ARISTOTLE Trial: Apixaban versus Warfarin in Patients with Atrial Fibrillation.
Chris you just presented the results of aristotle here at the late-breaking trials very exciting largemont you set the stage for us who were these patients what was the disease state yeah i mean this are the usual patient started in nadir fibrillation trial when we embarked on the trial it was really the first time that a big global trial with double-blind treatment
Using double bind warfarin was used so it was a challenge in the design we didn’t know that much about the dosing either there was no phase 2 trial so it was kind of an educated guess to start it so it has been a very exciting a trial to perform of course the patients were those with atrial fibrillation that an increased risk of stroke and they should be a certain
Proportion of warfarin he patients 40% of the patients are really not exposed to warfarin before and then we have 60% that have switched then from warfarin to the new treatment and they were followed for 1.8 years and we really had the big expectations but of course the primary objective was to show that a pixel ban was non inferior as good as warfarin but we
Had three more objectives we we set out to show that it was also superior in stroke reduction stroke prevention in comparison to warfarin and we achieved that and we had as our third target to show that these should be achieved at a lower risk of bleeding and we achieved also that and finally this was translated into a reduction in mortality and even that was
Significantly achieved so it has been a great result even overwhelming result when this soup and we saw them for the first time in june this year and now we have it published presented publicly and open for this guy and i am sure chris who has been presenting the details would like to review some of the details with you well thanks laurie yes it but that’s a great
Summary but there was this 21% relative risk reduction in total stroke and that was mainly driven by a reduction in hemorrhagic stroke there was a 49% relative risk reduction in hemorrhagic stroke but also some reduction in stroke that was ischemic or uncertain type and then there was this very impressive at the same time reducing total strokes a better efficacy
Also this very impressive reduction in bleeding so major bleeding reduced by 31% enormous ly statistically significant and really quite an unexpected finding to have both of those together with one dose both the reduction in stroke and a reduction in bleeding and then perhaps not surprising and i think you’ll put this in perspective of the other trials loras but
When one reduces intracranial hemorrhage not surprising to reduce mortality but it was gratifying to see for the first time really in a in a rigorous prospective fashion looking at looking for a reduction in mortality a statistically significant 11 percent reduction in all cause mortality this also was in the context of a drug that was better tolerated than warfarin
So very well tolerated fewer dis continuations of a fixable than warfarin and and this was also in consistent across all subgroups we had 21 pre specified subgroups and none of them approached statistical significance for the interaction so for the primary outcome so a very consistent effect across geographic region warford naive chad score renal insufficiency all
The important subgroups age for this particular population so as laura says we’re really delighted with these results and and a question that comes up often times then is now we have three trials that are completed and one well four trials that are completed and one ongoing looking at these oral anticoagulants and now what do we make of the whole field and lars
You’re the perfect person to address this having led two of these trials yeah i think one is here that can be emphasized it is that we are comparing to warfarin and the quality of whorfin treatment is variable between different countries between sites and we are today also presenting the results in relation to quality of warfarin treatment in relation to time in
Treatment range and the time in treatment range in at a median in there is total trial was 66% and that’s rather comparable to what was achieving the open label rely trial and it is comparable to what has been achieved in previous atrial fibrillation trial i think the quality of care in the warfarin arm was rather high it was higher than in the rocket trial that
And with another tane inhibitor recently presented so we are proud about that and unhappy and and when i present the comparison in relation to centers iron ore control it turned out that we have really no significant differences in you compare a pizza ban and warfarin incentive with more pure iron ore control and also in those with better in our control we have
Consistent results so i think this is one advantage of this trial that we really had have good documentation that irrespective of time in treatment range we see these benefits of a pixie ban there was somewhat less of this consistency with the bigger trend where it seemed that concerning mortality and reading there were more of an effect in centers if who are in
Our controls of course the comparator here is always important if i think another advantage of a pixie ban is the safety because this is a prophylactic treatment patients with afib and an increased risk of stroke they don’t have many symptoms and we don’t like the treatment to create symptoms so we had with a pixie ban a substantial reduction in gastrointestinal
Bleeding and that is in contrast what was seen you big around that increased the risk of gastrointestinal bleeding and the same was seen as a matter of fact with rivaroxaban in the raca tribe so it was definitely safer there have been a lot of discussion about a signal of increase in my cord limb function seen with oral trombone inhibitors like the bigotry and with
A fixer ban there was definitely no such signal there was a slightly less my calling functions not significantly so but definitely no signal of an increased risk and overall there was no safety issues that we have been seen no differences in any adverse events no liver signal and so therefore i think that really physicians can be very confident if you’re comfortable
And starting a patient on a pixie bond that they now have a convenient safe and also more effective treatment of warfarin so i that kind of summary that i i think there is an edge to apixaban concerning safety and with about the same efficacy as the previous best new compound the big attract so as i said this really was a typical population very similar to rely
Lawrence wasn’t it that the mean chatter was 2.1 without a third of these patients were jed score of one a third were chatsworth two and a third were three or greater so this really does cover the entire spectrum and loras another question that’s come up is given the results of rely rocket aristotle will there be a shift do you think in in what we believe should
Happen with patients who were chad’s one yeah i would think so and we were in looking into patient with chad’s one with the bigger tram versus warfarin the effect seemed relatively even larger in that group and i think we it’s very consistent with what we see will apixaban that we have a striking effect in chad’s one so i aspirin is definitely no alternative and we
Need to remember that we have the hemorrhoids trial comparing a picture ban to aspirin and seeing a dramatic reduction in stroke and so therefore i would say that aspirin is definitely no first choice any longer any patients with afib and any increased risk of stroke maybe we will come down to shed zero but that’s more doubtful and that has never been tested in the
United states one of the barriers that we’ve got and i think worldwide is cost new agents are quite expensive so another thing we’re hopeful for is now that there now that we anticipate that there will be more drugs on the market that maybe there will be some downward pressure on cost because these results are so important i think for patient care that that it’s
It’s a shame if we have some of these barriers to patients getting the benefits from the drugs such as such as very high cost and i think if there was no cost issue i mean warfarin would definitely leave the market immediately and no one would start any patients on warfarin why should they they have a more convenient safer and better treatment so i think cost is
The only issue and we really hope that maybe the if medication is more cheaper maybe the companies might gain even more by having more patients treated with it we know do the back of the envelope analysis of the cost-effectiveness of daddy when you have presented your results and when you have the kind of mortality reduction you had you’d have to treat about 200
Patients and i think the societal cost of that was about 10 or 20 thousand dollars a year that person goes on to live about six years after the any event so it ended up being about $30,000 per year who i saved and that does seem to be kind of in the mid of cost effectiveness data but of course the nice committee pushed back a bit i think there’s a lot of debate
About the cost of or for monitoring and you know it’s not just the cost of sending the lab tests out i mean there’s the cost of nurses and doctors and the cost of people not showing up and all these analyses discount the cost of a patient losing time from work and coming in and traveling etc so i thought that will have a very thoughtful approach to analyze what the
True cost no i think you need to bring into this also the cost for a care of strokes the cost for taken care of bleeding i mean that would be the reduction in cost for bleeding and and yeah and i mean these analyzers cannot be done in a double-blind trial where all the pigs and patients need to come back for iron or controls etc and maybe we should also take into
Consideration that more patients will tolerate the treatment like a pig’s about in comparison to warfarin there are many patients topping warfarin because of the inconvenience of the treatment because of the side effects if you get more a few patients protected then maybe there is even a gain of using it picks about because you have less strokes in the society and
That’s a very large cost associated with stroke well when your stroke is about $4,000 cost the united states and the major clades about five to ten thousand dollar cost and when you factored that in that number comes down to about sixteen thousand dollars through your wife’s age so yes we really are cutting down medical cost by reducing stroke and reducing major
Bleeding well guys congratulations wonderful work you know i still wonder we really have reduce bleeding and we really have a safety signal here do we really have an advocacy signal we reduced ischemic events so maybe less i could finish with just the the number of events prevented per thousand patients treated so what we saw was per thousand patients over this 1
Point 8 year period there was six strokes prevented four of those were intracranial hemorrhage but two were either ischemic or uncertain type of stroke then there were 15 major bleeding events prevented and eight deaths prevented mortality is very you know death is very common in this elderly afib population and that’s eight deaths that exceeds the number of ic h
That’s correct so i mean when starting out to these a theof trials no one imagined that we really should be better than warfarin and and and there is a reduction in stroke and there is a nominal reduction in ischemic stroke and and i think i will not switch to a prevent one more ischemic stroke to loose on the bleeding side i think the safety side is so important
When you perceive a the patients to take medication that the patient doesn’t even believe that he needs so i think the gains in bleeding is really the one of the big things with apixaban in relation to other to have the best of both dosages of the bigoted ron that’s that’s how we see it so you get the benefit in stroke and over the height of sort of a get run and
You get the benefit of reduction in reading and even more reduction in reading time with a low dose of the bigot ron and it’s a little bit unbelievable that we have a treatment that provides these benefit and maybe we should remember that the verse strokes or the hemorrhagic strokes much worse than an ischemic stroke can be a preventing the worst room you know
Position at that time was hippocrates and one of those things was do no harm and you’re actually doing less harm here with this trial well guys congratulations excellent work thanks for joining us today and thanks to all of you for joining us here at duke tv couple tourism
Transcribed from video
Results of the ARISTOTLE Trial: Apixaban versus Warfarin in Patients with Atrial Fibrillation. By clinicaltrialresult5
