麻豆传媒

ATLANTA -- In select patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes who were event-free for 1 month on dual antiplatelet therapy (DAPT), treatment with ticagrelor (Brilinta) alone between 1 month and 12 months resulted in a lower rate of clinically relevant bleeding and a similar rate of major adverse coronary or cerebrovascular events (MACCE) compared with ticagrelor plus aspirin, the ULTIMATE-DAPT trial showed.

Between 1 to 12 months after PCI, clinically relevant bleeding occurred in 2.1% of patients in the ticagrelor plus placebo group versus 4.6% of those in the ticagrelor plus aspirin group (HR 0.45, 95% CI 0.30-0.66, P<0.0001), reported Gregg Stone, MD, of the Icahn School of Medicine at Mount Sinai in New York City, during the American College of Cardiology annual meeting and in .

MACCE occurred in 3.6% of patients in the ticagrelor plus placebo group compared with 3.7% in the ticagrelor plus aspirin group (HR 0.98, 95% CI 0.69-1.39, P for non-inferiority<0.0001, P for superiority=0.89).

Stone suggested that the findings of the study are robust enough to change practice guidelines: not only was ticagrelor alone non-inferior to ticagrelor plus aspirin, but the single use of ticagrelor after a month reduced bleeding episodes markedly, he said.

International guidelines currently recommend DAPT with aspirin plus a potent P2Y12 inhibitor for 12 months in most patients presenting with acute coronary syndromes treated with PCI to prevent myocardial infarction (MI) and stent thrombosis, Stone noted.

"It was previously believed that discontinuing DAPT within 1 year after PCI in patients with acute coronary syndromes would increase the risk of heart attack and other ischemic complications, but the present study shows that is not the case, with contemporary drug-eluting stents now used in all PCI procedures," Stone said. "This study extends the results of prior work that showed similar results but without the quality of using a placebo, which eliminates bias from the study."

"These data suggest that a 12-month duration of DAPT is not only not necessary in most patients with acute coronary syndromes but is harmful," he added. "I believe these results are very convincing and align with prior studies done without a placebo; hopefully they will impact guidelines and lead to the routine use of only 1 month of DAPT followed by a potent P2Y12 inhibitor such as ticagrelor in most patients with acute coronary syndromes after successful PCI."

Changing the guidelines, however, may require more than one study, suggested Rajiv Jauhar, MD, of North Shore University Hospital/Northwell Health in Manhasset, New York.

"While we are in an era of de-escalation of medication across medical fields, the mantra of dual antiplatelet therapy is so well-embedded into the care of patients who have undergone stent implantation that even nurses in our hospitals tell patients they must stay on their aspirin and ticagrelor or clopidogrel [Plavix]," Jauhar told 麻豆传媒.

"There are limitations to this study -- especially because it was done in China and in a particular region of China, even though it is unlikely that the mechanism of action of ticagrelor is ethnic-specific," he said. "I suspect that these data could be extrapolated to the general population. It will take some real-world experience before it can overcome inertia in medicine to change practice."

"I think we are going to need a couple of more studies that support these findings before guidelines -- and clinical practice -- will change," he added. "I don't think we will see physicians changing their extended use of dual antiplatelet therapy very soon."

Questions regarding the study population were also raised by Gloria Steiner-Gager, MD, and Jolanta Siller-Matula, MD, PhD, both of the Medical University of Vienna, in an .

They noted that only 1.3% of the participants were Europeans, while the rest were from China and Pakistan. "Given the acknowledged higher bleeding risk observed in patients from East Asia, the applicability of a 1-month dual antiplatelet therapy regimen followed by ticagrelor monotherapy to other regions necessitates evaluation," they wrote.

They also said that the choice of which antiplatelet therapy would be appropriate after transitioning from DAPT is also unresolved. "These concerns await resolution in future trials, which should aim to ascertain the tailored dual antiplatelet therapy combination duration following acute coronary syndrome," they suggested.

In the , mainly conducted in China, the researchers included patients who had a heart attack or who were at risk for a heart attack and who underwent PCI to implant drug-eluting stents.

After taking ticagrelor and aspirin for 30 days after successful PCI, 1,700 patients were randomly assigned to receive ticagrelor plus aspirin and were followed for 1 year; another group of 1,699 patients (one patient was lost to follow-up) were assigned to receive ticagrelor and placebo. The patients were selected from 58 facilities in China, Italy, Pakistan, and the U.K. and were recruited into the study from September 2019 to October 2022.

Median age was 62-63, 74% were men, and 87-89% were Chinese. Roughly 62% had hypertension, 32% had diabetes, 68-69% had dyslipidemia, and 28-29% were current smokers.

Of the patients, 39-42% were undergoing PCI because of unstable angina, and 58-61% had acute MI.

The primary non-inferiority endpoint of MACCE was defined as a composite of cardiac death, MI, ischemic stroke, definite stent thrombosis, or clinically driven target vessel revascularization, with an expected event rate of 6.2% in the ticagrelor plus aspirin group and an absolute non-inferiority margin of 2.5 percentage points between 1 month and 12 months after PCI.