Anti-thrombotic Therapy With Cangrelor and Bivalirudin in Venoarterial Extracorporeal Membrane Oxygenation Patients Undergoing Percutaneous Coronary Intervention: A Single-Center Experience

Abstract

VA-ECMO is commonly used for patients in cardiogenic shock (CS) or refractory cardiac arrest (CA) undergoing PCI for ACS. In this setting at high risk of both thrombotic and hemorrhagic complications, optimal anti-thrombotic therapy remains ill-defined. We hypothesized that an anti-thrombotic therapy comprising a parenteral anticoagulant (bivalirudin) and a parenteral anti-platelet agent (cangrelor) may prove safe and effective in this scenario. From November 2019 to December 2021, 14 patients received at least one dose of cangrelor (starting dose: 0.125 μg/kg/min) plus bivalirudin, without background aspirin, in the context of PCI and VA-ECMO for ACS-related CS/CA, and were included in this study. Efficacy endpoint was occurrence of thrombotic events and safety endpoint was major bleeding occurrence. Median age was 58 years. The majority (64%) presented with refractory CA. A thrombotic event occurred in 14%, while major bleeding occurred in 21% patients. One patient experienced arterial thrombosis after VA-ECMO arterial cannula removal, another experienced ischemic cerebellar stroke without functional sequelae. Bleeding events were: 29% BARC 3a, 14% BARC 3b, and 7% BARC 5b. Overall in-hospital mortality was 50%. Cangrelor was continued for 5 (4–10) days; temporary discontinuation was necessary in 36%, either for VA-ECMO cannula removal or for bleeding events. A low dose of cangrelor, associated with standard-intensity anticoagulation with bivalirudin was a feasible anti-thrombotic strategy in patients undergoing PCI during VA-ECMO support for ACS-related CS/CA. Bleeding events rates outweighed thrombotic events rates in this critically-ill population, although the observed rates were lowest among available studies.

Antithrombotic Stewardship: Evaluation of Platelet Reactivity-Guided Cangrelor Dosing Using the VerifyNow Assay

“…Previous studies also report low incidence of cardiovascular events of 0%-3% with cangrelor bridging, even in high-risk populations. 3,4,6,8,15,16 Our study included patients at high risk of ST, with 54% undergoing PCI during the index hospitalization, and 63 patients (68%) placed on cangrelor within 2 weeks of PCI. In addition, the median SOFA score of 5 and high rates of MCS (46 patients, 50%) further highlights the degree of critical illness in our cohort, increasing not only the ischemic risk but also the bleeding risk.…”

“…2 The use of cangrelor in those in cardiogenic shock and/or requiring MCS has been reported to increase the bleeding risk. 4,10,13,16 The elevated bleed event rate of 23% can be attributed to the high-risk profile of our patient population, which includes patients admitted to an ICU, those in cardiogenic shock, and those receiving MCS. We observed major bleeding to occur at a higher incidence in those on MCS at 33%, similar to rates described in other retrospective cohorts of 31%-42%.…”

“…We observed major bleeding to occur at a higher incidence in those on MCS at 33%, similar to rates described in other retrospective cohorts of 31%-42%. 4,6,10,13,15,16 Patients requiring MCS represent the highest risk for bleeding with cangrelor bridging, and assessing the full antithrombotic regimen, including concomitant antiplatelet and anticoagulant therapy, may be necessary. 4,13,16 In at least 1 retrospective cohort, a perceived reduction in bleeding was believed to be associated with the use of lower doses of cangrelor (0.125-0.57 mg/kg/min) and bivalirudin while holding aspirin.…”

“…4,6,10,13,15,16 Patients requiring MCS represent the highest risk for bleeding with cangrelor bridging, and assessing the full antithrombotic regimen, including concomitant antiplatelet and anticoagulant therapy, may be necessary. 4,13,16 In at least 1 retrospective cohort, a perceived reduction in bleeding was believed to be associated with the use of lower doses of cangrelor (0.125-0.57 mg/kg/min) and bivalirudin while holding aspirin. 16 Contemporary cardiac stents seem to facilitate earlier endothelization, between 1 and 6 months, allowing for shorter, less intensified DAPT.…”

“…4,13,16 In at least 1 retrospective cohort, a perceived reduction in bleeding was believed to be associated with the use of lower doses of cangrelor (0.125-0.57 mg/kg/min) and bivalirudin while holding aspirin. 16 Contemporary cardiac stents seem to facilitate earlier endothelization, between 1 and 6 months, allowing for shorter, less intensified DAPT. 17 With the advancements in stent technology, there may be a greater interest in preventing bleeding complications while still maintaining adequate platelet inhibition.…”