I’d like to contribute to this important discussion by highlighting a critical evidence gap in the treatment of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Current clinical guidelines provide detailed recommendations on the use of antithrombotic agents (e.g., aspirin, P2Y12 inhibitors) post-PCI. However, there remain unanswered questions that could be addressed with high-quality real-world evidence.
Prior landmark trials such as PLATO (2009) and TRITON-TIMI 38 (2007) established the efficacy of ticagrelor and prasugrel, respectively, compared to clopidogrel, with prasugrel demonstrating superior efficacy at the cost of increased bleeding risks. The 2021 ACC/AHA guidelines, based on these trials, include the following recommendations:
In patients with ACS undergoing PCI, it is reasonable to use ticagrelor or prasugrel in preference to clopidogrel to reduce ischemic events, including stent thrombosis (COR 2a, LOE B-R)
In patients undergoing PCI who have a history of stroke or transient ischemic attack, prasugrel should not be administered (COR 3, LOE B-R)
However, direct comparisons between prasugrel and ticagrelor remain controversial. PRAGUE-18 (2016), which demonstrated comparable composite outcomes between prasugrel and ticagrelor, was an underpowered study, limiting its reliability. ISAR-REACT 5 (2019), a sufficiently powered study that demonstrated prasugrel’s superior efficacy over ticagrelor with comparable bleeding risks, also faced criticism for potential bias.
However, the 2021 ACC/AHA guidelines did not include a recommendation on the direct comparison between ticagrelor and prasugrel due to the controversy surrounding ISAR-REACT 5, while its findings were incorporated into the 2023 ESC guidelines, in the recommendation below. These contradicting guidelines highlight a major evidence gap in this subject.
Prasugrel should be considered in preference to itcagrelor for ACS patients who proceed to PCI (Class IIa, Level B)
Furthermore, another controversy related to this subject recently flared up after the BMJ openly expressed doubts over the PLATO study (https://doi.org/10.1136/bmj.q2550). Both ACC/AHA and ESC guidelines’ current recommendations prioritizing ticagrelor are based on this trial. With the study now being directly challenged, the foundation for these recommendations may be called into question, potentially shifting the treatment landscape.
I believe a well-designed OHDSI study could provide valuable real-world evidence to address this issue.