Clopidogrel (Plavix) monotherapy was superior to aspirin monotherapy for long-term post-stent maintenance in patients who had percutaneous coronary intervention (PCI), according to results of the HOST-EXAM trial.
In the multicenter study done in South Korea, the composite primary endpoint of all-cause death, MI, stroke, and Bleeding Academic Research Consortium (BARC) bleeding type ≥3 within 24 months occurred in 5.7% of those randomized to clopidogrel and 7.7% of those randomized to aspirin (HR 0.73, 95% CI 0.59-0.90).
These results were consistent across patient subgroups, regardless of baseline clinical and angiographic characteristics, reported Hyo-Soo Kim, MD, PhD, of Seoul National University Hospital, at the American College of Cardiology (ACC) virtual meeting. The results were simultaneously published in The Lancet.
In a second study at ACC, another group of South Korean researchers said that replacing higher-potency ticagrelor (Brilinta) with clopidogrel was safe in patients who underwent stenting after an MI. The TALOS-AMI study enrolled patients 30 days post-stenting. During the month post-procedure, they received dual antiplatelet therapy (DAPT) with ticagrelor plus aspirin. These patients experienced no serious adverse events (AEs) so they were randomly assigned either to continue taking ticagrelor plus aspirin daily for a year or to switch after 30 days to clopidogrel plus aspirin.
At 1 year, the AEs defined in the primary endpoint (death due to MI or stroke, a nonfatal MI or stroke, or bleeding requiring medical intervention) occurred in 59 patients in the clopidogrel group (4.6%) versus 104 in the ticagrelor group (8.2%), according to Kiyuk Chang, MD, of the Catholic University in Seoul.
Kim’s group randomized 5,530 patients from 37 centers, all of whom had been event free for 6 to 18 months after undergoing PCI and completing their prescribed DAPT. The two study groups were similar in terms of demographic, clinical, and procedural characteristics. The mean age was 63.5, and 75% of the study population was men, while 34% had diabetes and 13% had chronic kidney disease.
At the time of PCI, 25.5% had stable angina, 35.5% had angina, 19.4% had non-ST segment elevation MI (STEMI), 17.2% had STEMI, 18.3% had three-vessel disease, and 5% had left main disease.
The authors reported that the incidence of all-cause death was similar between the two trial arms at 1.9% in the clopidogrel group and 1.3% in the aspirin group.
Kim and colleagues reported 3.7% in the clopidogrel group and 5.5% in the aspirin group (HR 0.68, 95% CI 0.52-0.87) experienced the secondary composite thrombotic endpoint of cardiac death, non-fatal MI, stroke, acute coronary syndrome-related readmission, or definite or probable stent thrombosis. The number-needed-to-treat (NNT) was 51 to prevent an occurrence of a primary endpoint event and 59 to prevent a composite thrombotic endpoint event, they stated.
Any bleeding (BARC type ≥2) took place in 2.3% of the clopidogrel group and 3.3% of the aspirin group (HR 0.70, 95% CI 0.51-0.98, P=0.036), for a difference in risk of 0.9% (95% CI 0.0-1.8) and an NNT of 111 patients.
The authors also pointed out that “we found numerically more cancer-related deaths in the clopidogrel group than in the aspirin group. This finding could be due to including more patients with unknown cancer before enrolment in the clopidogrel group than in the aspirin group. The protective effect of aspirin in cancer-related death has been suggested in a few previous studies.”
“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,” Kim said at an ACC press conference. “These results confirm that clopidogrel is superior to aspirin at reducing the incidence of blood-clotting events.”
“What is interesting is that clopidogrel also performed better than aspirin at reducing bleeding events,” Kim added. “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.”
HOST-EXAM follow-up will continue until 2025, according to Kim’s group.
A study limitation was the majority East Asian patient population “who are known to have lower rates of thrombotic events compared with those of White people,” the authors noted.
In an accompanying Lancet comment, Mauro Chiarito, MD, and Giulio G. Stefanini, MD, PhD, both of Humanitas University in Milan, Italy, stated that larger studies, which include patients of different ethnicities, are necessary before “dethroning aspirin from its pivotal role in patients after PCI.”
But they acknowledged that “updated clinical practice guidelines might consider recommending clopidogrel as an effective alternative to aspirin for secondary prevention of cardiovascular disease and potentially as the drug of choice for specific patient subgroups, such as those at increased risk for gastrointestinal and intracranial bleeding.”
The study enrolled 2,697 patients, 80% of whom were male with a median age of 60. Patients were randomly assigned to 100-mg aspirin plus 75-mg clopidogrel daily or 100-mg aspirin plus 90-mg ticagrelor twice daily.
The authors reported that 3% of patients in the clopidogrel group experienced bleeding that required medical intervention versus 5.6% in the ticagrelor group, which was a statistically significant difference. Chang’s group also found that the bleeding risk was significantly greater in the ticagrelor group (P=0.001), but no difference was observed in the ischemic risk (P=0.149).
“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 dual antiplatelet therapy by switching from ticagrelor to clopidogrel is completely safe and more effective than continuing to treat patients with ticagrelor,” Chang stated.
He added that “higher-potency dual antiplatelet therapy 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…this regimen may be harmful once this early phase has passed,” adding, that “Many cardiologists are already using de-escalation in patient treatment, and the results of this study provide scientific evidence to justify this practice.”
ACC discussant Claire Duvernoy, MD, of the University of Michigan in Ann Arbor, called TALOS-MI a “well-designed, real-world study [that] is going to have major implications for the way we practice in taking care of our patients after an acute myocardial infarction. The fact is that many of us in the U.S. use this strategy…for cost reasons, for tolerability reasons, and for safety reasons.”
“Your study has shown us is that what we are already doing in the absence of great evidence appears to be both a safe and effective strategy,” she told the authors.
As for HOST-EXAM, Duvernoy called it a “very provocative and potentially practice-changing study. As most people know, aspirin has been around for hundreds of years and has been the cornerstone of our therapy in our struggle to defeat coronary artery disease. Yet we know that aspirin comes at a significant cost — it can be poorly tolerated in terms of gastrointestinal side effects [and] it has important bleeding risks, and even serious intracranial and intraocular bleeding risks. So for a long time we have been searching for a time when we can safely stop using aspirin.”
“Most of us in the United States use aspirin for long-term monotherapy after stent placement,” she added. “I think these results [with clopidogrel] could prove to be a fascinating alternative. We will have to see how widely these results can be applied.”
HOST-EXAM was funded by ChongKunDang, SamJin, HanMi, Daewoong, and the Patient-Centered Clinical Research Coordinating Center/Korea Health Technology R&D Project/South Korea Ministry of Health and Welfare. Kim disclosed relevant relationships with Medtronic, Abbott Vascular, Edwards Life Science, Boston Scientific, Terumo, Biotronik and Dio, Amgen, Pfizer, AstraZeneca, MSD, Daiichi Sankyo, and Boehringer Ingelheim.
TALOS-AMI was funded by ChongKunDang. Chang disclosed no relationships with industry.
Duvernoy disclosed no relationships with industry.