A second trial has shown benefit of stopping aspirin 3 months after stenting and continuing solely with ticagrelor monotherapy.
The Ticagrelor With or Without Aspirin in Acute Coronary Syndrome After PCI (reported last year. But whereas TWILIGHT enrolled a more general PCI population, TICO included only patients with acute coronary syndrome (ACS).) study shows very similar results as the TWILIGHT trial
The South Korean TICO trial was presented today at the “virtual” American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology.
Presenting the study, senior investigator Yangsoo Jang, MD, PhD, professor of cardiology at Yonsei University College of Medicine in Seoul, South Korea, concluded: “Ticagrelor monotherapy after 3-month dual antiplatelet therapy showed a significantly lower risk of net adverse clinical events than currently recommended ticagrelor-based 12-month dual antiplatelet therapy. The reduced risk was mainly due to decreased major bleeding.”
These findings indicate that ticagrelor monotherapy “could be an optimal strategy that balances both ischemic and bleeding risks for patients with ACS,” he added.
Discussant of the TICO study, Deepak Bhatt, MD, Brigham and Women’s Hospital, Boston, said: “This is an independent confirmation of TWILIGHT. To have two independent trials reaching the same conclusion — that the regimen of ticagrelor monotherapy after 3 months dual antiplatelet therapy essentially cuts major bleeding in half — is very comforting.”
Michelle O’Donoghue, MD, also from Brigham and Women’s and chair of the ACC session at which the study was presented, added, “A particular strength of this trial was that you had an all-ACS population.”
Enough to Change Guidelines?
Discussing the trial at an ACC press conference, Claire Duvernoy, MD, University of Michigan, Ann Arbor, suggested that the results from TICO and TWILIGHT together are “enough evidence to change the guidelines. I think we are there,” she added.
“TICO adds to our expanding body of evidence for newer, more potent, P2Y12 inhibitors as monotherapy. This trial stands out as the only exclusive ACS study looking at this and the only trial enrolling a significant population of STEMI patients,” Duvernoy said.
She pointed out one caveat — the need to discontinue ticagrelor because of dyspnea, which she said occurs in around 10%-15% of patients in her practice.
“Also, both TICO and TWILIGHT used the latest second-generation drug-eluting stents, which may have better safety and allows us to get away with less antiplatelet therapy,” Duvernoy noted.
The TICO trial, conducted at 38 centers in South Korea, enrolled 3056 patients with ACS (average age 61 years) undergoing PCI and stenting with the second-generation ultrathin biodegradable polymer-coated sirolimus-eluting stents (Biotronik).
All patients received ticagrelor plus aspirin for 3 months, then were randomly assigned to continue treatment with ticagrelor and aspirin or ticagrelor alone.
The primary study endpoint was a net clinical benefit composite of death, MI, stroke, stent thrombosis, revascularization, or TIMI major bleeding at 12 months. This occurred in 3.9% of those randomly assigned to ticagrelor alone vs 5.9% of those who continued on dual antiplatelet therapy, giving a hazard ratio of 0.66 (P = .01).
The curves separated early with a marked difference in event rate being seen at 3 months after randomization. At this point, rates of the composite endpoint were 1.4% in the ticagrelor monotherapy group vs 3.5% in the dual antiplatelet therapy group (HR, 0.41; P = .001).
The benefit was driven by a reduced risk of major bleeding in the ticagrelor monotherapy group. At 1 year, the rate of TIMI major bleeding was 1.7% in the ticagrelor alone group vs 3% in the dual antiplatelet group (HR, 0.56; P = .02).
There was no difference in ischemic events between the two groups. The rate of death/MI/ stroke/stent thrombosis/revascularization at 1 year was 2.3% in the ticagrelor alone group vs 3.4% for those on dual antiplatelet therapy (P = .09)
Yang noted that limitations of the study included an open-label design, no placebo used, and exclusion of patients with an elevated risk for bleeding (defined as aged 80 years or older, having had a stroke within the past year, or having had brain surgery or a traumatic brain injury within the past 6 months).
As part of his discussion, Bhatt asked how these results can be reconciled with trials such as CHARISMA and PEGASUS, which showed higher rates of MI with abbreviated durations of dual antiplatelet therapy
Jang replied: “Maybe for STEMI patients, if the duration of [dual antiplatelet therapy] is prolonged ischemic events may be reduced, especially if clopidogrel is used. But my opinion is when ticagrelor or prasugrel are used — they are very strong P2Y12 inhibitors — you can reduce duration of dual therapy by dropping aspirin. I think aspirin just makes the bleeding.”
Also commenting on the TICO study, Jacqueline Tamis-Holland, MD, Mount Sinai Saint Luke’s Hospital, New York City, pointed out that there was an interaction between the number of diseased vessels, and asked for more information on the complexity of disease in the patients in this trial.
“We had very few CTOs (total chronic occlusions) and left main disease,” Jang replied. “Dual antiplatelet duration is related to total atherosclerotic burden I think, so if you have very high atherosclerotic burden and multivessel disease, dual therapy may be more important. But our data show that the ticagrelor monotherapy group is not inferior to conventional dual therapy, so this suggests that even in multivessel disease, 3 months dual antiplatelet therapy is enough if you use a potent agent like ticagrelor as monotherapy after.”
This study was funded by Biotronik, manufacturer of the stents used. Jang has disclosed no relevant financial relationships. Bhatt reports consultant fees/honoraria from Elsevier Practice Update Cardiology, Medtelligence/WebMD, MJH Life Sciences, and WebMD; and research grants from Abbott, Afimmune, Amarin, Amgen, Astra Zeneca, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, Chiesi, Eisai, Eli Lilly, Ethicon, FlowCo, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lexicon, Medtronic, Novo Nordisk, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, sanofi-aventis, Synaptic, Takeda, The Medicines Company.
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