SEOUL NATIONAL UNIVERSITY HOSPITAL

 - Longest-term and large study comparing single antiplatelet therapy in 5,438 stent patients

- Clopidogrel confirms superioity by reducing risk of thrombotic events by 31% and bleeding risk by 27% versus aspirin,

- Published in the latest issue of the international journal ‘The Lancet’... A key achievement leading the revision of global treatment guidelines

Decisive clinical results have emerged that will change the practice of taking aspirin for life after coronary stent implantation, which has been the global standard treatment for decades. Through a large-scale trial with a 10-year follow-up, the SNUH research team demonstrated the superiority of clopidogrel over aspirin as chronic single antiplatelet therapy after stent implantation. Clopidogrel significantly reduced not only overall clinical events—including death, myocardial infarction, and stroke—but also thrombotic and bleeding complications compared with aspirin.

Professor Hyo-Soo Kim of the Biomedical Research Institute at SNUH, together with Professors Ji-hoon Kang, Han-Mo Yang, and Kyung-Woo Park from the Division of Cardiology at SNUH, and Professor Sung-Jun Park from Boramae Medical Center, announced on the May 7^th that the results of the randomized clinical trial(HOST-EXAM RCT) involving 5,438 patients who underwent coronary stent implantation were published in the latest issue of The Lancet (Impact Factor = 88.5), one of the world’s most prestigious medical journals.

Ischemic heart disease occurs when coronary arteries supplying blood to the heart become narrowed. Percutaneous coronary intervention (PCI) with stent implantation is the standard treatment to reopen these narrowed vessels. Patients who undergo PCI are required to take antiplatelet medication lifelong to reduce the risk of recurrent vessel blockage.

Typically, both drugs are used together immediately after the procedure, but once the condition stabilizes, only one drug is taken for the rest of the life. Until now, international clinical guidelines have traditionally recommended aspirin as the primary single antiplatelet agent. Although the superiority of clopidogrel has recently emerged, there has been a lack of clear clinical evidence as there have been no studies tracking the long-term effects of the two drugs for more than five years.

Accordingly, the research team conducted a study involving 5,438 patients from 37 medical centers nationwide between 2014 and 2018 who had remained clinically stable without recurrent events for 6 to 18 months while maintaining dual antiplatelet therapy after coronary stent implantation. To compare the long-term efficacy of single antiplatelet therapy, the patients were randomly assigned to either an aspirin group or a clopidogrel group and were subsequently followed for 10 years.

The study demonstrated that, in the intention-to-treat (ITT) analysis including all patients originally randomized, the clopidogrel group showed superior outcomes compared with the aspirin group. The incidence of the primary endpoint—defined as a composite of all clinical events, including death, myocardial infarction, stroke, hospitalization for recurrent acute coronary syndrome, and major bleeding—was 28.5% in the aspirin group and 25.4% in the clopidogrel group. Overall, clopidogrel significantly reduced the risk of primary clinical events by 14% compared with aspirin. In addition, the clopidogrel group showed lower rates of recurrent thrombotic events and bleeding events, which were secondary endpoints of the study, while all-cause mortality did not differ between the two groups.

In particular, the rate of discontinuation of the medication due to gastrointestinal disorders or minor bleeding was higher in the aspirin group. In a per-protocol analysis of 4,179 patients who took the medication as prescribed for 10 years, excluding these patients, it was found that the clopidogrel group reduced the overall risk of clinical events by 24% compared to the aspirin group. This means that administering clopidogrel instead of aspirin for 10 years can prevent an additional 1 in 17 overall clinical events (NNT 17.3).

 

[Figure 1] Comparison of the 10-year cumulative incidence of the primary endpoint (overall clinical events) between the clopidogrel and aspirin groups (per-protocol analysis)

 

[Figure 2] Comparison of the 10-year cumulative incidence of secondary endpoints (thrombotic recurrence, bleeding events, and all-cause mortality) between the two treatment groups (per-protocol analysis)

 

When examining secondary endpoints using the same analysis criteria (protocol-compliant group), the clopidogrel group was found to significantly reduce the risk of thrombotic recurrence and bleeding by 31% and 27%, respectively. There was no difference in overall mortality rates between the two treatment groups over the 10-year period.

In conclusion, based on the 10-year long-term follow-up results, the research team emphasized that clopidogrel should be considered as a new alternative to aspirin during the maintenance phase following stent implantation.

Professor Hyo-Soo Kim said, “This study is the first large-scale randomized controlled trial over a 10-year period to compare the superiority of a single antiplatelet agent that stent implant patients take for life, and it will serve as unique clinical data that will be difficult to replace in the future.” He added, “As it has been proven that clopidogrel is superior to aspirin by lowering not only overall clinical events but also the risk of thrombosis and bleeding, I expect that global treatment guidelines will be revised soon.”

"Following The Lancet in 2021 and Circulation in 2023, this 10-year result has also been published in The Lancet, the most prestigious journal, completing unrivaled evidence," he added. "The fact that we were able to track and observe a large number of over 5,400 patients until the end over such a long period of 10 years was thanks to the dedication of the joint research team and nurses."

 

[Photo, from left] Prof. Hyo-Soo Kim(Seoul National University Hospital Biomedical Research Institute), Prof. Kyung-Woo Park, Ji-Hoon Kang, Han-Mo Yang (Division of Cardiology) and Prof. Seong-Jun Park(Division of Cardiology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center)