Safety of crushed/chewed P2Y12 inhibitors in acute coronary syndromes - a meta-analysis of randomized controlled trials.

The administration of crushed or chewed P2Y12 inhibitors (P2Y12i) allows faster platelet inhibition in patients presenting acute coronary syndrome (ACS). Whether this administration approach is safe needs further analysis. 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. Nine studies comprising 1091 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 absolute risk of bleeding, assessed by TIMI, was low in both intervention and control arms (0.36% vs. 0.95% for major bleedings and 3.3% vs. 4.4% for minor bleedings), and crushed/chewed administration did not increase the relative risk of bleeding events for TIMI major or minor bleedings (RR 0.51, 95% CI 0.09-2.77, p = 0.293; RR 0.76, 95% CI 0.24-2.43, p = 0.542) or MACE (RR 0.94, 95% CI 0.28-3.19, p = 0.902). PRU was significantly reduced within 1 h 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 h (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 p_interaction = 0.23_, respectively). The crushed/chewed administration of P2Y12i in the setting of ACS was not associated with an increased risk of bleeding, suggesting the safety of this strategy.