A reduced, tailored dose of cangrelor combined with bivalirudin achieved consistent platelet inhibition with 0 major bleeding or MACE events in 5 OHCA-AMI-CS patients requiring VA-ECMO.
Does a reduced, tailored cangrelor dose plus bivalirudin prevent thrombotic and bleeding events in OHCA-AMI-CS patients requiring VA-ECMO and pPCI?
A dual regimen of low-dose cangrelor and bivalirudin achieved consistent platelet inhibition without major bleeding or MACE in a preliminary series of 5 critically ill OHCA-AMI-CS patients on VA-ECMO.
Abstract Introduction In Out-of-Hospital Cardiac Arrest (OHCA)/Acute Myocardial Infarction– Cardiogenic Shock (AMI-CS) requiring primary PCI and Veno-Arterial ExtraCorporeal Membrane Oxygenation (VA-ECMO), antithrombotic therapy is challenging due to competing thrombotic and bleeding risks and post-OHCA coagulopathy with associated platelet dysfunction. Early clinical data suggest that combination of a individually tailored Cangrelor dosing regimen based on Multiplate test results, combined with background bivalirudin anticoagulation, may be equally effective but safer in terms of bleeding risk than triple therapy (acetylsalicylic acid, P2Y12 inhibitor and anticoagulation) in this setting (1). We designed the SURVIVE phase-2, single-arm prospective clinical trial to assess efficacy and safety of a reduced, adjustable-dose Cangrelor regimen plus Bivalirudin in patients with OHCA and AMI-CS requiring VA-ECMO. Efficacy and safety endpoints were defined as thrombotic and bleeding (BARC ≥3b) adverse events occurring during Cangrelor infusion. Methods We report data from the first 5 consecutive OHCA-AMI-CS patients requiring VA-ECMO and who underwent pPCI treated with reduced, tailored Cangrelor dose (starting dose: 0.125 μg/kg/min without initial bolus) targeting an ADP test value 46 U in combination with bivalirudin (without bolus) with an aPTT target of 55-70 seconds. Aspirin was not administered. Platelet function was monitored using the Multiplate test at predefined timepoint (baseline, 30 min, 12 hours, every 24 hours and after any Cangrelor dose adjustment) and routine laboratory testing, including coagulation profile, was performed every 6 hours. Cangrelor dose adjustments were allowed in increments of ±0.125 μg/kg/min. Results Across platelet function assays (mean number of Multiplate tests per patient: 7) at different timepoints, 100% of ADP-test values were in target range (46 U) and no adjustments in Cangrelor infusion rate (dose: 0.125 μg/kg/min) were required. In these first 5 patients, coronary angiography showed multivessel disease, and PCI was performed only on the culprit lesion. Interestigly, the median ADP test value at baseline (T0, prior to any anti- thrombotic therapy) was 17 U, suggesting a suppressed platelet function at admission. No major bleeding (BARC ≥3b) events occurred and no MACE (in-stent thrombosis, new myocardial infarction) were documented. One ischemic stroke occurred in the context of a vascular complication requiring surgery during ECLS instituted as part of initial resuscitation. Conclusions In this preliminary series, a dual regimen comprising low-dose cangrelor and bivalirudin achieved consistent platelet inhibition in OHCA-AMI-CS patients undergoing pPCI during VA-ECMO support. The presence of platelet dysfunction at admission supports the rationale for a lighter antithrombotic therapy, as triple therapy may expose these critically-ill patients to an excess bleeding risk.
Pieri et al. (Sun,) conducted a other in Out-of-Hospital Cardiac Arrest (OHCA) / Acute Myocardial Infarction-Cardiogenic Shock (AMI-CS) requiring primary PCI and VA-ECMO (n=5). Cangrelor plus Bivalirudin was evaluated on Thrombotic and bleeding (BARC ≥3b) adverse events occurring during Cangrelor infusion. A reduced, tailored dose of cangrelor combined with bivalirudin achieved consistent platelet inhibition with 0 major bleeding or MACE events in 5 OHCA-AMI-CS patients requiring VA-ECMO.