No benefit from brief DAPT followed by long-term P2Y12 inhibitor monotherapy compared with guideline recommendations
ESC 2018 - Munich
Ticagrelor monotherapy beyond one month vs. standard dual antiplatelet therapy following drug eluting stent implantation: A randomised multicentre superiority trial
Presented at the ESC congress 2018 by: PW Serruys (Rotterdam, The Netherlands)
Introduction and Methods
The P2Y12 inhibitor ticagrelor is approved on top of aspirin for the prevention of thrombotic cardiovascular events and stent thrombosis in patients with acute coronary syndromes (ACS) or a history of myocardial infarction (MI). It is hypothesized that ticagrelor may be successfully used as long-term monotherapy for patients at risk, with a lower bleeding risk and an equivalent clinical benefit.
The objective of the GLOBAL LEADERS trial was to assess whether a 1-month DAPT, followed by 23-months of ticagrelor monotherapy (experimental treatment) is superior to the traditional 12-months dual antiplatelet therapy (DAPT), followed by 12-months of aspirin monotherapy (reference treatment), in post-ACS patients and in patients with stable angina. The primary endpoint was the composite of all-cause mortality or non-fatal new Q-wave MI up to 2 years post randomization. Secondary endpoints were the components of the primary endpoint, analyzed individually.
- 15,991 patients were randomized, out of which 78% of patients in the experimental group and 93% of patients in the reference group were adherent to treatment strategies by the end of the study.
- The primary endpoint occurred in 3.81% of patients in the experimental group, and in 4.37% of patients in the reference group (HR: 0.87; 95%CI: 0.75-1.01; P=0.073).
- All-cause mortality occurred in 2.81% of patients in the experimental group, and in 3.17% in the reference group (HR: 0.88; 95%CI: 0.74-1.06; P=0.18).
- New Q-wave MI occurred in 1.04% of patients in the experimental group versus 1.29% in the reference group (HR: 0.80; 95%CI: 0.60-1.07; P=0.14).
Ticagrelor monotherapy for 23 months, after 1 month of DAPT, was not superior to the traditional 12-month DAPT, followed by 12-month aspirin monotherapy, in reducing the 2-year rate of all-cause mortality and non-fatal, new Q-wave MI, in post-ACS patients and patients with stable angina. The presenter concluded that the study shows that, having stopped aspirin 1 month post-procedure, monotherapy with the potent and consistent P2Y12 inhibitor ticagrelor is feasible, safe and potentially efficacious as compared with standard DAPT. Lack of adherence may have compromised the assessment of superiority.
After the presentation in the press conference, it was discussed that further per protocol analysis will be performed to adjust for the difference in treatment adherence between the two study groups, which was higher in the 2nd year of the study. Moreover, the study population included both ACS, as well as stable angina patients, which may have blurred the results, since stable patients do not need DAPT. This subgroup analysis is underway, and first numbers indicate that patients with elevated troponin levels, might have benefited the most from the experimental treatment.
Our reporting is based on the information provided at the ESC congress