Switching from ticagrelor to clopidogrel dual antiplatelet therapy (DAPT) after 30 days was safer and more effective in preventing adverse events at one year than continuing on a high-potency DAPT regimen in patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction, according to data presented at the American College of Cardiology’s 70th Annual Scientific Session (ACC.21, 15–17 May, virtual).
“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,” said Kiyuk Chang, MD, professor of Cardiology, Division of Internal Medicine at the Catholic University of Korea in Seoul, South Korea and lead author of the study, who presented the findings at ACC.21.
The study’s primary endpoint, a composite cardiovascular death, myocardial infarction (MI), stroke and BARC bleeding type 2,3 or 5 at any time from one to 12 months after the PCI procedure, was met.
Current treatment guidelines recommend that after the insertion of a cardiac stent, patients should receive DAPT, which includes aspirin and a P2Y12 inhibitor like clopidogrel or ticagrelor, for six-to-12 months. Ticagrelor is a newer agent that, compared with clopidogrel, is more potent, faster acting and has a more predictable antiplatelet effect, but also poses a higher risk of bleeding, Chang explained. Switching between P2Y12-inhibiting medications can increase (escalate) or decrease (de-escalate) the level of P2Y12 receptor inhibition.
Previous studies have shown that patients are at the highest risk for a repeat event 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). This trial, known as TALOS-AMI, is the largest study to date to test the safety and efficacy of a DAPT de-escalation strategy in minimising the risk of both another heart attack and a bleeding episode, Chang said.
The trial enrolled 2,697 patients from East Asia (80% male, median age 60 years) 30 days after they had undergone stenting following AMI. 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.
At one year, the adverse events defined in the primary endpoint (death due to a heart attack or stroke, a nonfatal heart attack 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. Outcomes for ischaemia 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,” Chang said. “Many cardiologists are already using DAPT de-escalation in patient treatment, and the results of this study provide scientific evidence to justify this practice.”
The study findings have limitations, Chang said. The trial was not blinded, meaning that both patients and their doctors knew who was receiving which drug. Secondly, the trial 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, he said.
“However, 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,” he said.
Another limitation is that the overall incidence of primary endpoint events in the trial was lower than the researchers had initially estimated, Chang said. 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.
Chang and colleagues 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.