Abstract 4018: The Comparison of Clopidogrel Effectiveness in Patients with Hemodynamically Stable vs. Unstable Acute Myocardial Infarction

Abstract

Clopidogrel represents the standard of care in patients with ST-elevation myocardial infarction (STEMI) treated by primary PCI. However, as a prodrug, it has to be metabolized to the active form in the liver. Furthermore, this drug exists in oral form only and sufficient absorption from gastrointestinal tract is needed. We hypothezied, clopidogrel efficacy might be lower in patients with severe hemodynamic instability, where splanchnic and liver ischemia is present. Forty patients with STEMI were enrolled in the prospective, case-control designed study. Twenty (unstable) were in severe hemodynamical instability (cardiogenic shock (n=8), severe pulmonary oedema (n=4), prolonged resuscitation due to arrhythmias (n=8)). All of them were on mechanical ventilation and catelcholamine support on admission (inclusion criteria=MI, mechanical ventilation, catecholamine support). The other 20 patients (stable) served stbale (Killip I) cross-matched control. All 40 patients were treated by PCI. Blood samples were drawn before (baseline), 4h (4h+), 24h (1d+) and 2 days (2d+) after clopidogrel administration. Clopidogrel efficacy was assessed by measurement of Vasodilator-Stimulated Phosphoprotein phosphorylation (VASP-P) using flow cytometry. Unstable patients had higher lactate level (5.4+4.8 vs. 1.7+0.6, p=0.009) on admission and also higher markers of liver dysfunction (INR at 1d+: 1.1+0.1 vs. 1.5+0.4, p<0.01). However, the ejection fraction of left ventricle (44.5+9.1 vs. 36.0+15.8, p=0.1) and peak troponin levels were not different between both groups- The decrease of VASP-P was substantially lower in unstable patients compared with stable ones (ANOVA, p<0.05). In stable patients and compared with baseline, the VASP-P decreased significantly by 22% at 4h+ and by 34% at 1d+, and remaiend decreased by 34% at 2d+ (all p<0.05). In unstable patients, the VASP-P decreased nonsignificantly by 5% at 4h+, and no further decrease of VASP-P was present (−2.4% at 1d+, −6% at 2d+; all p=n.s.). Clopidogrel efficacy is lower in hemodynamically unstable MI patients. Insufficient absorption and biotransformation of clopidogrel due to splanchnic and liver ischemia might be the cause of this fact.