GLOBAL LEADERS Trial Presented at ESC Congress

August 27, 2018—The European Society of Cardiology (ESC) announced that findings from the GLOBAL LEADERS trial demonstrated that 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 (DAPT).

The GLOBAL LEADERS trial data were presented in a Hot Line Session at the ESC Congress 2018 held August 25–29 in Munich, Germany and published by Pascal Vranckx, MD, et al online ahead of print in The Lancet.

GLOBAL LEADERS is evaluating 1 month of DAPT versus the standard of more prolonged DAPT after drug-eluting stent (DES) implantation. The study's Principal Investigator is Professor Patrick Serruys, MD, of Imperial College London, United Kingdom.

According to ESC, the trial enrolled 15,991 patients at 130 centers in 18 countries in Europe, North and South America, and Asia Pacific. Patients were scheduled to undergo percutaneous coronary intervention (PCI) for stable coronary artery disease or acute coronary syndromes.

Patients who underwent PCI with a DES 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 1 month of DAPT with aspirin plus the P2Y12 inhibitor ticagrelor, followed by ticagrelor monotherapy for 23 months.

The standard treatment arm received 12 months of DAPT 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 for the primary endpoint of all-cause death or nonfatal myocardial infarction at 2 years. Myocardial infarction diagnoses were confirmed by a central committee that examined electrocardiograms at discharge, 3 months, 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 2 years.

At 2 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 = .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 = .186), and the incidence of nonfatal myocardial infarction was 1.0% versus 1.3%, respectively (RR, 0.8; 95% CI, 0.6–1.07; P = .142). Rates of moderate or severe bleeding were 2.0% versus 2.1%, respectively (RR, 0.97; 95% CI, 0.78–1.2; P = .766).

In the ESC announcement, Prof. Serruys commented, "Ticagrelor, in combination with aspirin for 1 month, followed by ticagrelor alone was not superior to 1-year standard dual antiplatelet therapy followed by aspirin alone for reducing deaths or heart attacks during the 2 years after stenting."

Prof. Serruys noted that the trial was not designed to assess noninferiority; therefore, further studies are needed to confirm that monotherapy is not less effective than extended DAPT. However, he stated in the ESC press release, "The risk of monotherapy compared to extended dual therapy was 0.75–1.01, suggesting that monotherapy is relatively safe."