Ticagrelor monotherapy following one month of dual antiplatelet therapy (DAPT) outperforms 12-month DAPT (aspirin and ticagrelor) post PCI for reducing clinically meaningful bleeding with no increased thrombotic risk, according to the results of the ULTIMATE-DAPT study, presented during a Late Breaking Clinical Trial session at ACC.24 and published simultaneously in The Lancet.

The placebo-controlled trial, conducted at 58 medical centers in China, Pakistan, Italy and the U.K., randomized 3,400 patients who had undergone DAPT for one month following PCI for an acute coronary syndrome (ACS) and had no adverse cardiovascular or bleeding events to either continuing DAPT or switching to ticagrelor and a placebo for 11 months. All patients had participated in the IVUS-ACS randomized trial, and all patients and staff interacting with the patients were blinded to the randomized assignment in the present study. Their median age was 62 years, most were men (74%) and Chinese (88%), and most (70%) had single-vessel disease. Transradial access was used in 97% of patients.

Results showed that the primary endpoint of clinically relevant bleeding (BARC 2, 3 or 5) at one year occurred in 4.6% of patients continuing DAPT and 2.1% of patients on ticagrelor monotherapy (hazard ratio [HR], 0.45; 95% CI, 0-30-0.66; p<0.0001). The composite primary endpoint of major adverse cardiovascular events and cerebrovascular (MACCE) events showed no significant difference between groups, with 3.7% of patients who continued DAPT and 3.6% of those taking ticagrelor monotherapy experiencing such events (HR, 0.98; 95% CI, 0.69-1.39; p for noninferiority <0.0001; p for superiority =0.89). No significant interactions were seen across the 12 prespecified subgroups for clinically relevant bleeding or MACCE.

Additionally, net adverse clinical events (MACCE or BARC types 1-5 bleeding) were lower in the ticagrelor monotherapy group vs. DAPT group (5.7% vs. 8.2%; p=0.007).

"In treating a broad range of patients with [ACS] in the era of contemporary drug-eluting stents, among those who were stable after one month of DAPT, continuing treatment with ticagrelor alone reduced bleeding with no increase in adverse ischemic thrombotic events," said Gregg W. Stone, MD, FACC, co-chair of the trial. "These data suggest that a 12-month duration of DAPT is not only not necessary in most patients with ACS but is harmful."

"The next question is how will physicians incorporate these results into their daily practice, and what will guideline committees ultimately do with these data," Stone said. "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 one month of DAPT followed by a potent P2Y12 inhibitor such as ticagrelor in most patients with ACS after successful PCI." Stone noted that separate studies are needed to investigate the safety and efficacy of a similar approach using other P2Y12 inhibitors, such as prasugrel and clopidogrel.

In an accompanying editorial comment, Gloria M. Steiner-Gager, MD, and Jolanta M. Siller-Matula, MD, PhD, wrote that "careful consideration regarding the broader geographical generalizability of these findings in warranted," noting that despite it being a multicenter study, 98.7% of patients were from China and Pakistan. "Given the acknowledged higher bleeding risk observed in patients from East Asia, the applicability of a 1-month [DAPT to other regions necessitates evaluation," they wrote, adding the question remains open regarding appropriate therapy 12 months after [PCI].