While long-term antiplatelet monotherapy after drug-eluting stent implantation is safe, it does not reduce the risk of death or heart attack compared to standard dual antiplatelet therapy (DAPT), based on results from the GLOBAL LEADERS Trial presented Aug. 27 at ESC Congress 2018 and simultaneously published in The Lancet. The trial is the largest to date testing one month of DAPT followed by monotherapy vs. the standard treatment of one-year DAPT followed by aspirin.

GLOBAL LEADERS enrolled 15,991 patients scheduled to undergo PCI with a drug-eluting stent for stable coronary artery disease (CAD) or acute coronary syndromes (ACS). Patients were recruited from 130 centres in 18 countries in Europe, North and South America, and Asia Pacific. Following PCI, patients were randomized (1:1 ratio) to receive either experimental or standard care. The experimental arm was assigned to one month of DAPT with aspirin plus ticagrelor, followed by ticagrelor monotherapy for 23 months. Standard treatment included 12 months DAPT with aspirin plus clopidogrel (stable CAD patients) or ticagrelor (ACS patients), followed by aspirin monotherapy for 12 months. The primary endpoint was all-cause death or non-fatal myocardial infarction at two years, with a secondary endpoint being the rate of moderate or severe bleeding within two years.

Overall results found the primary endpoint had occurred in 304 patients (3.8 percent) in the experimental group and 349 patients (4.4 patients) in the standard treatment group. All-cause mortality occurred in 2.8 percent of patients in the experimental group and 3.2 percent in the standard treatment group. Rates of moderate or severe bleeding were similar between both the experimental and standard care groups (2.0 percent vs. 2.1 percent, respectively.

Principal Study Investigator Patrick Serruys, MD, FACC, of Imperial College London, UK, noted that the trial was not designed to assess non-inferiority and that further studies are needed to confirm that monotherapy is not less effective than extended DAPT. However, he said: "The risk of monotherapy compared to extended dual therapy was 0.75–1.01, suggesting that monotherapy is relatively safe."

Serruys and his colleagues say the trial results do not support a change in practice at this time. In a related editorial comment also published in The Lancet, Deepak L. Bhatt, MD, MPH, FACC, agrees. However, he also writes: "Several trials are underway to establish whether the duration of DAPT after elective stenting can be shortened. The best way to optimize the balance between reduction of the risk of ischemic events and avoidance of bleeding risk could be to use biological assays or simple risk scores to establish the ideal intensity and duration of antithrombotic therapy in individual patients. Thus, the field of tailoring therapy remains ripe for investigation."

Clinical Topics: Acute Coronary Syndromes

Keywords: ESC18, ESC Congress, Acute Coronary Syndrome, Aspirin, Adenosine, Platelet Aggregation Inhibitors

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