ULTIMATE-DAPT Evaluates Ticagrelor Monotherapy After 1 Month of DAPT Post PCI in ACS Patients

April 7, 2024—The ULTIMATE-DAPT study showed that patients who have had (or are at risk for) a heart attack and stopped taking aspirin alongside ticagrelor at 1 month after percutaneous coronary intervention (PCI) experienced a significantly reduced risk of clinically meaningful bleeding with no increased risk of clotting-related adverse events at 12 months, compared with patients who continued taking aspirin and ticagrelor for a full year.

According to the American College of Cardiology (ACC), the ULTIMATE-DAPT study is the first placebo-controlled trial designed to examine monotherapy with ticagrelor, a P2Y12 inhibitor, after 1 month of dual antiplatelet therapy (DAPT) post PCI. The study focused on patients who underwent PCI for acute coronary syndrome (ACS) with stents containing drugs to prevent further plaque buildup.

Findings were presented by trial cochair Gregg Stone, MD, at the ACC.24 Annual Scientific Session held April 6-8 in Atlanta, Georgia, and simultaneously published online by Zhen Ge, MD, et al in The Lancet.

Dr. Stone is Professor of Cardiology and Population Health Sciences at Icahn School of Medicine at Mount Sinai in New York, New York.

“In treating a broad range of patients with ACS in the era of contemporary drug-eluting stents, among those who were stable after 1 month of DAPT, continuing treatment with ticagrelor alone reduced bleeding with no increase in adverse ischemic thrombotic events,” commented Dr. Stone in the ACC press release. “These data suggest that a 12-month duration of DAPT is not only not necessary in most patients with ACS but is harmful.”

The ACC press release noted that current guidelines recommend that most patients should take two antiplatelet medications—aspirin and a P2Y12 inhibitor—for a full year to reduce the risk of clotting-related cardiovascular problems such as heart attacks and strokes. However, the bleeding risk associated with antiplatelet medications has fueled efforts to further optimize the duration of post-PCI antiplatelet therapy and the medications used to balance the benefits and risks.

As summarized by ACC, the ULTIMATE-DAPT investigators enrolled 3,400 patients who experienced no adverse cardiovascular or bleeding events in the first month after PCI for ACS at 58 medical centers in four countries in Asia and Europe.

During the first 30 days after PCI, all patients took aspirin and ticagrelor. Patients were then randomly assigned to continue with this same regimen for 11 additional months or switch to ticagrelor and a placebo.

The ACC press release stated that the ULTIMATE-DAPT trial met its two primary endpoints of efficacy in terms of bleeding risk and safety in terms of clotting-related events. The first endpoint, clinically relevant bleeding, occurred in 4.6% of patients assigned to continuing DAPT and 2.1% of patients assigned to take ticagrelor and a placebo, a significant reduction in favor of ticagrelor alone. The second endpoint, a composite of major adverse cardiovascular events and cerebrovascular events, showed no significant difference between groups, with 3.7% of patients who continued DAPT and 3.6% of those taking ticagrelor and a placebo experiencing such events.

The investigators concluded that treating ACS patients with ticagrelor alone 1 month after PCI was equally safe and effective in patients who presented with a heart attack (the highest risk group) or were at risk of a heart attack. Together, these findings suggest that patients who stopped taking aspirin after the first month had a substantially reduced risk of bleeding without any increased risk of thrombotic events.

“The next question is how will physicians incorporate these results into their daily practice, and what will guideline committees ultimately do with these data,” stated Dr. Stone. “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 ACS after successful PCI.”

The investigators advised that because the trial only involved ticagrelor, separate studies would be necessary to investigate the safety and efficacy of a similar approach using other P2Y12 inhibitors, such as prasugrel and clopidogrel.