BACKGROUND: Percutaneous coronary intervention (PCI)-related myonecrosis is 
frequent and can affect the long-term prognosis of patients. To our knowledge, 
ticagrelor has not been evaluated in elective PCI and could reduce 
periprocedural ischaemic complications compared with clopidogrel, the currently 
recommended treatment. The aim of the ALPHEUS study was to examine if ticagrelor 
was superior to clopidogrel in reducing periprocedural myocardial necrosis in 
stable coronary patients undergoing high-risk elective PCI.
METHODS: The ALPHEUS study, a phase 3b, randomised, open-label trial, was done 
at 49 hospitals in France and Czech Republic. Patients with stable coronary 
artery disease were eligible for the study if they had an indication for PCI and 
at least one high-risk characteristic. Eligible patients were randomly assigned 
(1:1) to either ticagrelor (180 mg loading dose, 90 mg twice daily thereafter 
for 30 days) or clopidogrel (300-600 mg loading dose, 75 mg daily thereafter for 
30 days) by use of an interactive web response system, and stratified by centre. 
The primary outcome was a composite of PCI-related type 4 (a or b) myocardial 
infarction or major myocardial injury and the primary safety outcome was major 
bleeding, both of which were evaluated within 48 h of PCI (or at hospital 
discharge if earlier). The primary analysis was based on all events that 
occurred in the intention-to-treat population. The trial was registered with 
ClinicalTrials.gov, NCT02617290.
FINDINGS: Between Jan 9, 2017, and May 28, 2020, 1910 patients were randomly 
assigned at 49 sites, 956 to the ticagrelor group and 954 to the clopidogrel 
group. 15 patients were excluded from the ticagrelor group and 12 from the 
clopidogrel group. At 48 h, the primary outcome was observed in 334 (35%) of 941 
patients in the ticagrelor group and 341 (36%) of 942 patients in the 
clopidogrel group (odds ratio [OR] 0·97, 95% CI 0·80-1·17; p=0·75). The primary 
safety outcome did not differ between the two groups, but minor bleeding events 
were more frequently observed with ticagrelor than clopidogrel at 30 days (105 
[11%] of 941 patients in the ticagrelor group vs 71 [8%] of 942 patients in the 
clopidogrel group; OR 1·54, 95% CI 1·12-2·11; p=0·0070).
INTERPRETATION: Ticagrelor was not superior to clopidogrel in reducing 
periprocedural myocardial necrosis after elective PCI and did not cause an 
increase in major bleeding, but did increase the rate of minor bleeding at 30 
days. These results support the use of clopidogrel as the standard of care for 
elective PCI.
FUNDING: ACTION Study Group and AstraZeneca.