Again and Again, Trials Back Short DAPT Post-PCI in ACS: Practice Slow to Shift

Despite getting even more new data this April supporting the practice of using ticagrelor monotherapy as soon as 1 month after PCI for ACS, many cardiologists seem wary about dropping aspirin so quickly in all but those at the highest bleeding risk.

The ULTIMATE-DAPT trial was presented by Gregg W. Stone, MD (Icahn School of Medicine at Mount Sinai, New York, NY), at the American College of Cardiology (ACC) 2024 Scientific Session and simultaneously published in the Lancet.

Among 3,400 patients who underwent PCI with DES and survived event free to 1 month on dual antiplatelet therapy (DAPT) with both ticagrelor and aspirin, the trial showed no difference in major adverse cardiovascular and cerebrovascular events—defined as cardiac death, MI, ischemic stroke, definite stent thrombosis, or clinically driven TVR—between those randomized to continue with ticagrelor plus either aspirin or placebo. Additionally, the rate of clinically-relevant bleeding (BARC 2, 3, or 5) at 12 months was significantly lower in the ticagrelor monotherapy group (2.1% vs 4.6%; HR 0.45; 95% CI 0.30-0.66).

While many at the ACC meeting seemed ready to make changes in their own practice and called for updates to the guidelines supporting shorter DAPT, as well, all the cardiologists who spoke with TCTMD in the wake of the conference admitted they themselves weren’t quite ready to follow suit.

Christopher Cannon, MD (Brigham and Women’s Hospital, Boston, MA), said he was reassured by the ULTIMATE-DAPT data, but that he is planning to “keep 1 year as my standard, followed by calculating the DAPT risk score and deciding on longer term.” If there is a higher risk for bleeding, then dropping aspirin sooner would now be an option. Citing the trial’s “moderate” size, he told TCTMD it could not be the “definitive word” on this topic.

Similarly, Sripal Bangalore, MD, MHA (NYU School of Medicine, New York), said ULTIMATE-DAPT builds on other studies supporting shorter courses of DAPT, including T-PASS, TALOS-AMI, and TOPIC. He’s a proponent of dropping aspirin early, but exactly when depends on patient characteristics, said Bangalore, adding, “I [use this strategy] in clinical practice routinely to de-escalate at 3 months (for those at high ischemic risk) and to de-escalate at 1-month for those at high bleeding risk.”

It's still very ‘murky waters’ for me, personally. Chandan Devireddy

Even with all the available data, Chandan Devireddy, MD (Emory University Hospital, Atlanta, GA), told TCTMD that making DAPT decisions is still a “pretty challenging path to navigate,” and that he would like to see the guidelines updated to reflect all the new evidence before changing his practice.

“With patients at high bleeding risk, I definitely have made moves to go to single antiplatelet agents. I feel the data and the guidance there is pretty robust,” Devireddy said. “Where I have trouble in this larger pool of both ACS and chronic ischemic heart disease is the number of variables that are still, I feel, involved in making this decision.”

Variables to Consider

Beyond the overall bleeding risk of the patient and the type of disease they have, Devireddy said components like PCI complexity, stent type, Impella use, IVUS guidance, and antiplatelet potency make it “tough to make the leap of faith for me personally to say full scale I'm changing to single agent antiplatelets 1 month after an ACS.” Having “dipped [his] toe in the water, very much in a case-by-case basis,” he said he remains worried about drug adherence, especially given that ticagrelor is taken twice daily, as well as expense. “It's still very ‘murky waters’ for me, personally.”

Srihari Naidu, MD (Westchester Medical Center, Valhalla, NY), too, brought up the issue of drug adherence with ticagrelor, something he said hasn’t been discussed enough.

We’re exploring this strategy on a case-by-case basis. Anuradha Tunuguntla

“In the context of a clinical trial, everybody's compliant,” he told TCTMD. “You're going to have people taking it twice a day for the duration of those 11 months. In the real world, I'm very much concerned that patients will drop off taking a dose here and there, and if the adherence rate is less, you have much less medication. And without the added aspirin, you don't have any fallback to make sure that you have antiplatelet therapy in your system. So we don't know in the real world whether this will hold up.”

Even if patients are completely adherent, “what you would do next is to try to find higher-risk patient populations to see if the benefit still holds,” Naidu continued. “Arguably the bleeding risk goes up in those populations and the ischemic risk goes up in those populations, and at some point it might be that it's not viable to be on monotherapy.”

The Tipping Point?

ULTIMATE-DAPT demonstrated that switching to monotherapy at 1 month may be an option in low-risk patients receiving “modern” PCI, Naidu said. As of yet, he hasn’t made any big changes to his practice, but he’s watching the evidence closely. “And I do have patients who I have over time dropped the aspirin,” he added. “But those tend to be patients who I feel that their risk overall was lower, either anatomically, clinically, or through comorbidities for stent thrombosis and they're usually at least 3 months out from their PCI.”

Anuradha Tunuguntla, MD (Nebraska Heart Institute, Lincoln), said she, too, has not yet incorporated 1-month of DAPT into her current practice, but called the ULTIMATE-DAPT data a “promising opportunity.”

“We acknowledge the advantages of reducing bleeding risk without compromising safety concerning ischemic events, especially in ACS PCI patients,” she said. “We’re exploring this strategy on a case-by-case basis, considering patient characteristics, bleeding, and ischemic risks.”

In the context of a clinical trial, everybody's compliant. Srihari Naidu

Generalizing the findings is difficult given the makeup of the ULTIMATE-DAPT trial population, which was mostly Chinese and included a mix of ACS patients, Tunuguntla highlighted. “With widespread use of high-sensitivity troponin assays, there has been a significant decline in true unstable angina cases, potentially leading to overlap with non-ACS patients,” she said.

While a single trial cannot alone change the guidelines, Tunuguntla said given the totality of the data she expects a “a notable evolution in guideline recommendations for reducing DAPT duration in post-ACS PCI patients.”

“We're at a tipping point,” Naidu added. “I think a couple, maybe even one or two more large-scale well-designed trials may completely be game changers for how we're doing this.”