De-Escalation of DAPT Shown to Be Safe and Effective in TALOS-AMI Study

May 16, 2021—Switching to less potent dual antiplatelet therapy (DAPT) after 30 days was safer and more effective in preventing adverse events at 1 year than continuing on a high-potency DAPT regimen in patients who had a percutaneous coronary intervention (PCI) with stenting after a heart attack. These findings from the TALOS-AMI study met the primary endpoint of a composite of death from a heart attack or stroke, a nonfatal heart attack or stroke, or bleeding requiring medical intervention at any time from 1 to 12 months after the stenting procedure.

The TALOS-AMI study evaluated the safety and efficacy of a DAPT de-escalation strategy in minimizing the risk of both another heart attack and a bleeding episode.

“We have shown that, in patients who have had a heart attack and who’ve been treated with newer-generation stents and guideline-recommended medical therapy, de-escalation of DAPT by switching from ticagrelor to clopidogrel is completely safe and more effective than continuing to treat patients with ticagrelor,” commented Kiyuk Chang, MD, the TALOS-AMI study’s lead author, in an announcement from the American College of Cardiology (ACC). Dr. Chang presented the findings at ACC’s 70th annual scientific session.

According to the ACC announcement, previous studies have shown that patients are at the highest risk for another heart attack during the first 30 days after stent insertion. Bleeding risk, by contrast, remains high during the maintenance phase of treatment after the first 30 days.

As summarized by ACC, the trial enrolled 2,697 patients from East Asia (80% men, median age 60 years) 30 days after they had undergone stenting following a heart attack. 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 heart attack, 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, a less-potent P2Y12 inhibitor, plus aspirin.

The ACC reported that at 1 year, the adverse events defined in the primary endpoint (death caused by a heart attack or stroke, a nonfatal heart attack or stroke, or bleeding requiring medical intervention) occurred in 59 (4.6%) patients in the clopidogrel group compared with 104 (8.2%) in the ticagrelor group, a statistically significant difference. Additionally, 3% of patients in the clopidogrel group experienced bleeding that required medical intervention, compared with 5.6% in the ticagrelor group, a statistically significant difference. Outcomes for arterial ischemia were similar in the two groups.

Dr. Chang stated in the ACC announcement, “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. Many cardiologists are already using DAPT de-escalation in-patient treatment, and the results of this study provide scientific evidence to justify this practice.”

Study limitations include that the trial was not blinded, and it was 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, noted Dr. Chang. “We showed 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.”

Another limitation, Dr. Chang noted, is that the overall incidence of primary endpoint events in the trial was lower than the researchers had initially estimated. In both groups, fewer patients than expected experienced arterial blockages during the study period. This finding may be explained in part by the fact that patients were randomly assigned to treatment 30 days after undergoing PCI, rather than at the time of PCI, and that all patients enrolled in the trial had received the most technologically advanced cardiac stents, which may pose a lower risk for adverse events than older devices. Additionally, a relatively large difference in the number of expected versus actual bleeding events was seen in the clopidogrel group, while in the ticagrelor group the gap between expected and observed bleeding events was smaller.

The investigators are planning to conduct a follow-up study that will examine differences in outcomes between patients similar to 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, noted the ACC announcement.