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Munich, Germany – 27 Aug 2018: Long-term antiplatelet monotherapy after stenting is safe but does not reduce the risk of death or heart attack compared to standard dual antiplatelet therapy, according to late breaking results from the GLOBAL LEADERS trial presented today in a Hot Line Session at ESC Congress 20181 and published in The Lancet².
Ischaemic heart disease is the top global cause of death.3 In this condition, arteries supplying oxygen-rich blood to the heart become narrowed due to the build-up of fatty material. Treatments include medication, surgery to bypass the arteries, and keyhole surgery to open clogged arteries by inserting a stent (percutaneous coronary intervention; PCI).
Among patients undergoing PCI, dual antiplatelet therapy (aspirin plus a P2Y12 inhibitor) reduces the risk of blood clots and heart attacks but also increases the risk of bleeding.4-8 A shorter duration of dual antiplatelet followed by single antiplatelet therapy with a P2Y12 inhibitor might reduce adverse events with no increase in bleeding.9
GLOBAL LEADERS is the largest trial to date testing one month of dual antiplatelet therapy versus the standard of more prolonged dual antiplatelet therapy after drug eluting stent implantation.10 The trial enrolled 15,991 patients scheduled to undergo PCI for stable coronary artery disease or acute coronary syndromes. Patients were recruited from 130 centres in 18 countries in Europe, North and South America, and Asia Pacific.
Patients underwent PCI with a drug-eluting stent, were treated with the direct thrombin inhibitor bivalirudin, and then randomly assigned in a 1:1 ratio to the experimental or standard treatment arm.
The experimental arm received one month of dual antiplatelet therapy with aspirin plus the P2Y12 inhibitor ticagrelor, followed by ticagrelor monotherapy for 23 months. The standard treatment arm received 12 months of dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor (clopidogrel for patients with stable coronary artery disease, ticagrelor for those with acute coronary syndromes), followed by aspirin monotherapy for 12 months.
Patients were followed up for the primary endpoint of all-cause death or non-fatal myocardial infarction at two years. Myocardial infarction diagnoses were confirmed by a central committee that examined electrocardiograms (ECGs) at discharge, three and 24 months. The secondary endpoint was the rate of moderate or severe bleeding (grade 3 or 5 on the Bleeding Academic Research Consortium scale) within two years.
At two years the primary endpoint had occurred in 304 (3.8%) patients in the monotherapy group and 349 (4.4%) in the standard treatment group (rate ratio [RR] 0.87, 95% confidence interval [CI] 0.75–1.01, p=0.073). All-cause mortality occurred in 224 (2.8%) patients in the monotherapy group and 253 (3.2%) in the standard treatment group (RR 0.88, 95% CI 0.74–1.06, p=0.186), and the incidence of non-fatal myocardial infarction was 1.0% versus 1.3%, respectively (RR 0.80, 95% CI 0.60–1.07, p=0.142). Rates of moderate or severe bleeding were 2.0% versus 2.1%, respectively (RR 0.97, 95% CI 0.78–1.20, p=0.766).
Professor Patrick Serruys, principal investigator, Imperial College London, UK, said: “Ticagrelor, in combination with aspirin for one month, followed by ticagrelor alone was not superior to one-year standard dual antiplatelet therapy followed by aspirin alone for reducing deaths or heart attacks during the two years after stenting.”
Professor Serruys noted that the trial was not designed to assess non-inferiority, meaning that further studies are needed to confirm that monotherapy is not less effective than extended dual antiplatelet therapy. But he said: “The risk of monotherapy compared to extended dual therapy was 0.75–1.01, suggesting that monotherapy is relatively safe.”
1“GLOBAL LEADERS TRIAL - A randomized comparison of 24 month ticagrelor and 1 month aspirin versus 12 month dual antiplatelet therapy followed by aspirin monotherapy” will be discussed during:
² The Lancet: http://dx.doi.org/10.1016/S0140-6736(18)31858-0
3World Health Organization. The top 10 causes of death 2016: http://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death.
4Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. NEJM. 2015;372:1791–1800.
5Mauri L, Kereiakes DJ, Yeh RW, et al. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. NEJM. 2014;371:2155–2166.
6Valgimigli M, Bueno H, Byrne RA, et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. Eur Heart J. 2018;39:213–260.
7Miyazaki Y, Suwannasom P, Sotomi Y, et al. Single or dual antiplatelet therapy after PCI. Nat Rev Cardiol. 2017;14:294–303.
8Capodanno D, Mehran R, Valgimigli M, et al. Aspirin-free strategies in cardiovascular disease and cardioembolic stroke prevention. Nat Rev Cardiol. 2018:15:480–496.
9Gargiulo G, Windecker S, Vranckx P, et al. A critical appraisal of aspirin in secondary prevention: Is less more? Circulation. 2016;134:1881–1906.
10Vranckx P, Valgimigli M, Windecker S, et al. Long-term ticagrelor monotherapy versus standard dual antiplatelet therapy followed by aspirin monotherapy in patients undergoing biolimus-eluting stent implantation: rationale and design of the GLOBAL LEADERS trial. EuroIntervention. 2016;12:1239–1245.
SOURCES OF FUNDING: The study was sponsored by the European Cardiovascular Research Institute (ECRI) with grants from Biosensors, AstraZeneca and the Medicines company.
DISCLOSURES: Dr. Serruys reports personal fees from Abbott Laboratories, AstraZeneca, Biotronik, Cardialysis, GLG Research, Medtronic, Sino Medical Sciences Technology, Société Europa Digital Publishing, Stentys France, Svelte Medical Systems, Philips/Volcano, St. Jude Medical, Qualimed, and Xeltis, outside the submitted work.
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