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

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.

Antithrombotic therapy of patients with atrial fibrillation discharged after major non-cardiac surgery. 1-year follow-up. Sub-analysis of PRAGUE 14 study.

BACKGROUND: The study investigated the discharge antithrombotic medication in patients with atrial fibrillation (AF) after major non-cardiac surgery and the impact on one-year outcomes. METHODS: A subgroup of 366 patients (mean age 75.9±10.5 years, women 42.3%, acute surgery 42.9%) undergoing major non-cardiac surgery and having any form of AF (30.6% of the total population enrolled in the PRAGUE-14 study) was followed for 1 year. RESULTS: Antithrombotics (interrupted due to surgery) were resumed until discharge in 51.8% of patients; less frequently in men (OR 0.6 (95% CI 0.95 to 0.35); p = 0.029), and in patients undergoing elective surgery (OR 0.6 (95% CI 0.91 to 0.33); p = 0.021). Dual antiplatelet therapy was resumed more often (91.7%) in comparison to aspirin monotherapy (57.3%; p = 0.047), and vitamin K antagonist (56.3%; p = 0.042). Patients with AF had significantly higher one-year mortality (22.1%) than patients without AF (14.1%, p = 0.001). The causes of death were: ischaemic events (32.6% of deaths), bleeding events (8.1%), others (N = 51; 59.3%, 20 of them died due to cancer). Non-reinstitution of aspirin until discharge was associated with higher one-year mortality (17.6% vs. 34.8%; p = 0.018). CONCLUSION: Preoperatively interrupted antithrombotics were re-administrated at discharge only in half of patients with AF, less likely in male patients and those undergoing elective surgery. The presence of AF was recognized as a predictor of one-year mortality, especially if aspirin therapy was not resumed until discharge. TRIAL REGISTRATION: ClinicalTrials.gov NCT01897220.

Selection of P2Y12 antagonist, treatment initiation, and predictors of high on-treatment platelet reactivity in a "Real World" registry.

OBJECTIVE: The present study aimed to compare characteristics related to selection of a P2Y12 antagonist, investigate initiation of therapy with new-generation drugs, and identify predictors of high on-treatment platelet reactivity (HTPR) in patients with acute coronary syndrome treated with stent percutaneous coronary intervention (PCI). METHODS AND RESULTS: Data from 589 patients in the LAPCOR (Laboratory AntiPlatelet efficacy and Clinical Outcome Registry; ClinicalTrials.gov Identifier: NCT02264912) registry was analyzed. P2Y12 receptor antagonist efficacy was measured by VASP phosphorylation 24 ± 4 hours after a loading dose of clopidogrel (600 mg, N=407), prasugrel (60 mg, N=106), or ticagrelor (180 mg, N=76) and expressed by platelet reactivity index (PRI). HTPR was defined as PRI ≥50%. Patients treated with prasugrel were significantly younger and had significantly higher hemoglobin levels than those who received clopidogrel or ticagrelor, while chronic kidney disease was significantly more prevalent in the ticagrelor group. Almost all invasively managed patients given new-generation drugs received a loading dose after coronary angiography. Mean residual PRI and HTPR were significantly higher after clopidogrel (44.2 ± 23.1% and 42.2%, respectively) vs. prasugrel (17.7 ± 18.0% and 9.4%, respectively) or ticagrelor (18.8 ± 17.0% and 7.9%, respectively; all p<0.001). Among multiple variables tested, HTPR in patients treated with the new agents significantly related only to platelet count (p=0.014) and mean platelet volume (p=0.03). CONCLUSION: Safety is the most important aspect under consideration in choosing new agents for an individual patient. Other than platelet count and mean platelet volume, factors known as predictors of higher platelet reactivity, did not influence the efficacy of new-generation P2Y12 receptor antagonists.

Severe left ventricular systolic dysfunction is independently associated with high on-clopidogrel platelet reactivity.

OBJECTIVE: The purpose of the present study was to investigate the association between left ventricular systolic function and the response to clopidogrel. METHODS: The efficacy of clopidogrel was measured by the vasodilator-stimulated phosphoprotein phosphorylation 20 ± 4 h after 600 mg of clopidogrel. High on-clopidogrel platelet reactivity (HCPR) was defined as a platelet reactivity index (PRI) ≥50%. The 30-day combined incidence of death, non-fatal acute coronary syndrome, re-percutaneous coronary intervention (PCI), stent thrombosis, and stroke was also investigated. RESULTS: The study group consisted of 519 patients undergoing PCI. The values (mean and 95% confidence interval) of the PRI were as follows: 40.4% (37.8-43.0) in patients with left ventricular ejection fraction (LVEF) >50%, 42.4% (39.3-45.6) in patients with LVEF 35-50%, and 46.7% (40.6-52.9) in patients with LVEF <35% (p = 0.013). The proportions of patients with HCPR were 35.9% in patients with LVEF ≥35 and 51.9% in patients with LVEF <35% (p = 0.022). After adjustment for variables that significantly influenced clopidogrel efficacy, LVEF <35% was found to be independently associated with HCPR (p = 0.039). The 30-day combined clinical endpoint occurred in 18% of patients with LVEF <35% and in 7.3% of patients with LVEF ≥35% (p = 0.026). The 30-day incidence of all-cause mortality was 14% in patients with LVEF <35 and 1.0% in patients with LVEF ≥35% (p < 0.001). CONCLUSION: An LVEF <35% was found to be independently associated with HCPR.