Antiplatelet efficacy of P2Y12 inhibitors (prasugrel, ticagrelor, clopidogrel) in patients treated with mild therapeutic hypothermia after cardiac arrest due to acute myocardial infarction

Abstract

Survivors after cardiac arrest (CA) due to AMI undergo PCI and then receive dual antiplatelet therapy. Mild therapeutic hypothermia (MTH) is recommended for unconscious patients after CA to improve neurological outcomes. MTH can attenuate the effectiveness of P2Y12 inhibitors by reducing gastrointestinal absorption and metabolic activation. The combined effect of these conditions on the efficacy of P2Y12 inhibitors is unknown. We compared the antiplatelet efficacies of new P2Y12 inhibitors in AMI patients after CA treated with MTH. Forty patients after CA for AMI treated with MTH and received one P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor) were enrolled in a prospective observational single-center study. Platelet inhibition was measured by VASP (PRI) on days 1, 2, and 3 after drug administration. In-hospital clinical data and 1-year survival data were obtained. The proportion of patients with ineffective platelet inhibition (PRI > 50 %, high on-treatment platelet reactivity) for clopidogrel, prasugrel, and ticagrelor was 77 vs. 19 vs. 1 % on day 1; 77 vs. 17 vs. 0 % on day 2; and 85 vs. 6 vs. 0 % on day 3 (P < 0.001). The platelet inhibition was significantly worse in clopidogrel group than in prasugrel or ticagrelor group. Prasugrel and ticagrelor are very effective for platelet inhibition in patients treated with MTH after CA due to AMI, but clopidogrel is not. Using prasugrel or ticagrelor seems to be a more suitable option in this high-risk group of acute patients.

Prasugrel Versus Ticagrelor in Patients With Acute Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention

“…Our previous study documented strong and comparable antiplatelet efficacy for prasugrel and ticagrelor in the vast majority of patients with AMI after out-of-hospital cardiac arrest who were treated with mild therapeutic hypothermia. 24 Patients with cardiogenic shock are generally not included in randomized, clinical studies, and reported results on the efficacy and safety of the medications are very rare in this group of patients. Unfortunately, the results of the PRAGUE-18 study, given the small number of patients enrolled, cannot offer relevant arguments on the differences between benefits and risks of newer drugs for subgroups of patients.…”

Effectiveness of Antiplatelet Drugs Under Therapeutic Hypothermia: A Comprehensive Review

“…The vast majority of studies were conducted under moderate TH (33°C) that lasted 24 hours, whereas mild (36°C) TH or different duration of TH was investigated to a lesser extent. Although some discrepancies exist among the published results, most studies demonstrate that moderate TH reduces P2Y 12 ‐mediated platelet inhibitory effect …”

“…Briefly, the study showed that prasugrel and ticagrelor are highly effective in platelet inhibition in patients treated with mild TH after CA due to AMI but clopidogrel is not. It may suggest that administration of prasugrel or ticagrelor seems to be a more suitable option in this high‐risk group of acute patients …”

“…It may suggest that administration of prasugrel or ticagrelor seems to be a more suitable option in this high-risk group of acute patients. 68…”

“…Although some discrepancies exist among the published results, most studies demonstrate that moderate TH reduces P2Y 12 -mediated platelet inhibitory effect. 62,63,67,68,73,75…”