HOST-EXAM Compares Clopidogrel Versus Aspirin for Long-Term Maintenance After Stenting

May 16, 2021—Clopidogrel outperformed aspirin at 2-year follow-up in the HOST-EXAM randomized trial comparing the effectiveness of the two antiplatelet drugs as long-term maintenance therapy for patients who had no adverse events after 1 year of dual antiplatelet therapy (DAPT) after the insertion of a coronary stent. At 2 years, chronic maintenance therapy with clopidogrel resulted in a 30% reduction in death, heart attack, stroke, or major bleeding events.

The study’s lead investigator, Hyo-Soo Kim, MD, presented the trial findings virtually at ACC.21, the American College of Cardiology (ACC)’s 70th annual scientific sessions. The study was simultaneously published by Bon-Kwon Koo, MD, et al online in The Lancet.

The HOST-EXAM trial met its primary endpoint, a composite of death from any cause, heart attack, stroke, or major bleeding event within 2 years of study entry, which occurred in 5.7% of patients assigned to clopidogrel and 7.7% of those assigned to aspirin.

“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 1 year after coronary stenting,” commented Dr. Kim in a press release from ACC. Dr. Kim further noted, “However, the optimal single antiplatelet agent for long-term maintenance therapy beyond the duration of DAPT has been unclear.” 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.

According to the ACC announcement, the HOST-EXAM trial enrolled 5,436 patients who had received a coronary stent. The patients’ average age was 63 years; 75% were men, 34% had diabetes, and 13% had chronic kidney disease. After completing between 6 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.

In addition to the primary endpoint, the investigators separated out blood-clotting events (death, heart attack, hospital readmission because of acute coronary syndrome, or a blood clot in the stent) from all bleeding events and analyzed them as secondary endpoints. They found that blood-clotting events 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,” stated Dr. Kim in the ACC announcement. “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.”

Dr. Kim advised that the results apply only to patients who had completed between 6 and 18 months of DAPT without any adverse events. He noted, “It may be difficult to directly extrapolate our results to patients who received DAPT for a shorter period, such as 1 or 3 months. 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.”

Dr. Kim further commented in the ACC announcement that the 2 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. The investigators plan to continue follow-up for a total of 5 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, Dr. Kim said that he and his team are also planning a follow-up study that will examine the cost-effectiveness of the two medications.

Limitations of the trial included that it was not blinded and that the total number of reported adverse events in both groups was lower than the investigators expected when they designed the trial, which suggests that adverse events could have been underreported. However, the main reason for the lower-than-expected rate of adverse events was not underreporting but the quality of care that evolved over the 7-year study period, stated Dr Kim in the ACC press release.