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Net Adverse Clinical Event between Ticagrelor versus Clopidogrel in patients with Acute Coronary Syndrome


(Seng Chan You) #1

Dear all,

The new network study is launched to evaluate the efficacy and safety ticagrelor on top of aspirin in patients with acute coronary syndrome compared to clopiodogrel.

Net Adverse Clinical Event between Ticagrelor versus Clopidogrel in patients with Acute Coronary Syndrome

Objective : The goal of this protocols is conducting comparative effectiveness research to establish evidences for benefits and harms of ticagrelor and clopidogrel in patients with acute coronary syndrome through OHDSI network.

Rationale : The 2016 American College of Cardiology / American Heart Association (ACC/AHA) guideline and 2017 European Society of Cardiology (ESC) / European Association for Cardio-Thoracic Surgery (EACTS) guideline recommended to use ticagrelor on top of aspirin in preference to clopidogrel for patients with acute coronary syndrome (ACS) based on the results from randomized clinical trials (RCT). The study of PLATelet inhibition and patient Outcomes (PLATO) demonstrated the ticagrelor reduced the rate of death from vascular causes, myocardial infarction, or death, with an increase in the rate of non-procedural-related bleeding.
Still, the real-world evidence evaluating net clinical benefit of ticagrelor over clopidogrel has been scarce. Furthermore, there is a concern that non-White patients, especially Asians and Black people, might be susceptible to anti-thrombotic therapy because of excessive bleeding risk.In PLATO trial, indeed, Caucasian patients formed most of the enrolled patients, up to 92%. The meta-analysis using RCT of East Asian patients reported that ticagrelor was associated with higher risk of major bleeding without significant lower risk of vascular death, myocardial infarction, or stroke.
Hence, we aimed to conduct comparative effectiveness research to establish real-world evidences for benefits and harms of ticagrelor and clopidogrel in patients with acute coronary syndrome through OHDSI network.

The whole protocol is released at github. This is released at OhdsiStudy repo, too.

We are searching for collaborators to join this network study. Please let me know if you’re interested in joining this study! And please provide any comments or suggestions.


(Ajit Londhe) #2

Looks interesting! As we’ve worked on a similar study in the past, @jweave17 and I are interested in collaborating on this study and can run it for Janssen.


(Ray Chen) #3

Great stuff as always Chan! Happy to collaborate and run it on Columbia data.
Just out of curiosity, do you know if there’s any evidence of increased bleeding with other antiplatelet agents in East Asians as well? Anecdotally, when I was visiting Chinese hospitals in med school and residency, I had cardiologists mention they’re more reluctant to keep patients on DAPT because they felt that East Asians were more likely to bleed on aspirin or clopidogrel (that’s all that was out back then). But I couldn’t find much on that. Have you heard of similar things in Korea? Do you happen to know more about the evidence base for this?
-Ray


(Seng Chan You) #4

Thank you @Ajit_Londhe @rchen for showing interest on this study.

Asian doctors always think that East Asians are much more susceptible to the bleeding risk and resistant to the ischemic risk. So when NOAC came into the market, many doctors hesitated use full dosage of NOAC because of this belief.

Surprisingly, as @rchen said, there is no abundant evidence about this. And the evidences are controversial (https://www.ncbi.nlm.nih.gov/pubmed/17659915 vs. https://www.ncbi.nlm.nih.gov/pubmed/22221945)

So this study actually evaluate this belief (Asians are susceptible to the bleeding more) in real-world practice across the world. And we need to generate more evidence evaluating this belief.


(Matt Spotnitz) #5

Hi Chan,

This sounds like a great idea! May I suggest that you look into differences between coumadin and non-coumadin users, and stratify according to INR? I have found that for non-coumadin users there is an association between INR and post procedure bleeding and mortality. Additionally, there is an association between INR and mortality following an intracranial hemorrhage. Please let me know if you are interested in this kind of subgroup analysis. Also, if you are interested in verifying the models I have run with your data, I would be happy to share my cohorts with you.

Best,

Matt


(Ray Chen) #6

Thanks Chan! What a strange/interesting suspicion all over East Asia :smile:
Not to throw us down too many tangents/rabbit holes, but since it seems like we need more evidence about safety outcomes (and particularly bleeding risk in Asians), should we extend this study to all antiplatelet agents? Or do a separate one that includes all drugs? So that would be all antiplatelets–aspirin (I know we can’t track OTC but for ACS, it’s often full-dose hospital or ED-administered), clopidogrel, prasugrel, ticagrelor, and cangrelor?

And @mattspotnitz, you bring up an interesting point. However, looking back at the original PLATO trial, it seems that they excluded patients on anticoagulation. @SCYou did you want to follow PLATO and exclude patients on anticoagulation as well, or did you intend to keep them in? I don’t see anticoagulation mentioned in your current protocol


(Seng Chan You) #7

I didn’t exclude those with anti-cogulation. But the proportion of anticoagulation will be described in the baseline characteristic table.

@rchen, Yes, we do need more data and evidence for this theme. One of my research project is to evaluate the hemorrhage risk and identify risk factors for hemorrhage in elderlies with atrial fibrillation, who are using anticoagulation including warfarin or NOAC between East Asians and others in the world. Another topic I’m interested in, is real-world practice for PCI patients with AF. Current guideline recommend to use clopidogrel + NOAC and then continue NOAC only. But I don’t think interventionist discontinue the anti-platelet and continue NOAC.


(Hyung Joon Joo) #8

Happy New Year! Recently, Korea University Hospital set up CDM DB!
I would like to join this research. Is there any requirements ?


(Seng Chan You) #9

Thank you for showing interest on this study. @JooHJ

The study protocol and the executable code is released at github

Recently, I revised the code to add several interaction term analyses (eg, old age, women, high aspirin maintenance dose(>=300mg)), which has not been reflected on the protocol document. There are some issues, I need to update further, too.

Still, the package is executable. So you can run the package. If you have any problem while running the package, please let me know.

Happy New Year :slight_smile:


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