Aspects of dual antiplatelet therapy (DAPT) were the focus of two separate Late-Breaking Clinical Trials out of South Korea – TALOS-AMI and HOST-EXAM – that were presented May 16 during ACC.21.

The TALOS-AMI study enrolled 2,697 patients from East Asia (80% male, median age 60 years) 30 days after they had undergone stenting following a myocardial infarction (MI). During the month after their procedure, all patients had received DAPT with ticagrelor plus aspirin and had experienced no serious adverse events such as another MI, stroke or major bleeding. Patients were randomly assigned either to continue taking ticagrelor plus aspirin daily for a year or to switch after 30 days to clopidogrel plus aspirin.

At one year, the adverse events defined in the primary endpoint (death due to MI or stroke, a nonfatal MI or stroke, or bleeding requiring medical intervention) occurred in 59 patients in the clopidogrel group (4.6%) compared with 104 in the ticagrelor group (8.2%), a statistically significant difference. Three percent of patients in the clopidogrel group experienced bleeding that required medical intervention, compared with 5.6% in the ticagrelor group, also a statistically significant difference. Rates of ischemia were similar in the two groups.

"We found that the higher-potency DAPT regimen with ticagrelor was needed only during the first 30 days after a heart attack, when the risks of another heart attack or arterial blockage are highest, and that this regimen may be harmful once this early phase has passed," said Kiyuk Chang, MD, lead author of the study. "Many cardiologists are already using DAPT de-escalation in patient treatment, and the results of this study provide scientific evidence to justify this practice."

TALOS-AMI did have limitations, including being unblinded and conducted only in South Korea. A genetic variant that reduces the effectiveness of clopidogrel occurs significantly more frequently in people of East Asian ethnicity than in other ethnic groups, Chang said. However, he noted that the findings show "the clinical safety and efficacy of switching from ticagrelor to clopidogrel in an East Asian population, which suggests that this de-escalation strategy could be safely applied to clinically similar patients of other ethnicities."

Chang and colleagues are planning to conduct a follow-up study that will examine differences in outcomes between patients similar with those enrolled in the TALOS-AMI trial who are or are not treated with the DAPT de-escalation strategy in the "real world" outside of a clinical trial setting.

Meanwhile, in the HOST-EXAM trial, the findings of which were simultaneously published in The Lancet, clopidogrel monotherapy was superior to aspirin monotherapy for long-term post-stent maintenance therapy for patients with no adverse events after 12 months of DAPT. After two years of follow-up, chronic maintenance therapy with clopidogrel resulted in a 30% reduction in deaths, MI, stroke, readmission due to acute coronary syndrome, or major bleeding events.

Researchers randomly assigned 5,438 patients who had received a coronary stent and completed between six and 18 months of DAPT without experiencing any adverse events to either the clopidogrel group (75 mg once daily) or the aspirin group (100 mg once daily) for 24 months. Patients' average age was 63 years; 75% were men, 34% had diabetes and 13% had chronic kidney disease.

Overall, the trial met its primary endpoint, a composite of death from any cause, MI, stroke or a major bleeding event within two years of study entry, which occurred in 5.7% of patients assigned to clopidogrel and 7.7% of those assigned to aspirin.

"These results confirm that clopidogrel is superior to aspirin at reducing the incidence of blood-clotting events," said Hyo-Soo Kim, MD, PhD, professor of internal medicine at Seoul National University Hospital in South Korea and lead author of the study. "What is interesting is that clopidogrel also performed better than aspirin at reducing bleeding events. Such findings that one antiplatelet agent is better than the other in reducing both clotting and bleeding events have been observed in other studies comparing different antiplatelet regimens, suggesting that thrombotic and bleeding events are tightly associated with each other. For example, when patients experience bleeding, they stop the antiplatelet agents leading [them to experience] thrombotic events."

Kim said that the results apply only to patients who had completed between six and 18 months of DAPT without any adverse events and noted that it "may be difficult to directly extrapolate our results to patients who received DAPT for a shorter period, such as one or three months." However, he said the results "may be useful in helping physicians to select antiplatelet monotherapy for patients who are in the chronic stable phase after coronary stenting."

Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Interventions and ACS, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: ACC Annual Scientific Session, ACC21, Myocardial Infarction, Percutaneous Coronary Intervention, Angiography, Acute Coronary Syndrome, Aspirin, ACC International

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