New support for replacing higher-potency ticagrelor (Brilinta) with clopidogrel as part of dual-antiplatelet therapy (DAPT) 30 days after stenting for acute myocardial infarction comes from the TALOS-AMI trial.
“A uniform, unguided de-escalation DAPT strategy switching from ticagrelor to clopidogrel was superior to the ticagrelor-based continued DAPT strategy in terms of net clinical benefit, with a significant decrease in bleeding risk but no increase in ischemic risk,” Kiyuk Chang, MD, PhD, The Catholic University of Korea, Seoul, said at the American College of Cardiology 2021 Scientific Session (ACC.21).
Current guidelines recommend DAPT, including aspirin and a P2Y12 inhibitor like clopidogrel or ticagrelor, for 6 to 12 months after percutaneous coronary intervention (PCI). The benefit of intensive antithrombotic therapy dissipates after the first 30 days, however, and large-scale data are lacking on the optimal de-escalation strategy, he noted.
TALOS-AMI randomly assigned 2697 acute MI patients who had received 1 month of DAPT with ticagrelor and aspirin and experienced no events related to either de-escalation with aspirin and clopidogrel or continued ticagrelor and aspirin. The mean age was 60 years, 54% presented with ST-segment elevation MI, and 28% had multivessel PCI.
Adherence to antiplatelet therapy at 10 months was high, at 98.4% and 97.3% in the de-escalation and control groups, respectively.
Two weeks after randomization, there were no deaths or stent thrombosis in the de-escalation group; one patient had a non-target lesion MI unrelated to stent thrombosis at day 5. No ischemic events occurred in the control group.
The primary endpoint — a composite of cardiovascular (CV) death, MI, stroke, and Bleeding Academic Research Consortium (BARC) bleeding type 2, 3, or 5 — was reduced from 8.2% in the control group to 4.6% in the de-escalation group at 1 year (hazard ratio [HR], 0.55; 95% CI, 0.40 – 0.76; P for superiority < .001).
Results showed this was driven primarily by a reduction in BARC 2, 3, or 5 bleeding (3.0% vs 5.6%; HR, 0.52; 95% CI, 0.35 – 0.77), with similar rates of CV death, MI, and stroke (2.1% vs 3.1%; HR, 0.69; 95% CI, 0.42 – 1.14).
Limitations of the study are that it was unblinded, conducted only in South Korea, and the incidence of the primary endpoint was slightly lower than estimated, Chang said.
Although Koreans have a higher prevalence of the CYP2CI9 loss-of-function allele, which can diminish clopidogrel efficacy, “this study showed the clinical safety of switching in this population, suggesting the potential of applying this de-escalation strategy to other ethnic groups,” he said.
The trial was well done and “is going to have major implications for how we practice in taking care of our patients after acute MI,” Claire Duvernoy, MD, University of Michigan, Ann Arbor, said during a press conference. “The fact is that many of us here in the States use this strategy both for cost reasons, for tolerability reasons, and for safety reasons. And what your study has shown us is that what we are already doing in the absence of great evidence appears to be both a safe and effective strategy.”
Duvernoy was also pleased there were no signs of decreased clopidogrel efficacy in the Korean cohort and that de-escalation was not guided by platelet function testing.
“I really like the fact that you didn’t perform platelet function testing because, to be honest, that’s not done routinely in most places that I know of. And I think that gives confidence to us that it’s not something that we must be doing and must be paying attention to.”
After the presentation, primary discussant Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai, New York City, congratulated the investigators for addressing a very important question of de-escalation after acute MI, but said she was “baffled” as to why they chose to combine major hard ischemic endpoints with bleeding for the primary net clinical benefit analysis. “Are you confident that you have achieved noninferiority in the ischemic endpoints?”
Chang noted that other de-escalation antiplatelet trials have similar ischemic event rates. “So I’m sure, in terms of ischemic events, our TALOS trial shows noninferiority compared to aspirin plus ticagrelor.”
“I think that would be debatable,” Mehran countered. “We would need a much, much larger [study] given the event rates you’ve shown us. I guess in the context of other trials, maybe, and perhaps this could be an important observation to be evaluated going forward because that is the most important question.”
Mehran also questioned the low ischemic event rate and the generalizability of the results. She pointed out that a 1-month to 1-year landmark analysis from the PLATO study showed patients with acute coronary syndromes who received ticagrelor and aspirin had marked reductions in death, MI, and cerebrovascular accidents, compared with those receiving clopidogrel and aspirin.
“I saw in your slides that you felt confident that this is something that could be done uniformly but, given that this study was done in Asia where there is this Asian paradox of higher bleeding risk and lower ischemic events, how would you translate this and apply this to the population at large?” she asked.
Chang reiterated that the ischemic event rate was very similar to that reported in major de-escalation trials and said it is in line with the Asian paradox. Patients were also followed very closely at each visit for dyspnea, bleeding, and any kind of ischemic event. “Our results are fairly confident, so I’m sure these results can be applied to other ethnic groups.”
Chang reported consulting fees/honoraria from Chong Kun Dang Pharm, Medtroic Korea , and Edwards Korea ; and research grants from Abbott Korea , Medtronic Korea , and Boston Korea . Duvernoy reported having no disclosures. Mehran reported consultant fees/honoraria from Cine-Med Research Institute and Janssen Scientific Affairs; other relations with Elixir Medical, WebMD, publisher of Medscape; an ownership interest, partnership, or principal role in Applied Therapeutics, Boston Scientific, ControlRad, and STEL; and research support from Abbott, Abiomed, Arena, AstraZeneca, Bayer, Beth Israel Deaconess Medical Center, Biosensors, Boston Scientific, Bristol-Myers Squibb, Cardiawave, CERC, Chiesi, Concept Medical, CSL Behring, DSI, Medtronic, Novartis and OrbusNeich.
American College of Cardiology 2021 Scientific Session (ACC.21): Abstract 407-10. Presented May 16, 2021.
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