Pharmacodynamic Effects of a 6-Hour Regimen of Enoxaparin in Patients Undergoing Primary Percutaneous Coronary Intervention (PENNY PCI Study)

Abstract

Delayed onset of action of oral P2Y₁₂ inhibitors in ST-elevation myocardial infarction (STEMI) patients may increase the risk of acute stent thrombosis. Available parenteral anti-thrombotic strategies, to deal with this issue, are limited by added cost and increased risk of bleeding. We investigated the pharmacodynamic effects of a novel regimen of enoxaparin in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Twenty patients were recruited to receive 0.75 mg/kg bolus of enoxaparin (pre-PPCI) followed by infusion of enoxaparin 0.75 mg/kg/6 h. At four time points (pre-anti-coagulation, end of PPCI, 2-3 hours into infusion and at the end of infusion), anti-Xa levels were determined using chromogenic assays, fibrin clots were assessed by turbidimetric analysis and platelet P2Y₁₂ inhibition was determined by VerifyNow P2Y12 assay. Clinical outcomes were determined 14 hours after enoxaparin initiation. Nineteen of 20 patients completed the enoxaparin regimen; one patient, who developed no-reflow phenomenon, was switched to tirofiban after the enoxaparin bolus. All received ticagrelor 180 mg before angiography. Mean (± standard error of the mean) anti-Xa levels were sustained during enoxaparin infusion (1.17 ± 0.06 IU/mL at the end of PPCI and 1.003 ± 0.06 IU/mL at 6 hours), resulting in prolonged fibrin clot lag time and increased lysis potential. Onset of platelet P2Y₁₂ inhibition was delayed in opiate-treated patients. No patients had thrombotic or bleeding complications. In conclusion, enoxaparin 0.75 mg/kg bolus followed by 0.75 mg/kg/6 h provides sustained anti-Xa levels in PPCI patients. This may protect from acute stent thrombosis in opiate-treated PPCI patients who frequently have delayed onset of oral P2Y₁₂ inhibition.

Fig. 1

Anti-Xa levels. A scatter plot demonstrating anti-Xa levels throughout the studied time points ( n  = 19). Variance during the infusion was assessed using one-way analysis of variance (ANOVA). Six hours versus 2 to 3 hours; p  = 0.6 and 6 hours versus post-PCI; p  = 0.09. Error bars represent mean ± standard error of the mean (SEM).

Fig. 2

The effects of enoxaparin on fibrin clot properties. Scatter plots demonstrating fibrin clot properties pre- and throughout treatment with enoxaparin. Error bars represent mean ± standard error of the mean (SEM). AU, arbitrary unit; PPCI, primary percutaneous coronary intervention. *** denotes p  < 0.001, ** denotes p  < 0.01, * denotes p  = 0.01; all compared with baseline (T1) and calculated using Dunnett's multiple comparisons tests.

Fig. 3

Platelet P2Y ₁₂ inhibition. ( A ) Scatter plot demonstrating the corresponding P2Y ₁₂ reaction units throughout the studied time points. Error bars represent mean ± standard error of the mean (SEM). ( B ) Bar graph highlighting the number of patients with 0% inhibition as determined by VerifyNow. Two patients did not receive opiates and had > 20% inhibition by the end of PCI (as indicated by arrow).