Solo ticagrelor after 1-month DAPT: Is it time to change practice?

Dropping aspirin for ticagrelor monotherapy 1 month after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) is as good as dual antiplatelet therapy (DAPT) in the ULTIMATE-DAPT* trial presented at ACC.24.

However, going for solo ticagrelor after 1 month of dual therapy with ticagrelor and aspirin had the advantage of less bleeding while offering patients similar protection from major adverse cardiovascular or cerebrovascular events (MACCE). [Ge Z, et al, ACC 2024, Late Breaking Session]

“I believe this trial, in concert with all the previous trials, dictates a time for practice change, even before new guidelines come out, as there is evidence from dozens of randomized trials now, including this study, which arguably is the most rigorous,” said study investigator Dr Gregg Stone from Icahn School of Medicine at Mount Sinai, New York City, New York, US at ACC.24.

Dr Usman Baber from the University of Oklahoma Health Sciences Center, Oklahoma City, Oklahama, US, who was not involved in the trial, could not agree more. “Guidelines in Europe and the US have already adopted P2Y12 inhibitor monotherapy as a strategy. I believe future iterations of the guidelines may reinforce that and can certainly consider an earlier time to discontinue aspirin.”

 More evidence for solo ticagrelor

The results of ULTIMATE-DAPT provide the strongest evidence around the safety and efficacy of withdrawing aspirin 1 month after index presentation and continuing with solo ticagrelor.

The data also support findings from the TWILIGHT and TICO trials, which dropped aspirin at 3 months for ticagrelor monotherapy in stented patients with ACS. [N Engl J Med 2019;381:2032-2042; JAMA 2020;323:2407-2416]

A post hoc analysis of the GLOBAL LEADERS trial also demonstrated the safety of ticagrelor monotherapy following a month of DAPT. [EuroIntervention 2020;16:634-644] In the more recent T-PASS trial, stopping aspirin within 1 month for ticagrelor monotherapy was superior to 12-month DAPT. [Circulation 2024;149:562-573]

Study discussant Dr David Moliterno from the University of Kentucky in Lexington, Kentucky, US, noted that the insights come after almost two decades of protracted DAPT in the ACS post-PCI setting. “We’re finally getting to the point where we can shorten the duration of our DAPT.”

ULTIMATE-DAPT population

Researchers enrolled 3,400 patients (mean age 62 years, 74 percent male) from the IVUS-ACS study who underwent PCI with a drug-eluting stent and survived event-free to 1 month of DAPT with ticagrelor and aspirin. They were then randomly assigned to continue with ticagrelor plus either aspirin or a placebo. [Lancet 2024;doi:10.1016/S0140-6736(24)00473-2]

Clinically relevant bleeding (BARC** 2, 3, or 5) at 1 year, the trial’s primary outcome of interest, was significantly less often in the solo ticagrelor cohort than the DAPT cohort (2.1 percent vs 4.6 percent, hazard ratio [HR], 0.45, 95 percent confidence interval [CI], 0.30–0.66).

Similar findings were observed for major bleeding, whether defined as BARC 3 or 5, BARC 2, BARC 5, TIMI major or minor; GUSTO moderate, severe, or life-threatening; or ISTH major. No differences were observed in the subgroup analyses.

MACCE, the composite outcome of cardiac death, myocardial infarction, ischaemic stroke, definite stent thrombosis, or clinically driven target vessel revascularization, were similar between the solo ticagrelor and DAPT cohorts (3.6 percent vs 3.7 percent, HR, 0.98, 95 percent CI, 0.69–1.39; p for noninferiority <0.0001; p for superiority=0.89).

Interestingly, net adverse clinical events (NACE), defined as MACCE or BARC types 1–5 bleeding, was lower in the solo ticagrelor cohort than the DAPT cohort (5.7 percent vs 8.2 percent, HR, 0.68, 95 percent CI, 0.53–0.88).

Study not without limitations

However, Stone cautioned that 88 percent of the patients were from China, potentially limiting the generalizability of the findings. Another caveat is that patients in the study had no complex disease at baseline.

“Seventy percent of the patients had single-vessel disease, <10 percent had severe calcium or thrombus. This was reflected in the low rates of ischaemic events overall,” Baber said. “Nevertheless, I would be comfortable [withdrawing aspirin] in patients whom I think have lower thrombotic risk.”

The way forward

Stone said he would also be comfortable dropping aspirin 1-month post-PCI in most ACS patients who have tolerated the drug without events until that point. “In fact, I have already been recommending this approach to my ACS patients.”

However, he said he would caution against ticagrelor monotherapy in patients who had events before 1 month and those who had highly complex PCI procedures, including those with ≥4 stents, complex bifurcation or small-vessel stents, and residual disease. “But these are a minority of patients we must decide individually.”

Stone added that it would be interesting to see a head-to-head trial between ticagrelor and other P2Y12 inhibitors, such as prasugrel, incorporating an aspirin-free strategy in the setting of more complex coronary artery disease.