The GLOBAL LEADERS ( GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation ) trial randomly assigned 15,991 patients undergoing percutaneous coronary intervention to 1-month dual antiplatelet therapy ( DAPT ) followed by 23-month Ticagrelor ( Brilique ) monotherapy or conventional 12-month DAPT followed by 12-month Aspirin ( Acetylsalicylic acid; ASA ).
Apart from Q-wave myocardial infarction, all study endpoints were analyzed as investigator reported.
This was a pre-specified ancillary study assessing whether experimental therapy is noninferior, and if met, superior, to conventional treatment for the coprimary efficacy endpoint of all-cause death, nonfatal myocardial infarction, nonfatal stroke, or urgent target vessel revascularization and superior in preventing BARC 3 ( Bleeding Academic Research Consortium ) or 5 bleeding ( coprimary safety endpoint ) at 2 years with a 0.025 significance level to preserve nominal 5% alpha error.
An independent clinical event Committee adjudicated investigator-reported and eventually unreported events of 7,585 patients from the 20 top-enrolling participating sites.
The 2-year coprimary efficacy endpoint occurred in 271 ( 7.14% ) and in 319 ( 8.41% ) patients in the experimental and conventional groups, respectively ( rate ratio [ RR ]: 0.85; 95% confidence interval [ CI ]: 0.72 to 0.99 ), fulfilling noninferiority ( p noninferiority less than 0.001 ), but not superiority ( p superiority = 0.0465 ).
The rates of BARC 3 or 5 bleeding did not differ ( RR: 1.00; 95% CI: 0.75 to 1.33; p = 0.986 ).
A time-dependent treatment effect was observed with the experimental strategy being associated with a lower risk of myocardial infarction ( RR: 0.54; 95% CI: 0.33 to 0.88; p interaction = 0.062 ) and definite stent thrombosis ( RR: 0.14; 95% CI: 0.03 to 0.63; p interaction = 0.007 ) after 1-year post-percutaneous coronary intervention.
In conclusion, Ticagrelor monotherapy after 1-month DAPT was noninferior, but not superior, to conventional treatment in the prevention of ischemic events, and it did not decrease major bleeding risk as compared with conventional treatment. ( Xagena )
Franzone A et al, J Am Coll Cardiol 2019; 74:2223-2234