Ticagrelor Monotherapy Following 3-Month DAPT Cuts Post-PCI Bleeding After STEMI

(UPDATED) Even in STEMI patients undergoing PCI, switching to ticagrelor (Brilinta; AstraZeneca) monotherapy after 3 months of ticagrelor-based dual antiplatelet therapy (DAPT) appears to be a safe strategy, a prespecified subgroup analysis of the TICO trial shows.

Compared with patients who stayed on ticagrelor plus aspirin, those who dropped aspirin after the first 3 months had a lower rate of TIMI major bleeding at the 1-year mark (0.9% vs 2.9%; HR 0.32; 95% CI 0.12-0.87), according to Byeong-Keuk Kim, MD, PhD (Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea).

That advantage did not come at the expense of more MACCE (2.7% vs 2.5%; HR 1.09; 95% CI 0.53-2.27), he reported during TCT Connect 2020.

Other trials—namely, GLOBAL LEADERS and TWILIGHT—have explored the idea of using potent P2Y12 inhibitor monotherapy after 1 to 3 months of DAPT in patients with either stable coronary disease or ACS (proportions of ACS in the two trials were 47% and 65%, respectively). The idea is that the strategy will better balance risks of bleeding and ischemia. TICO, which included patients with ACS exclusively, included the largest proportion of STEMI—36.1% of participants versus 13.1% in GLOBAL LEADERS and none in TWILIGHT.

Results in this STEMI subgroup analysis mirrored those in the overall TICO trial, with less bleeding and no increase in ischemic events with ticagrelor monotherapy beyond 3 months.

“However, care should be taken in applying these results to the overall STEMI population, especially those at high risk for ischemia,” Kim said during a press briefing.

Commenting for TCTMD, David Fischman, MD (Thomas Jefferson University Hospitals, Philadelphia, PA), said the findings, along with those from the other trials, give “food for thought” about DAPT duration after PCI in patients with ACS but should not change practice just yet. He said he’s still routinely sticking with 12 months of DAPT and suspects most other physicians are, too, noting: “My general sense of things is that people, in the ACS population, have not backed off on DAPT yet.”

An informal poll Fischman started on Twitter, which attracted 63 votes, appeared to bear that out—60.3% of respondents said they have not shortened the duration of DAPT in their ACS patients based on the results of TWILIGHT and TICO.

TICO-STEMI

The TICO trial, performed at 38 centers in South Korea, randomized patients with ACS—split roughly evenly between unstable angina, NSTEMI, and STEMI—who were treated with the ultrathin-strut, bioresorbable-polymer, sirolimus-eluting Orsiro stent (Biotronik) to 12 months of DAPT with ticagrelor plus aspirin or to 3 months of DAPT followed by 9 months of ticagrelor monotherapy. The prespecified subgroup analysis presented by Kim focused on the 1,103 patients with STEMI.

My general sense of things is that people, in the ACS population, have not backed off on DAPT yet. David Fischman

The primary outcome was net adverse clinical events (NACE), a composite of TIMI major bleeding and MACCE (all-cause death, MI, stent thrombosis, stroke, or TVR). NACE was numerically, but not significantly, lower in the group that received shortened DAPT (3.7% vs 5.0%; HR 0.73; 95% CI 0.41-1.29) in the intention-to-treat analysis. The difference reached significance in an as-treated analysis (2.3% vs 5.2%; HR 0.44; 95% CI 0.23-0.86).

TIMI major bleeding was reduced in the monotherapy group in both the intention-to-treat and as-treated analyses, whereas MACCE was not statistically different between groups in either.

Post hoc analyses showed that ticagrelor monotherapy reduced TIMI major bleeding compared with 12-month DAPT regardless of patients’ bleeding risk as defined by the PRECISE-DAPT score (P = 0.69 for interaction). The complexity of PCI also did not significantly influence the results (P = 0.17 for interaction), although the highest rate of MACCE was seen in patients who underwent complex PCI and received shortened DAPT.

Marco Valgimigli, MD, PhD (Bern University Hospital, Switzerland), acknowledging the nonsignificant interactions, indicated it was worth taking a closer look at those post hoc results. He pointed out that in patients with high PRECISE-DAPT scores, the number needed to treat to prevent one major bleed with ticagrelor monotherapy was 22, whereas the NNT was 77 in those with lower bleeding risks. “I think from a clinical standpoint, this treatment strategy seems particularly appealing in [high-bleeding-risk] patients,” he said

On the other hand, he added, the data hinting at increased MACCE in patients who underwent complex PCI and received ticagrelor monotherapy after 3 months “are really not reassuring and probably worth another investigation.”

‘Pretty Provocative’

At a press briefing, moderator Ajay Kirtane, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), called the findings “pretty provocative . . . yet reassuring.”

Other panelists pointed out that decisions about DAPT duration after PCI are not made at the time of the procedure—when randomization was performed in TICO—but after the initial months, when risks of bleeding and ischemic events are highest. Only after seeing how patients respond early on can decisions be made about whether to continue DAPT or move forward with a single agent, they said. “For me, you have to wait before you decide how long you should give the dual antiplatelet therapy,” Adnan Kastrati, MD (Deutsches Herzzentrum München, Munich, Germany), said, noting that that’s why randomization was performed at 3 months after PCI in the TWILIGHT trial.

Gregg Stone, MD (Icahn School of Medicine at Mount Sinai, New York, NY), agreed that “you have to make the decision at the point in time at which you’re considering actually changing the antiplatelet regimen, whether that’d be 1 month or 3 months.”

Still, he indicated that the TICO findings, along with those from other trials, could have an impact on practice. “In concert with TWILIGHT, this study—which is excellent—is very consistent in showing the safety of dropping aspirin at 3 months in patients who are treated with ticagrelor after a STEMI or acute coronary syndrome or high-risk PCI, and I think I would consider that in practice,” Stone said. “I think these trials collectively have been practice-changing, particularly in high-bleeding-risk patients or those with some risk factors.”

Fischman said he would like to see a dedicated trial in STEMI before considering routine use of shortened DAPT in that population,and Roxana Mehran, MD (Icahn School of Medicine at Mount Sinai), said the design of a TWILIGHT-STEMI trial is in the works. 

Right now, some patients need to have their therapy cut short either due to a bleeding episode or because of emergent surgery, Fischman pointed out, adding that in his practice patients typically continue on aspirin alone after that. “I’m not promoting that, but that’s what we do,” he said, explaining that surgeons and dentists don’t like to perform procedures on patients treated with P2Y12 inhibitors. “I’m not saying this is the right thing to do, but we have to make a choice, we have to weigh the risks and benefits in terms of cardiac events, stent thrombosis versus the bleeding episodes.”

He stressed, however, that if shortened DAPT followed by a single antiplatelet agent eventually becomes the norm in ACS patients based on further evidence, “you wouldn’t use aspirin, you would use a more potent agent.”