Clopidogrel monotherapy produced better outcomes than aspirin for the long-term maintenance of patients who had undergone percutaneous coronary intervention (PCI) with a drug-eluting stent (DES). This is according to findings of HOST-EXAM, an investigator-initiated, randomised, open-label, multicentre trial, which sought to examine the optimal choice of antiplatelet agent during the chronic maintenance period following PCI.
Findings from HOST-EXAM were presented at the American College of Cardiology’s 70th Annual Scientific Session (ACC.21, 15–17 May, virtual) during a late-breaking trial session, and simultaneously published in The Lancet.
Lead investigator Hyo-Soo Kim (Seoul National University Hospital, Seoul, Korea) told ACC.21 attendees that clopidogrel monotherapy significantly reduced the risk of the composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and BARC bleeding type 3 or greater, as compared to aspirin monotherapy. The beneficial effect of clopidogrel was also observed in thrombotic composite endpoints, as well as any bleeding endpoint, Kim explained.
“These data confirm our working hypothesis that long-term maintenance antiplatelet monotherapy with clopidogrel produces better outcomes than aspirin in patients who are adverse event-free at one year after coronary stenting,” said Kim.
The trial met its primary endpoint, a composite of death from any cause, non-fatal myocardial infarction (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.
Current treatment guidelines recommend a dual antiplatelet therapy (DAPT) regimen of two antiplatelet drugs for six to 12 months after the insertion of a coronary stent to prevent blood clots.
“However, the optimal single antiplatelet agent for long-term maintenance therapy beyond the duration of DAPT has been unclear,” Kim said. He added that in clinical practice, physicians may maintain patients on DAPT for as long as 18 months, depending on the patients’ level of risk for clotting.
HOST-EXAM enrolled 5,436 patients from 37 centres in Korea who had received a coronary stent. Patients’ average age was 63 years; 75% were men, 34% had diabetes and 13% had chronic kidney disease. After completing between six and 18 months of DAPT without experiencing any adverse events, patients were randomly assigned to receive single-agent maintenance therapy with either clopidogrel or aspirin.
Researchers also assessed key secondary endpoints, including thrombotic composite endpoints of cardiac death, non-fatal myocardial infarction, ischaemic stroke, readmission due to acute coronary syndrome and stent thrombosis. They found that these secondary endpoints occurred in 3.8% of the patients who took clopidogrel compared with 5.6% of those who took aspirin; bleeding events were seen in 2.3% of patients in the clopidogrel group versus 3.3% of those in the aspirin group. All of the differences between the groups were statistically significant.
“These results confirm that clopidogrel is superior to aspirin at reducing the incidence of blood-clotting events,” Kim said. “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.
“It may be difficult to directly extrapolate our results to patients who received DAPT for a shorter period, such as one or three months,” he said. “However, our results may be useful in helping physicians to select antiplatelet monotherapy for patients who are in the chronic stable phase after coronary stenting.”
The two years of patient follow-up in the HOST-EXAM trial is longer than that of many previous trials comparing antiplatelet drug regimens in patients who have received a coronary stent, Kim said. He and his colleagues plan to continue their follow-up for a total of five years to gain further insights into the long-term benefits and trade-offs of clopidogrel compared with aspirin. Because the daily cost of clopidogrel is higher than that of aspirin, Kim said, he and his team are also planning a follow-up study that will examine the cost-effectiveness of the two medications.
Another limitation is that the trial was not blinded, meaning that both patients and their doctors knew which drug patients were receiving. Also, the total number of reported adverse events in both groups was lower than the investigators had expected when they designed the trial, which suggests that adverse events could have been under-reported. However, Kim said that the expected event rate was based on CAPRIE study 26 years ago and his GRAND-DES registry paper 10 years ago and thus he believes the main reason for the lower than expected rate of adverse events was not under-reporting, but the improved quality of care that has evolved over recent decades.