Background: High-risk patients with STE myocardial infarction (STEMI) and cardiogenic shock were excluded from large-scale randomized studies (PLATO, TRITON) comparing clinical efficacy and safety of oral P2Y12 inhibitors.

Purpose: The study aimed to investigate impact of Killip classification on laboratory efficacy of P2Y12 inhibitors in patients with STEMI treated with primary PCI.

Methods: 429 patients with STEMI and detailed data on Killip class at presentation, who were included in the LAPCOR (Laboratory AntiPlatelet efficacy and Clinical Outcome Registry; ClinicalTrials.gov NCT02264912) registry, represent the study population. Efficacy of P2Y12 inhibitors was measured by VASP phosphorylation 24±4 hours after a loading dose of clopidogrel (600 mg, N=210), prasugrel (60 mg, N=120), or ticagrelor (180 mg, N=99) and expressed by platelet reactivity index (PRI). High on-treatment platelet reactivity HTPR was defined as PRI≥50%. Laboratory efficacy of P2Y12 inhibitors was compared between patients with (5.2% of study population; age mean (SD) 65.3 (14.8), 36.4% women) and without cardiogenic shock (age 62.5 (12.9), 30.7% women).

Results: Residual platelet reactivity was significantly higher in clopidogrel-treated patients with Killip class 4 in comparison to patients with Killip class <4 (PRI mean (SD) 61.4 (17.2)% vs. 44.4 (22.6)%, P=0.028). The significance of difference was confirmed after correction for baseline confounding characteristics (age, gender, diabetes, hypertension, renal dysfunction) with P value after adjustment=0.013. HTPR was detected in 66.7% of patients with Killip class 4 receiving clopidogrel (vs. 41.4% of Killip <4). No difference in efficacy of ticagrelor was observed between patients with and those without Killip class 4 (PRI mean (SD) 28.2 (14.4) vs. 19.0 (15.6)%, n.s.). All patients with cardiogenic shock initiated on ticagrelor had PRI<50%. In the prasugrel group, residual platelet reactivity was significantly higher in patients with Killip class 4 in comparison to patients with Killip <4 (PRI mean (SD) 35.5 (30.8)% vs. 17.6 (17.6)%, p=0.015. This difference became non-significant after adjusting for confounding variables with P value after adjustment=0.1. The probability to have HTPR in patients initiated on prasugrel with Killip class 4 did not differ significantly from those with Killip class <4 (Odds Ratio 4.6, 95% C.I. 0.8 27.3).

Conclusion: New P2Y12 receptor inhibitors are effective in patients with STEMI irrespective of Killip class at presentation. Clopidogrel should be avoided in this high-risk population, especially in patients with cardiogenic shock.