Long-term DAPT may not be needed for patients with ACS after angioplasty, stenting
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Key takeaways:
- In patients with ACS who had angioplasty and stenting, ticagrelor monotherapy after 1 month reduced bleeding vs. ticagrelor plus aspirin for 12 months.
- The groups did not differ in ischemic events.
ATLANTA — In patients with ACS who underwent PCI, ticagrelor monotherapy after 1 month lowered bleeding risk by 55% compared with dual antiplatelet therapy for 12 months, according to the results of the ULTIMATE-DAPT trial.
There were no differences between the ticagrelor monotherapy strategy and the 12-month DAPT strategy in any ischemic outcomes, according to the findings, which were presented at the American College of Cardiology Scientific Session and simultaneously published in The Lancet.
‘It’s time to change the guidelines’
“To be honest, it’s time to change the guidelines,” Gregg W. Stone, MD, professor of cardiology and population health sciences at Icahn School of Medicine at Mount Sinai and director of academic affairs for the Mount Sinai Health System, said at a press conference. “It’s time to change clinical practice patterns.”
ULTIMATE-DAPT was part of a 2x2 factorial study along with IVUS-ACS. After patients underwent PCI with a contemporary drug-eluting stent and completed the IVUS-ACS study, if they had no major ischemic or bleeding events after 1 month of DAPT consisting of ticagrelor (Brilinta, AstraZeneca) and aspirin, they were randomly assigned to continue DAPT or to receive ticagrelor monotherapy (ticagrelor plus placebo) until 12 months after their procedure, Stone said during the presentation.
The ULTIMATE-DAPT cohort consisted of 3,400 patients, all but one of whom completed 12-month follow-up. The primary superiority endpoint was clinically relevant bleeding, defined as Bleeding Academic Research Consortium (BARC) types 2, 3 or 5, at 12 months. The primary noninferiority endpoint, which was to be tested only if the primary superiority endpoint favored ticagrelor monotherapy, was major adverse cardiac and cerebrovascular events, defined as cardiac death, MI, ischemic stroke, definite stent thrombosis or clinically driven target vessel revascularization, at 12 months.
During the study period, clinically relevant bleeding occurred in 2.1% of the ticagrelor monotherapy group and 4.6% of the 12-month DAPT group, for a relative risk reduction of 55% (HR = 0.45; 95% CI, 0.3-0.66; P < .0001), Stone said during the presentation.
The relative risk reduction with ticagrelor monotherapy for major bleeding, defined as BARC type 3 or 5, was 61% (HR = 0.39; 95% CI, 0.19-0.79; P = .009), he said, noting that ticagrelor monotherapy was also superior for TIMI major or minor bleeding, TIMI major bleeding, Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) moderate, severe or life-threatening bleeding, International Society on Thrombosis and Haemostasis (ISTH) major bleeding, and individually BARC type 2 bleeding and BARC type 3 bleeding.
The primary noninferiority endpoint occurred almost identically in both groups (monotherapy, 3.6%; DAPT, 3.7%; HR = 0.98; 95% CI, 0.69-1.39; P for noninferiority < .0001; P for superiority = .89), Stone said, noting there were no differences between the groups in any ischemic outcomes.
Net adverse clinical events, defined as MACCE or BARC types 1 to 5 bleeding, were reduced by 32% in the monotherapy group compared with the long-term DAPT group (HR = 0.68; 95% CI, 0.53-0.88; P = .007), he said.
The primary bleeding and ischemic outcomes were consistent in all subgroups except for age in the primary ischemic outcome, in which monotherapy was more favorable in patients younger than 65 years and long-term DAPT was more favorable in patients aged 65 years or older (P for interaction = .02), according to the researchers.
‘We’ve got the data now’
“Most patients with acute coronary syndromes who have successful PCI with contemporary drug-eluting stents, which are much safer than prior iterations of devices, should now be managed with a P2Y12 inhibitor alone after a 1-month course of DAPT,” Stone said at the press conference. “The best data so far are with ticagrelor. Whether prasugrel would provide similar results is unknown, but is a reasonable expectation. I wouldn’t go so far in suggesting the same for clopidogrel, which is much less potent. We’ve got the data now. It’s time to change practice and the guidelines, and by dropping aspirin at 1 month after PCI when it is no longer needed, we can prevent more than half of major bleeds while equally preserving low ischemic event rates.”
Reference:
Perspective
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I think this will move the needle. We have been so fascinated with clotting after coronary stenting after heart attacks. In the last 5 to 10 years, we have realized the importance of bleeding much more. This trial is the one singular trial that I have seen that moves us as far forward to single antiplatelet therapy as any other study has. It tells us with pretty good confidence, at least in this population studied, that after 30 days of dual antiplatelet therapy, we can safely go down to single antiplatelet therapy in the form of ticagrelor. Whether or not that holds true for prasugrel, we will need to study, but certainly for this particular trial, ticagrelor looked excellent. I was pleased to see that not only did it reduce bleeding, we did not seem to have any increased risk for major adverse cardiac events.
We have to be a little careful about extrapolating it to all patients. There are some patients who are at high risk for clotting from stents. For example, patients with degenerated vein grafts, patients who have large thrombus burden noticed by the interventional cardiologist and other high-risk patients who have heart failure, have very low ejection fraction and continue to smoke. We may need to continue DAPT in some of those patients. But for the garden-variety patients who fit the inclusion criteria for this study, this is life-changing. We are actually doing harm by overprescribing medications in these patients. The net clinical benefit is a summation of not only clotting, but bleeding. We are now seeing that we don’t have to cheat the patient on clotting to get rid of a lot of the bleeding. That is huge.
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Stone GW, et al. Joint American College of Cardiology/New England Journal of Medicine Late-breaking clinical trials III. Presented at: American College of Cardiology Scientific Session; April 6-8, 2024; Atlanta.
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