March 24, 2023

San Diego, CA (May 8, 2015) — Dr. Usman Baber and Dr. C. Michael Gibson discuss Dr. Baber’s Late-Breaking Clinical Trial, “90 Day Effectiveness and Safety of Prasugrel vs. Clopidogrel as Used in Clinical Practice in Patients with ACS Undergoing PCI: Initial Findings from the PROMETHEUS Study”.

Mike gibson a newsman bob are here from sky 2015 this one you just presented the results of the prometheus study tell us a little bit about what the question was you’re trying to answer and the design of the trial well thanks dr. gibson the prometheus study is basically a study looking at real-world patients those patients who are not usually enrolled in clinical

Trials and trying to understand in a real world context how is press a real being used what are the determinants of prasugrel use and also what’s the safety and efficacy profile of prasugrel as compared to press priscilla’s compared to clopidogrel sure and that was the basic fundamental question we were trying to ask with with this study and how many centers did you

Have what was the scope so what we ended up doing actually is we use a little bit of a novel approach to conduct this study we went to different medical centers across the united states we found 8 centers each of these centers maintains our own database on patients who come in with acute coronary syndromes get treated with clopidogrel or procedural and these centers

Provided us data on their patients between 2010 2013 and in total in this manner we were able to generate a data set of 19 thousand nine hundred and fourteen patients all of whom were treated with either co peterborough prasugrel underwent pci with stent implantation all those data were then sent to us at mount sinai where we aggregated harmonized and generated

One unified patient level pool dataset and the primary endpoint of this analysis was the rate of mace which was defined as death mi unplanned reeve ask or stroke at 90 days from the time of pci and how about the quality how confident are you of your ability to ascertain events from this kind of electronic medical record or database yes i great great question the

Method that we use to obtain these data certainly has certain advantages and disadvantages the advantage is that it was very efficient we were able to leverage the existing resources that existed at all the academic medical centers and allowed us to construct a dataset within a very short time frame less than 12 months we were able to put these data together by the

Same token we had to rely on the quality of the data that existed sites therefore for example if sites did not routinely do social security death index searches for example we weren’t able to go back and get that information so there were certainly certain advantages and disadvantages and we try to do our best to minimize any of the biases that can occur in this

Kind of analysis and study design so did they search for you know icd-9 codes or something to say someone have been rihana lies but what if they got riha sliced up side their system how do you know they hit an event so in general most of these centers collect data on their patients after pci through multitude of mechanisms these might be through routine patient

Phone calls these might be to return visits primarily at their own site it may be so this is more than your usual hospital kind of yeah database tracking whether they were readmitted exactly we did not this was not based on icd-9 codes based on what they had available to them at their at their centers and i can tell you that based on we assumed we were going to get

Am a straight of about eight percent or so mid 90 days and i certainly think we did collect a reasonable number of events because our may straight actual a little bit higher than that at 90 days so i do think we were able to collect events but certainly caution has to be taken in terms of miss classification of events and and and and again ascertain meant bias in

Any kind of retrospectives that the lesson is always is that the event rates in the real world always higher exactly randomized trials are exactly correct and how about any kind of comparisons between capita grow and press a girl absolutely so what we found is that at 90 days the unadjusted benefit favored prasugrel in by about forty two percent relative reduction

In mace in other words the procedural treated patients had a substantial benefit compared to the comparable treated counterparts now it’s also important to point out that what we found is that the profile these were probably younger patients exaggerations as i was right in terms of in terms of what we found he noted number one that the overall use of prosecco so

Only one out of five patients and this 19,000 our patient data set actually received password all the time of pci it’s only twenty percent in terms of hit excluded people with prior stroke court eia and exactly they had excluded the little old ladies who are 75 kilograms and you’re exactly right and the patient profiles were remarkably different the patients who

Ended up receiving prosecco in this data set were much healthier they were younger less diabetes less renal disease less anemia compared to anybody’s that’s odd because really that’s a sweet spot for press grow it is and i think one of the insights from the prometheus study is that it allows us to help better understand what influences therapeutic decision making

At the time of pci and you’re absolutely right a traditional classical marker of risk such as diabetes mellitus was actually less common in the practical treated patients suggesting perhaps that what’s driving us to make decisions may be more driven by concerns about therapeutic toxicity in terms of bleeding rather than therapeutic benefit but we can’t say that

The way press grow is being used in the real world is effective doctors are selecting patients in an appropriate way and having good outcomes yes and i think i certainly believe that are that the study does suggest that again we found at 90 days the unadjusted benefit was very large in favor of prasugrel now we had to do a lot of methods account for the baseline

Differences the primary method we used for adjustment was propensity stratification we did in multiple other methods including inverse probability weighting and other other approaches we found that after you adjusted the benefit was an eleven percent reduction in mesa at 90 days in favor procedural with the non significant p value of 0.17 we and that was similar

For for myocardial infarction as well there was a large unadjusted benefit prasugrel when we adjusted it was attenuated to about a fifteen percent reduction that was non-significant interestingly for bleeding we found again the healthier procedural patients bled less unadjusted when you adjust it however the hazard ratio was essentially 1.0 right on the line of

Unity so in aggregate the findings suggest that the way we’re using a girl in this real world context is in such a manner that the benefit on the ischemic site is modest it’s attenuated not at the level we see in triton timmy 38 nevertheless we are also not exposing patients perhaps that same level of harm well we looked within triton we did find that if you get

Rid of the people over 75 get rid of the little old ladies if you get rid of the powerstroke ti that population of people about the eighty percent that remained didn’t have really that much excess bleeding that sounds like this real world look mimics that kind of announces yes and i think in many respects our findings are concordance with the prospective translate

Ecs registry wherein they also demonstrated large unadjusted benefits and then when you adjust it away the differences the benefits were minimized and attenuated and i think we’re seeing in many regards as similar some we’re finding with with the prometheus study excellent well congratulations ninety thousand patients thank you nineteen ninety thousand nineteen

Thousand still lot of patience a lot of patience a lot of work and it was and then it was a pleasure to be be here have an opportunity presented yeah but did a great job thank you so much thank you and thanks to all of you for joining us here live from sky 2015

Transcribed from video
SCAI 2015: 90 Day Effectiveness and Safety of Prasugrel vs. Clopidogrel By SCAI-TV