Short DAPT Noninferior to 1 Year After Ultrathin DES PCI: HOST-IDEA

Among patients receiving PCI with a third-generation DES with ultrathin struts and advanced polymer technology, 3 months of dual antiplatelet therapy (DAPT) is noninferior to 12 months in terms of net adverse clinical events (NACE) at 12 months, according to new randomized data from the HOST-IDEA trial.

While current guidelines recommend patients with stable ischemic heart disease receive 6 months of DAPT and those with ACS receive 12 months, the promise of the newest-generation DES like the Orsiro (Biotronik) and Coroflex ISAR (B. Braun) used in this study is that they would minimize the risk of stent-related complications, thereby shortening DAPT requirements, explained Hyo-Soo Kim, MD (Seoul National University Hospital, Republic of Korea), who presented the results at the American College of Cardiology/World Congress of Cardiology (ACC/WCC) 2023 meeting.

Commenting on the findings for TCTMD, Roxana Mehran, MD (Icahn School of Medicine at Mount Sinai, New York, NY), who was not involved in the study, said she actually would have expected investigators to be able to show superiority of shorter DAPT with these devices, at least with regard to bleeding. But in fact, she said, “bleeding rates were quite low and their event rates, in general, were extremely low,” meaning the comparison was underpowered for superiority and “almost not even there for noninferiority.”

Still, the study “really gives you some level of confidence that you can shorten dual antiplatelet therapies in patients with thin-strut [stents], including and especially [with] the Orsiro stent,” Mehran said. That device has US Food and Drug Administration approval based on the BIOFLOW V study, demonstrating superiority over the thin-strut, durable-polymer Xience stent (Abbott), “so I feel very confident already doing that.”

DAPT After PCI With Ultrathin-Strut DES

For HOST-IDEA, which was simultaneously published in Circulation, Jung-Kyu Han, MD (Seoul National University Hospital, Republic of Korea), Kim, and colleagues included 2,013 patients (mean age 65.7 years; 73.9% male) undergoing PCI with either the Orsiro or Coroflex ISAR DES at one of 37 Korean centers between January 2016 and May 2021. Slightly under half presented with stable ischemic heart disease, about one-third had unstable angina, and the rest had NSTEMI—STEMI patients were excluded. Total stent length was 29.2 mm, and patients on average received 1.6 stents.

Patients were randomized to receive 3 months of DAPT followed by single antiplatelet therapy of their physician’s choosing (n = 1,002) or 12 months of DAPT (n = 1,011). Aspirin plus clopidogrel was by far the most common DAPT combination, with about 89% of all patients receiving this pairing, but ticagrelor and prasugrel were used instead of clopidogrel in 8.5% and 2.4% of patients, respectively.

The primary outcome of NACE—comprised of cardiac death, target-vessel MI, clinically driven TLR, stent thrombosis, and BARC 3 or 5 bleeding—was similar at 12 months between the short- and long-term DAPT groups, meeting the threshold for noninferiority (3.7% vs 4.1%; HR 0.93; 95% CI 0.60-1.45; P < 0.001). Similarly, there were no differences between any of the individual secondary endpoints, including the patient-oriented composite outcome of all-cause death, any MI, any revascularization, or stroke (6.0% vs 6.9%; HR 0.88; 95% CI 0.62-1.24), as well as major bleeding (BARC 3 or 5; 1.5% vs 1.9%; HR 0.82; 95% CI 0.41-1.61) or minor bleeding (BARC 2; 3.7% vs 5.0%; HR 0.75; 95% CI 0.49-1.15).

The results were consistent through all prespecified subgroup analyses, per protocol analyses, and among those who only took clopidogrel or only more-potent P2Y12 inhibitors.

Kim acknowledged that the event rates seen in the study were substantially lower than the researchers had initially predicted but on par with what has been seen in other contemporary studies. “This made the noninferiority margin of 3.2% too wide,” he said. Additionally, because the study was an open-label trial, nonadherence biases may have been introduced.

Were she to redesign the trial, Mehran said, it “would need at least twice as many patients in order to show [superiority] certainly, and I would want to know what kind of a single antiplatelet therapy these patients were given. Given that the HOST investigators have already shown a superiority of clopidogrel monotherapy versus aspirin, I would have thought that their single antiplatelet therapy would be clopidogrel. And then it would really show a difference.”

She didn’t fault the researchers for being as “pragmatic as possible” in letting clinicians choose what drugs to use for each patient. “But I think when you look at this overall, what catches my eye is the fact that they are just not showing any difference at all,” Mehran continued. “We know that less is more. When you do 3 months of DAPT, you are going to have to gain something in terms of your bleeding endpoint and when they don't show any difference at all, it makes you wonder: how could this be possible?”

Kim pointed out that the study shows good performance of clopidogrel in an Asian population known for having a higher prevalence of the loss of function allele, which might affect performance of the drug. “Although more than half of the patients in our study presented with ACS,” Kim said, “a majority used clopidogrel showing excellent results.”

HOST-EXAM Extended Data

More DAPT insights come from another study presentation by the same research group earlier in the month at CRT 2023, where Kyung Woo Park, MD (Seoul National University Hospital), presented extended results from HOST-EXAM. Here, as previously reported by TCTMD, investigators demonstrated superiority of clopidogrel over aspirin monotherapy with regard to a patient-oriented composite outcome out to 2 years in stable CAD patients who were event free after 12 months of DAPT.

The new data conclude that this result is consistent regardless of whether patients presented with ACS (HR 0.78; 95% CI 0.66-0.92) or non-ACS (HR 0.82; 95% CI 0.63-1.06; P = 0.751 for interaction).

“The risk reduction by clopidogrel monotherapy tended to be more pronounced for the thrombotic risk in patients with ACS and for the bleeding risk in patients with non-ACS,” Park said at the meeting.

Commenting on the study following its presentation, co-moderator Gregg Stone, MD (Icahn School of Medicine at Mount Sinai, New York, NY), said, “It's remarkable to me that after 30 randomized trials of antiplatelet agent escalation, de-escalation, more-potent agents, less-potent agents, stopping agents, restarting agents, we still are debating the optimal use of antiplatelet agents in 2023.”

Being able to differentiate between ACS and non-ACS patients, as was done here, is important because the former are often younger and have greater thrombotic risk, he continued. “So you think you might need more potent antiplatelet agents.”

To have this extended follow-up data confirms a “very, very good beneficial effect of clopidogrel, very consistent with their original findings,” Mehran said. “And it was even more pronounced in the ACS patient population, especially in the bleeding risk, which makes a lot of sense because ACS patients are at higher risk of bleeding and they had even a better benefit.”

Even with all the studies of DAPT, the field is “extremely complex now with so many permutations and so many choices for patients at different times after PCI,” Mehran said. “It is not just the type of antiplatelet regimen. It is the timing of it: it's for how long, in whom, when do you stop, and how long after a PCI?”

This all leads to the perfect opportunity to use machine learning to optimize precision medicine for these patients, she concluded—a project she says she herself is working on now.