- Clopidogrel is superior to aspirin as chronic maintenance therapy after drug eluting stent (DES) placement with contemporary percutaneous coronary intervention (PCI) following 12 ± 6 months of dual antiplatelet therapy (DAPT)
- Specifically, those on Clopidogrel had a reduction in the composite endpoint of myocardial infarction, stroke, readmission for ACS as well was the secondary endpoints of thrombotic and bleeding events
The field of interventional cardiology has progressed significantly since the first coronary stent was deployed over forty years ago. Drug eluting stents have revolutionized our treatment of acute coronary syndrome and medical management following coronary intervention continues to be refined. While clinical practice has been to place patients on dual antiplatelet therapy (DAPT) post intervention, the optimal antiplatelet therapy regiment as well as duration remains uncertain.
Previous work from the CAPRIE trial (https://pubmed.ncbi.nlm.nih.gov/16749646/) in 2006 has suggested that clopidogrel monotherapy in patients with atherosclerotic disease have a decreased risk of ischemic stroke, myocardial infraction or vascular death compared with aspirin. However, given improvements in medications, DES technology, and PCI technique, contemporary data is needed.
In this prospective, open label, randomized, comparative effectiveness trial, Dr. Hyo-Soo Kim, MD, PhD, Professor, Department of Internal Medicine, Cardiovascular Center, Seoul National University Hospital, and his colleagues examined long term monotherapy (aspirin 100 mg vs clopidogrel 75 mg) in 5530 patients enrolled at 37 centers in Korea over the period of two years. Primary endpoints included rate of clinical events defined as a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, or major bleeding at 24 months after randomization. Results released on Day 2 of ACC 2021 showed the event rate was 7.7% in the aspirin group compared to 5.7% in the clopidogrel group (hazard ratio of 0.73 with confidence interval of 0.59-0.90, P=0.03) Clopidogrel was also superior to aspirin in meeting secondary endpoints including bleeding and thrombotic events.
Limitations of the trial included its open label design, leaving room for possible selection and ascertainment bias. In addition, the observed event rate for aspirin was lower than expected (7.7% for 2 years). When asked about this, Dr Kim remarked this was likely due to the evolution of modern medicine, as the event rate was extrapolated from the CAPRIE trial which was published 26 years ago. In addition, eligibility for enrollment included only patients who were event free after 12 months of DAPT. This makes it difficult to extrapolate data for those who only underwent DAPT for a shorter period of time, as Dr Kim speculates the vascular biology may be stabilized beyond 1-3 months. Genetic testing for CYP2C19 was not performed.
While this trial underscores the benefit of clopidogrel as monotherapy beyond DAPT 12 months after DES, what about the cost implication? While it was not clinically significant, Dr Kim and his colleagues noted a lower number of deaths in aspirin group than the clopidogrel group. While the issue of aspirin and incidence of cancer and cancer death remains, death is a serious cost event when completing a cost effectiveness analysis; thus, a lower death rate in the aspirin group may continue to favor aspirin despite the reduced event rates from clopidogrel. Dr. Kim stated. “The cost effectiveness of clopidogrel is not so simple, but it is clear that based on this trial, this is the first evidence to support physicians’ practice of clopidogrel monotherapy beyond DAPT.”
HOST-EXAM was sponsored by Seoul National University Hospital. ClinicalTrials.gov number, NCT02044250.