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In DES-PCI Era, Clopidogrel Gains Traction over Aspirin as Maintenance Monotherapy after DAPT
Korean researchers recently announced head-to-head study results that demonstrated the superiority of clopidogrel over aspirin as an antiplatelet monotherapy after coronary stenting and dual antiplatelet therapy (DAPT). The investigator-initiated HOST-EXAM1 findings were published in The Lancet on May 16 and simultaneously presented by Hyo-soo Kim, MD, PhD (Seoul National University Hospital, Seoul, South Korea) at the annual American College of Cardiology Scientific Sessions (ACC 2021) last month. The study reported a 30% reduction in deaths, heart attacks, strokes, or major bleeding events with clopidogrel monotherapy than aspirin in patients who had undergone percutaneous coronary intervention (PCI) with drug-eluting stents (DES) without experiencing adverse events during 6 to 18 months of DAPT. Findings also showed clopidogrel monotherapy decreased both the risk of thrombotic and bleeding events compared to aspirin alone. "These data confirm our working hypothesis that long-term maintenance antiplatelet monotherapy with clopidogrel produces better outcomes than aspirin in patients who are free from adverse events at 1-year following coronary stenting," Kim said. The findings break away from current recommendations by both the 2016 American College of Cardiology/American Heart Association (ACC/AHA) and the 2017 European Society of Cardiology/ European Association for Cardio-Thoracic Surgery (ESC/EACTS) guidelines that recommend aspirin as the standard maintenance monotherapy after DAPT. Although aspirin has been the mainstream treatment for secondary prevention of ischemic events in the patient group, previous studies such as the CAPRIE trial2 (conducted in the "pre-DES" era) on nearly 20,000 patients had already begun to show significant benefits of long-term clopidogrel over aspirin monotherapy. Nearly 20 years later - with clopidogrel no longer a "new" antiplatelet in the market - observational findings3 by Korean researchers led by Tae-kyu Park, MD (Samsung Medical Center, Seoul, South Korea) also hinted at benefits of clopidogrel over aspirin to prevent ischemic events. Although Park and colleagues found positive findings of clopidogrel monotherapy in the era of drug-eluting stents, they called for further randomized trials - noting the lack of studies comparing outcomes of different antiplatelet monotherapies for DES-PCIs. At ACC 2021, Kim likewise noted that "[despite guidelines recommendations,] the optimal single antiplatelet agent for long-term maintenance therapy beyond the DAPT duration has been unclear," adding that physicians in clinical practice are still extending DAPT for as long as 18 months depending on the patient's bleeding risk. The prospective randomized open-label multicenter HOST-EXAM trial conducted across 37 study sites in Korea from March 2014 to May 2018 enrolled and randomized 5,438 patients (avg. age 63 years; 75% men) who had received DES-PCI and went through 6 to 18 months of DAPT therapy without experiencing clinical events. Patients were randomized to receive either clopidogrel monotherapy 75 mg once daily (n=2,710) or aspirin 100 mg once daily (n=2,728), and final analyses were completed in 98.2% (5,338 patients) over 24 months. The primary endpoint was defined as the composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome (ACS), and Bleeding Academic Research Consortium (BARC) type bleeding ≥3. Secondary thrombotic endpoints were defined as composite events of cardiac death, non-fatal MI, ischemic stroke, ACS-related readmission, or stent thrombosis. Results showed the primary outcome decreased by 27% in the clopidogrel arm over the aspirin arm (5.7% vs. 7.7%, HR 0.73, 95% CI 0.59-0.90, p=0.0035). Secondary endpoint data also favored clopidogrel over aspirin, with thrombotic events occurring in 3.7% of the clopidogrel arm and 5.5% of the aspirin arm (HR 0.68, 95% CI, 0.52-0.87, p=0.0028). All bleeding events (BARC type≥2) occurred in 2.3% of the clopidogrel group and 3.3% of the aspirin group (HR 0.70, p=0.036). Study investigators concluded that clopidogrel monotherapy "significantly reduced" the risk of primary endpoint incidence, suggesting its superiority for preventing adverse clinical events in the population. "These results confirm that clopidogrel is superior to aspirin for reducing blood-clotting events incidence," Kim said. "What is striking is that clopidogrel also fared better than aspirin at reducing bleeding events." "Such findings that one antiplatelet agent is better than the other for both clotting and bleeding events have been observed in other studies, suggesting that thrombotic and bleeding events are closely associated [especially when considering] patients [discontinue] antiplatelet agents after experiencing bleeding, which ultimately results in thrombotic events," he added. However, Kim warned that these results could only be generalized to patients who have taken long-term DAPT without adverse events: "It may be difficult to extrapolate our results to patients who have received DAPT for a shorter period such as 1 or 3 months, but these results may help physicians select an antiplatelet monotherapy for patients in a chronic stable phase after stenting." Limitations include that the study was not blinded and comprised of a Korean population only, as well as a lower-than-expected number of adverse events reported in both groups. Kim and colleagues said follow-up would be extended to more than 5 years to track long-term outcomes and further understand clopidogrel's safety and efficacy over aspirin. The research team will also run a separate cost-effectiveness study regarding the two medications, noting that clopidogrel costs more than aspirin. The study was funded by the Korea’s Ministry of Health and Welfare and four Korean pharmaceutical firms of Chong Kun Dang, Samjin, Hanmi, and Daewoong. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01063-1/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(96)09457-3/fulltext https://www.ahajournals.org/doi/full/10.1161/CIRCINTERVENTIONS.115.002816
June 21, 2021 9753
