Prasugrel should be preferred over ticagrelor in acute coronary syndromes: pros and cons

Dominick J. Angiolillo¹, MD, PhD; Adnan Kastrati², MD; Marco Frazzetto³, MD; Marco Valgimigli³^,⁴^,⁵, MD, PhD

Potent inhibition of the platelet P2Y12 receptor represents a cornerstone of contemporary antithrombotic regimens in patients with acute coronary syndromes (ACS). Both prasugrel and ticagrelor have demonstrated superior efficacy compared with clopidogrel in large randomised trials and are currently recommended as first-line options in international guidelines. However, prasugrel and ticagrelor differ in terms of their pharmacological profile, evidence base, and practical aspects of use, raising the question of whether one may be preferred over the other.

Over the past decade, several studies have attempted to investigate their relative efficacy and safety in clinical practice. However, the available evidence remains inconclusive, as the limited number of head-to-head randomised trials is hampered by methodological constraints and challenges in interpretation. Moreover, differences in guideline recommendations and evolving treatment strategies (e.g., changes in pretreatment practices and shorter dual antiplatelet therapy regimens) have further complicated the interpretation of existing evidence. As such, whether prasugrel or ticagrelor should be considered the preferred P2Y12 inhibitor in unselected ACS patients remains a matter of ongoing debate.