Safety of Crushed/Chewed P2Y12 Inhibitors in Acute Coronary Syndromes—A Meta-analysis of Randomized Controlled Trials

Background: The administration of crushed or chewed P2Y12 inhibitors (P2Y12i) allows faster platelet inhibition in patients presenting with acute coronary syndrome (ACS). Whether this administration approach is safe needs further analysis.

Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing chewed/crushed to integral P2Y12i administration in patients with ACS. Major bleeding, minor bleeding, and major adverse cardiovascular events (MACE) were analyzed as binary outcomes. Platelet reactivity unit (PRU) was assessed as a continuous outcome to estimate the impact on platelet physiology. A subgroup analysis of P2Y12i administered was performed.

Results: Nine studies comprising 1,091 patients with ACS were included; 77% were males. Overall, 87% presented with ST-segment elevation acute myocardial infarction. Six studies administered Ticagrelor, while 3 studies used Prasugrel. The crushed/chewed administration did not increase bleeding risk assessed by TIMI major and minor bleeding events (RR: 0.51, 95%CI, 0.09–2.77, p = 0.293 and RR: 0.76, 95%CI, 0.24–2.43, p = 0.542, respectively). PRU was significantly reduced within 1 hour after administration in the crushed/chewed P2Y12i group (MD: −70.0%, 95% CI, −89.0 to −51.1%, p < 0.01) while we did not observe a significant difference after 4 hours (MD: −15.1%, 95% CI −34.2 to 4.0%, p = 0.12). The type of drug did not influence the relative risk of crushed/chewed P2Y12i on major or minor bleeding (p-interaction = 0.62 and pinteraction = 0.23, respectively).

Conclusion: The crushed/chewed administration of P2Y12i in the setting of ACS appears to provide superior platelet inhibition at 1 hour without a significant impact on major or minor bleeding.

Publication History

Article published online:
11 February 2025