12-05-2025
Is a Year of DAPT Magical Thinking?
Christopher Labos, MDCM, MSc
It's hard to accept that babies born in the year 2000 now have kids of their own. It's even harder to accept that there never was much evidence for 12 months of dual antiplatelet therapy (DAPT) after coronary stenting.
In a recent commentary, lead author Marco Valgimigli, MD, PhD, likened the routine use of 1 year of DAPT to a myth that has become entrenched in our collective culture. Though recent trials suggest shorter durations are feasible and possibly better, untangling truth from myth is proving to be a Gordian knot.
Enter the DAPT Era
The era of DAPT began with the publication of the CURE study in 2001. Patients with non-ST elevation myocardial infarction were randomized to aspirin plus clopidogrel or aspirin plus placebo. Despite the increased bleeding seen with the addition of clopidogrel, the trial's positive primary outcome prompted many, myself included, to start putting patients on both drugs.
As more potent anti-platelets such as prasugrel and ticagrelor came to market, on the basis of TRITON-TIMI 38 and PLATO , respectively, the idea of yearlong double therapy was reinforced. But in TRITON-TIMI 38, median treatment duration was 14.5 months and in PLATO it was just over 9 months. Neither study provided 12 months of DAPT nor tested a specific duration of therapy.
The subject grew more complicated as the field evolved. Bare metal stents improved and then gave way to drug eluting stents which in turn evolved to newer iterations with better scaffolds, polymers, and anti-proliferative agents. In the early 2000's, the risk of stent thrombosis with the first generation of drug-eluting stents prompted a science advisory stressing the importance of 12 months of DAPT. Even though the risk of late stent thrombosis is much reduced with the newer generation of drug eluting stents, a confluence of factors made 12 months of DAPT the standard of care.
But a blanket 1-year recommendation ignores the past quarter century's dizzying evolution in stents, angiography techniques, and background medical therapy. We can justifiably question if studies from 20 or even 10 years ago are still relevant and if the particular risk and medication profile of the patient sitting in front of you has been adequately represented in the clinical trials.
Balancing Ischemic Benefit and Bleeding Risk
Multiple trials have tested alternatives to 12 months of DAPT. The DAPT trial tested 12 months vs 30 months of DAPT and found fewer stent thromboses and cardiovascular events with longer treatment but at the cost of more bleeding. This trade-off has been replicated many times and a meta-analysis of five trials of longer term DAPT showed that extending treatment beyond 12 months reduced cardiovascular events but resulted in more bleeds.
This balance between cardiovascular benefit and bleeding risk prompted the question of shorter durations than 12 months. A summary of this body of evidence suggests that 3-6 months had no major impact on either stent thrombosis and paradoxically bleeding risk compared with 12 months.
While those de-escalation trials usually left patients on aspirin alone, an alternative would be to stop the aspirin and leave them on a P2Y12 inhibitor.
Multiple trials have tested a variety of permutations. The SMART-CHOICE trial de-escalated to clopidogrel in most patients after 3 months of DAPT, STOPDAPT-2 de-escalated to clopidogrel after 1 month of DAPT, while TWILIGHT tested ticagrelor monotherapy after 3 months of DAPT in a high-risk population. Keeping this heterogeneity in mind, meta-analyzing these trials suggests that ticagrelor alone after 1-3 months of DAPT reduces the bleeding risk without increasing cardiovascular events. Whether we can say the same for prasugrel is less clear. The STOPDAPT-3 trial tried an 'aspirin free' strategy with prasugrel monotherapy at 3.75 mg daily rather than the standard 10 mg dose. This strategy did not improve bleeding rates or worsen the primary endpoint, suggesting that prasugrel monotherapy may be feasible. But the atypical dosing and general unpopularity of prasugrel does make it a challenging trial to put into practice.
But Wait There's More De-escalation Trials
At the recent American College of Cardiology scientific sessions in Chicago, there were even more data to add to the mix. The HOST-BR trial tested two different regimens based on the patient's bleeding risk. High risk patients were randomized to 1 vs 3 months of DAPT and low risk patients were randomized to 3 vs 12 months, with clopidogrel being the most common second anti-platelet. In high bleeding risk patients, limiting DAPT to 1 month increased major adverse cardiac and cerebral events (MAACE) at 1 year by 4.0% on the absolute scale with a non-significant trend towards less bleeding. By contrast, in the low-bleeding-risk patients, limiting DAPT to 3 months instead of 1 year had no major effect on MAACE but reduced bleeding by 9.5% on the absolute scale. In both the high and low risk patients, 3 months of DAPT seemed to be the sweet spot.
SMART-CHOICE 3 took a different tack and evaluated patients that had already completed their 'standard' duration DAPT (12 months post myocardial infarction and 6 months overwise) and randomized them to monotherapy with aspirin vs clopidogrel. At 3 years, clopidogrel reduced MAACE by 2.2% with no effect on bleeding.
Both of these Korean trials were open label studies. In East Asian populations, differences in bleeding risk suggest that clopidogrel might be superior to ticagrelor, hence the decision to use it in the study. However, in other ethnic groups the same might not hold true, and whether the results would replicate with ticagrelor is anyone's guess.
Guidelines Nudge but Don't Fully Budge
Depending on your point of view, the accumulated data is either dizzyingly complex and impossible to parse through or too limited to make any firm recommendations. Admittedly, we have to consider not just length of DAPT but also which anti-platelets to use as monotherapy and the clinical context of the patient. A high-ischemic-risk cardiac patient at low bleeding risk is very different from a high bleeding risk patient going for an elective PCI (percutaneous coronary intervention). We shouldn't blithely assume that what's true for clopidogrel is true for ticagrelor or that one antiplatelet is universally better in all populations. Also, most trials fail to consider one important consideration: cost.
Given all the new data from the last few years, you might think that clinical guidelines have evolved to incorporate or at least acknowledge the growing equipoise of how and when to inhibit platelets in cardiac patients. But the recent 2025 ACS guidelines still suggest a minimum 12 months of DAPT and give it a class 1A indication if the patient isn't at high bleeding risk. If they are, bleeding reduction strategies include transitioning to ticagrelor monotherapy after 1 month (Class 1A) and switching from ticagrelor or prasugrel to clopidogrel as part of the DAPT regimen (Class 2B). Monotherapy with any agent after 1 month also gets a 2b recommendation.
Although the guidelines are starting to budge on the issue, we seem to be perpetually locked into a 12-month DAPT mindset. The why is a fascinating question. It's partly because we are often more tolerant of bleeding than of cardiovascular events. We think we can manage bleeds whereas a stent thrombosis or a recurrent myocardial infarction feels like a failure.
Who follows up on the patient will also affect the duration of antiplatelet therapy. It's asking a lot of primary care providers to overrule the angiographer's recommendation of 12 months of DAPT post stent on the cath report.
A combination of uncertainty and inertia is keeping 12 months of DAPT alive. I'm as guilty as everyone else of falling into long established patterns. Habits are hard to break, but 24 years after CURE, we should acknowledge that 1 year of DAPT was never shown to be clinically superior to any other interval. Most of the contemporary data suggests that shorter durations are just as good if not better.
