This is peggy peck recording prayer medpage today from the american heart association scientific sessions in orlando florida in the world of interventional cardiology success means fewer heart attacks and fewer strokes more lives saved that success is often dependent upon the choice of dual antiplatelet therapy currently the standard is aspirin plus cope integral but
Today researchers presented new information about a third-generation drug one that may be better than clopidogrel good morning everyone i’m dan jones i’m the president of the american heart association so let me introduce our first presenter this morning the first trial that you’ll hear about is the triton timmy 38 evaluation of prasugrel compared with clopidogrel
In pci elliott antman those director of the samuel levine cardiac unit at brigham and women’s hospital and professor of medicine at harvard school of medicine in boston will present this dr. edmond thank you very much dr. jones good morning ladies and gentlemen it’s a honor and a privilege for me to present the results of this trial on behalf of the trying to
Me 38 investigators i’ll remind you that the triton timmy 30 at trial was supported by a research grant to the brigham and women’s hospital from daiichi sankyo and eli lilly and company let me set the stage for this trial so that you understand the goals that we had when we embarked upon this project we sought to test whether a regimen that is associated with
Higher degrees of inhibition of platelet aggregation that is inhibits the abilities of platelets to clump more effectively than other regimens would reduce events in patients undergoing percutaneous coronary intervention we also sought to evaluate the safety of that regimen we tested these hypotheses and goals by examining one drug versus another we we asked an
Overarching scientific question which is whether we could come up with a regimen would produce a higher level of inhibition of platelet aggregation that is decreased the ability of platelets to clump together and decrease the ability of a clot to form and if we could identify such a regimen would it be associated with a reduction in events in patients who undergo
Percutaneous coronary intervention and have a stent implanted and the other question would be how safe is it to actually use such a regimen the triton timmy 38 trial enrolled patients who had an acute coronary syndrome unstable angina non-st elevation mi or st elevation mi provided they were moderate to high risk and there was a plan to perform pci all patients
Received aspirin 13,600 patients were estimated to be required to have at least ninety percent power to test the primary hypothesis stratification was used for the randomization so patients were stratified based upon whether they were unstable angina and stemi or stemi and in a double-blind fashion received one of the two regimens shown on this slide clopidogrel
With a loading dose of 300 milligrams or maintenance and followed by a daily maintenance dose of 75 milligrams or a novel finer pyridine krasa grell a loading dose of 60 milligrams 10 milligram maintenance dose i’ll come right to the point here there was evidence of superiority of the procedural regimen over clopidogrel but with the benefit comes a risk in this case
The risk was bleeding hi i’m peggy peckham with medpage today and this is a question for dr. ant-man dr. hammond the results are very impressive but when i look at the the editorial that accompanied the the paper in the new england journal of medicine i just like to quote this one line from the editorial and have you comment on it in triton timmy 38 for each death
From cardiovascular causes prevented by the use of prezi grill as compared with clopidogrel approximately one additional episode of fatal bleeding was caused by prazak and reporting system could you just comment on that because that seems to me to be a bit of a stopper with prasugrel there were 16 more bleeding related deaths with the presser brel and there was
One more death prevented with prancer girl that was not cardiovascular bleeding in nature so the net tally if you like is nine fewer total deaths with pratt’s grill compared with clopidogrel that was not statistically significant what’s important here is that we believe we’ve isolated out where the majority of the excess bleeding is occurring and most of the fatal
Bleeding in this particular study that benefit came with the cost of additional bleeding i think we always need to weigh the risk versus the benefit and the things we dealing medicine so the risk and that’s that you just alluded to the risk is bleeding risk is always bleeding with an antiplatelet agent so what exactly did they see in this trial in terms of leaving
So again with plaza grill compared to clopidogrel the hazard ratio for significant means was about 1.3 to so it’s a thirty percent increase in bleeding with with a plaza grill compared to clopidogrel despite that the overall net clinic clinical benefit which is a combination of how much morbidity was induced by the by the complications of the drugs specifically
Bleeding in this case and the overall benefit with respect to reducing the primary endpoints it was still in favor of placerville there’s there’s always a risk um there’s always a risk and we we have to recognize that to the most the best study drug in medicine is aspen um but we don’t advise that every american adult taken and i don’t take it as a 58 year old man
Because it’s benefit in me it is not sufficient to outweigh the risk and so anytime we add additional agents to the interfere with claudine process we are going to incur some incremental arrest just just one file a brief follow um so going forward and looking at looking down the road in terms of fda approve ability of this drug um would you suggest that this that
This drug these data suggest an approvable drug but with the possibility of a label a warning label on it i would feel uncomfortable giving it to individuals with a prior stroke or transient ischemic attack so the wording that would potentially be used in the label will have to be considered by the regulatory authorities and i believe that we make a fundamental
Error if we begin to toy with the evidence in ways that we think is going to help i think we should use that evidence to base our dosing decisions and our timing of the drug in this case they tested a particular dose i believe that in applying the using the drug clinicians should follow that evidence and use that i do think they should pay we should pay attention
To what that evidence tells us in terms of bleeding risk so for example on the basis of the data being presented here bleeding risk in patients with cerebrovascular disease prepares to balance the benefit that as of this point in time i would argue as a clinician i will use it in those patients because the evidence says there’s no net clinical benefit likewise
I think we as of right now we would be cautious and in its use in elderly patients and in patients under 60 kilograms now obviously given the u.s. epidemic of obesity there aren’t too many people under 60 kilograms but we should be cautious in those patients knowing that there appeared to be a signal in a post-hoc analysis which is hypothesis generating with
Respect to incremental bleeding but in all the other patients in this trial and by my quick count that’s about eighty percent of them that was about abs of the net clinical benefit was clearly substantial and i would say argues for its use how do you answer that criticism as with anything in medicine we have to weigh the benefits and risks there are significant
Benefits here with presso grow it does come with a risk of bleeding we think we’ve isolated out where the bulk of the excess bleeding seems to be occurring if we can modify the maintenance dose in the future and i think we’re going to be able to strike a net clinical benefit balance for even more than the eighty percent of the population as it stands right now and
The sixteen percent who have a neutral net clinical benefit where there’s no reason to say that one is better than the other we should be able to get to a situation where we can take those sixteen percent of patients squarely in favor of massive l3 reduce the maintenance dose if the drug were proved today and let me also add that in my opinion if we could actually
Approve it with a modified dose for those individuals who would benefit from a modified dose to minimize their bleeding risk i would feel comfortable using and in the overwhelming majority of patients well thank you very much doctor my pleasure
Transcribed from video
AHA: Prasugrel Bests Clopidogrel (Plavix) But Questions… By MedPage Today
