AIMS More intense platelet-directed
therapy for
acute coronary syndrome (ACS) may increase
bleeding risk. The aim of the current analysis was to determine the rate, clinical impact, and predictors of major and fatal
bleeding complications in the PLATO study. METHODS AND RESULTS PLATO was a randomized, double-blind, active control international, phase 3 clinical trial in patients with acute ST elevation and non-ST-segment elevation ACS. A total of 18 624 patients were randomized to either
ticagrelor, a non-
thienopyridine, reversibly binding platelet P2Y(12) receptor antagonist, or
clopidogrel in addition to
aspirin. Patients randomized to
ticagrelor and
clopidogrel had similar rates of PLATO major
bleeding (11.6 vs. 11.2%; P = 0.43), TIMI major
bleeding (7.9 vs. 7.7%, P = 0.56) and GUSTO severe
bleeding (2.9 vs. 3.1%, P = 0.22). Procedure-related
bleeding rates were also similar. Non-CABG major
bleeding (4.5 vs. 3.8%, P = 0.02) and non-procedure-related major
bleeding (3.1 vs. 2.3%, P = 0.05) were more common in
ticagrelor-treated patients, primarily after 30 days on treatment. Fatal
bleeding and transfusion rates did not differ between groups. There were no significant interactions for major
bleeding or combined minor plus major
bleeding between treatment groups and age ≥75 years, weight <60 kg, region,
chronic kidney disease,
creatinine clearance <60 mL/min,
aspirin dose >325 mg on the day of randomization, pre-randomization
clopidogrel administration, or
clopidogrel loading dose. CONCLUSION
Ticagrelor compared with
clopidogrel was associated with similar total major
bleeding but increased non-CABG and non-procedure-related major
bleeding, primarily after 30 days on study
drug treatment. Fatal
bleeding was low and did not differ between groups.