The strengths of this current study include the randomized design and the large number of patients enrolled with adequate power to evaluate for superiority of ticagrelor compared to clopidogrel. This was a multicenter trial in Europe with 49 participating centers from France and Czech, and the interventional technique used by the operators reflects contemporary technique with 95% use of radial or ulnar access.
There are a few important points to consider in this study. First, the primary outcome was biomarker assessed myocardial necrosis and myocardial injury, and the study was not powered to assess the hard outcomes such as death and myocardial infarction. Although there have been previous reports describing the relationship between the postprocedural myocardial necrosis with worse outcomes, the definition of myocardial necrosis post-PCI and its relationship with hard outcomes remains controversial. Second, half of the patients enrolled were on chronic clopidogrel therapy which suggests that patients with inadequate platelet inhibition with clopidogrel may be under-represented in this cohort. Third, this was an open-label study and the knowledge of agent used could have affected the study results. Finally, whether the population included represents a true high-risk population is questionable. Some of the prespecified high-risk features necessary to enter the study was relatively light, such as presence of diabetes mellitus or body mass index > 30 kg/m2 compared to other criteria such as bifurcation stenting or left main stenting.
Currently, when treating patients with stable ischemic heart disease with higher risk anatomy, some operators may use ticagrelor over clopidogrel by extrapolating the study results from the ACS population. However, the results from the current study do not support the uniform use of ticagrelor in stable patients and suggests that the use of clopidogrel continues to be the standard of care. This is especially relevant considering the cost difference for the 2 agents studied. Whether there is a subgroup that benefits from ticagrelor use, such as patients with unprotected left main stenting or bifurcation stenting with 2 stent strategies, requires further investigation.
Applications for Clinical Practice
In patients presenting with stable ischemic heart disease undergoing elective PCI, ticagrelor did not lower composite of periprocedural myocardial infarction and myocardial injury at 48 hours. Clopidogrel continues to be a first line treatment after elective PCI.