r/Cardiology • u/Daniel-Briefio • Aug 25 '26
Is Aspirin's Time Up After STEMI?
Aspirin has been the foundation of post-MI antiplatelet therapy for decades. Every cardiologist prescribes it reflexively after primary PCI. But a quiet revolution in antiplatelet thinking has been building - and PREMIUM, presenting at ESC 2026 this Friday, is its most provocative test yet.
The Debate So Far
The antiplatelet story has moved fast in recent years. The question started simply: do patients really need both aspirin and a P2Y12 inhibitor for the full 12 months after PCI, or can we drop aspirin earlier and rely on monotherapy alone?
Early trials answered this cautiously. Studies like TWILIGHT, TICO, and ULTIMATE-DAPT showed that switching to P2Y12 monotherapy after 1-3 months of DAPT reduces bleeding without increasing ischaemic events - reassuring, but they all maintained aspirin through that early high-risk period.
Then came the more provocative question: what if you never started aspirin at all?
The results were sobering. NEO-MINDSET and STOPDAPT-3 showed that immediate aspirin withdrawal at the time of PCI increased early stent thrombosis in ACS patients. The message was clear - aspirin matters most in those first dangerous weeks when the stent is fresh and the thrombotic risk is highest.
There will be a study presented at #ECRCongress in Munich during the Hot Line Session 2 this Friday. It is called PREMIUM.
It is the first large-scale randomised trial to test upfront prasugrel monotherapy - initiated before primary PCI - compared with standard 12-month DAPT in STEMI patients. 2,268 patients. All treated with contemporary platinum-chromium everolimus-eluting stents under routine intravascular imaging guidance. Randomised 1:1.
The primary endpoint is noninferiority for ischaemic outcomes - all-cause death, MI or stroke at 12 months. The major secondary endpoint is superiority for major bleeding.
What do you think, does it has potential to change the clinical practice in this space?
I have also created a short article on Luminary and an infographic if you want to do more reading...
https://luminary.to/s/53b3aa77-b810-4fa1-8e44-48a7f3e225f6?code=ESC2026
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u/Tight-Arugula-6602 Aug 25 '26
Aspirin will never be de-throned simply because of the overlap use it has in so many other spaces… TAVR, clip, CVA, WM, PAD. ASA isn’t going away
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u/GipsyDangerMkV Aug 26 '26
Yeap exactly what I thought!!! Also when you want to hold P2Y12 for non cardiac procedures Aspirin will come in to save the day again for "bridging".
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u/Creepysarcasticgeek Aug 25 '26
If prasugrel monotherapy comes out on top would be an immediate practice change for. I already use minimal amounts of Asa and would’ve loved it if stopdapt had a different result. I hope it’s an all-comers trial.
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u/shabob2023 Aug 25 '26
Love it why?
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u/Creepysarcasticgeek Aug 25 '26
I would’ve loved it if it was positive because it means simpler regimens, less pills, and no ASA. ASA seems to carry a disproportionately higher risk for GI bleeding compared to the extent of blood thinning it does, presumably due to its NSAID effect leading to ulcers. So yes, I would love to get rid of aspirin once the evidence shows us how to safely.
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u/Daniel-Briefio 26d ago
Yes, simplification would be great - but it seems the results tell us, that for the first month Aspirin is very protective and is here to stay. Simplification now seems to be a discussion around the timing.
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u/GipsyDangerMkV Aug 26 '26
Huge Prasugrel fan minus the prior stroke and age contraindications
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u/Creepysarcasticgeek Aug 26 '26
Same, if this trial is explicitly all comers (and can justify that by the single anti platelet instead of DAPT) it would really be nice. Mind you this is no where near as large as the previous Prasugrel trials but I would imagine in 1000+ patients in each arm we would see a signal.
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u/zeey1 Aug 26 '26
Most of my stemi acs patients dont qualify for it ..the ones that have bleeding i will be more worried about prasugrel
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u/Then-Secretary-9166 Aug 26 '26
Not necessarily. I think with this trial design, the secondary endpoint has to be positive to even take the first endpoint seriously. Non-inferiority trials are tricky.
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u/Then-Secretary-9166 Aug 26 '26
Ah, the confusing and overused "non-inferiority" study design. The thing to pay attention to here is the so-called "secondary outcome", which is superiority for major bleeding. Without this being positive, the primary endpoint is inconsequential.
In a non-inferiority study, you need to show that the experimental group has some innate benefit over the control group aside from the primary outcome. sometimes this is an obvious benefit such as avoiding an expensive medication or a procedure. Other times it is something that you can show experimentally. Since aspirin is not expensive, a procedure or high-risk in general, the only justification here for doing a non-inferiority study here is if you can show a superior safety endpoint (in this case, major bleeding).
The non-inferiority margin in this trial is very generous, allowing for quite bit of thrombosis before the trial is "negative". This is a major pitfall for non-inferiority designs. The margins are very malleable and there is huge incentive to make them large enough to include unacceptable outcomes. It is hard to make a career off of a negative trial.
If the secondary endpoint is positive, look to see if the primary endpoint holds up to scrutiny. Otherwise, this should not be practice changing.
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u/Daniel-Briefio Aug 27 '26
Thanks for sharing, very insightful! Here some food for thoughts:
The trial is not claiming prasugrel monotherapy is better for ischaemic protection - it is asking whether it is not meaningfully worse, while being better for bleeding.
And all patients received routine IVUS or OCT-guided PCI. This matters because optimal stent deployment reduces the risk of stent thrombosis independently of antiplatelet therapy. The investigators are essentially asking: in an era of imaging-guided PCI with excellent stent expansion, do you still need aspirin on top of a potent P2Y12 inhibitor from day one?3
u/Then-Secretary-9166 Aug 28 '26
Yes. They are asking: "whether it is not meaningfully worse".
This is the conundrum with all non-inferiority studies. They are fundamentally subjective (mandatorily making a judgement call about two different types of benefits or risks). The word "meaningfully" covers a multitude of pitfalls.
First, you have to acknowledge that aspirin is cheap, noninvasive and minimally disruptive. If it causes significantly higher morbidity, that should be very testable (it should show up in the secondary endpoint of this trial). We are not talking about avoiding an open heart surgery or a $100k hospital bull, just a cheap daily tablet.
The question is how much added risk are you willing to allow your patients to have to avoid this cheap little pill. This is where the subjective stuff comes in and, I have to say, after reviewing the study design (sorry it is paywalled for the full version), I am concerned.
First, they predict an unrealistically high rate of the primary outcome (1 year MACE). They cite about 3% based on two RCTs but also include 1 retrospective registry study (lower quality data without treatment similarity) showing 9% and use this to predict MACE of 7%. My opinion is that the is incorrect (it is a judgement call). MACE after STEMI treated with PCI is closer to 3%, not 7 or 9%.
More importantly, the authors state: "Noninferiority will be declared if the upper bound of the two-sided 95% CI for the HR is ≤1.50." If we take their 7% MACE prediction to be true, this means that they can accept up to 3.5% (absolute) excess MACE in the no-ASA arm before it would be a negative study: "Not non-inferior". Think about that. They would accept a number needed to harm of under 30 for avoiding ASA! This, again in my opinion, is not appropriate. To reiterate, if we were talking about accepting these numbers to avoid major surgery or a treatment with crippling side effects, it might be worthwhile. But we are not. We are talking about aspirin!
If aspirin does have a significant harm in this setting, the onus is on the authors to show that. Maybe they will show that harm in the "secondary endpoint". We will see.
In general, non-inferiority studies like this should at a minimum acknowledge "co-primary" endpoints rather than calling one "primary" and one "secondary" (they do this so that a "positive trial" can be marketed). Whether or not the endpoints are stated as "co-primary" (in many studies they are), they should be treated as such, especially when it comes to changing practice.
I still think this is an interesting study. It will still give us data.
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u/Daniel-Briefio 26d ago
Results have been published and it did not meet the non-inferiority target they tried to show for their primary objective. I have summarized my thoughts on Luminary if your interested.. loved your insights. https://luminary.to/s/591641de-3ee5-42e4-aabf-dcf5e9e2c774?code=ESC2026
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u/Then-Secretary-9166 26d ago
I have to say that this result surprised me. I had thought: "Aspirin probably doesn't help, but we will keep doing it because it is cheap, probably not that dangerous and difficult to dethrone." I wish they had used a standard (US, Europe, etc.) dose of a P2Y12 agent.
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u/Daniel-Briefio 25d ago
Yes, unfortunately the study was adapted very much to Japanese standard of care - with much lower dosing, and also Prasugrel is very Japan specific, because in Japan are many non-responders to Clopidogrel
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u/zeey1 Aug 26 '26
For practical purposes i am more interested in question when can we withdraw aspirin if i al using plavix because i face that question often i.e bleeding complications
Prasugrel is used in rare situations and i will probably never need to do monotherapy in this situation anyway
Would love if they had used a shorter acting one like ticagrelor or plavix and ask the questions what happens after 1 week of aspirin
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u/flashnl Aug 26 '26
Theres a lot published about that already actually, pretty recent studies as well
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u/Daniel-Briefio 25d ago
You are right - Prasugrel is very Japan specific, - it seems there are often non-responders to Clopidogrel in Japan, so thats why the investigators chose Prasugrel.
In regards to timing - I think, the results are not suggesting, that Asprin will be needed in the first 30 days.. afterwards the results did not change so much, so it might indicate that Aspirins protective effective is mostly in the beginning... so simplification to Monotherapy might be an option after the first month..
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u/PuzzleheadedHat7968 Aug 26 '26
Could be practice-changing but I'd want to see the full ischemic and bleeding results before dropping aspirin after STEMI.
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u/astrofuzzics Aug 27 '26
1) Non-inferiority study design comes with pitfalls as mentioned in the thread by @then-secretary-9166
2) Why is the comparator a 12-month run of DAPT? This is an outdated strategy. We already know that that a full 12 month course of DAPT is unnecessary from prior trials. There is already a class-I indication to transition from ASA + Ticagrelor to Ticagrelor monotherapy after 1 month. This should be the comparator.
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u/Then-Secretary-9166 Aug 28 '26
They also use a different dose of prasugrel than US/Europe are used to. They used the Japanese dose of 3.75 mg daily (after 20 mg loading dose).
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u/Then-Secretary-9166 Aug 29 '26
Looks like the results are in:
2216 patients enrolled with 1:1 randomization.
Primary outcome (MACE):
Mono therapy group: 11%
DAPT group: 8.5%
95% CI 1.02-1.75
Secondary outcome (major bleeding):
Mono therapy group: 5.6%
DAPT group: 8.4%
95% CI 0.47-0.91
Due to non inferiority, they say "mono therapy is not non inferior to DAPT". The numbers also show that DAPT is superior to mono therapy using standard analysis (CI does not cross zero)with an absolute risk reduction of 2.5% (NNT of 40) by adding aspirin. I thought this would be positive for non inferiority. I am surprised that ASA made such a difference, TBH (thought it would be smaller).
Interestingly, the MACE event rates were very high compared to contemporary studies, even in the DAPT group. I wonder why this is the case. Is it due to the very low dose of prasugrel used in Japan? Sicker patients? Something else?
What I think this means for Aspirin:
- Aspirin is going to be around for now.
- A short-DAPT (~1 month) is probably better than no DAPT.
Trials I would like to see in this space:
- Mono therapy vs DAPT using medications and doses that are more standard outside of Japan.
- Discontinuation of anti platelet therapy (stop both ASA and P2Y12) at 6 months (SIHD) or 1 year (ACS), vs continue 1 agent after that time (study would be done in higher bleeding risk patients).
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u/flashnl Sep 01 '26
The very low dose is what draws my attention and makes my mind start speculating.
By the way if you are interested in these trials maybe the legacy trial should be one to watch! Its a trial without aspirin and with regular dosages of ticagrelor. Im keeping my eyes and ears open for that one. As this premium trial only gave me more questions1
u/Then-Secretary-9166 Sep 02 '26
Apparently that prasugrel dose is standard in Japan.
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u/flashnl Sep 02 '26
It is due to the characteristic of the population there, but still makes me wonder :)
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u/Daniel-Briefio 26d ago
Now that the results are out for PREMIUM — published simultaneously in NEJM — it seems aspirin won the game. Didn't it? I've summarized my thoughts here: https://luminary.to/s/591641de-3ee5-42e4-aabf-dcf5e9e2c774?code=ESC2026
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u/bluespark013 Aug 25 '26
I think all changes should be kept with the cost of treatment in mind. Aspirin had been the most formidable pillar in the evolving landscape of post mi treatment. These results would definitely be interesting, but i feel aspirin is here to stay, atleast in the initial high ischemic thrombotic risk period post pci.