An important consideration for HCR is the anti-coagulation and platelet inhibition strategy as the risk of surgical bleeding has to be balanced with the risk of stent thrombosis [19]. These considerations are most relevant when HCR is performed in a same-session approach or when PCI has been performed prior to the surgical revascularization arm.

Unfractionated heparin is the most commonly used anti-coagulant for both PCI and CABG procedures as anti-coagulant effect can be monitored by measuring activated clotting times (ACTs) and can be reversed with protamine. Low-molecular weight heparin is a less attractive option for cardiac surgery, limited by its long half-life and irreversibility. Typical heparin reversal with protamine is performed post-bypass, which can be problematic in an HCR approach when surgical revascularization is performed after PCI, as there is a theoretical risk of stent-thrombosis with protamine administration. Interestingly, in a series comparing same-session performed HCR without protamine reversal versus standard off-pump CABG, less bleeding was noted in the HCR cohort [18]. This finding was attributed to lesser bleeding associated with minimally-invasive surgical techniques. The direct thrombin inhibitor, Bivalirudin has been evaluated as an anti-coagulation strategy in HCR with mid-CAB with demonstrated efficacy by Kiaii and colleagues [20]. In this series, Bivalirudin was administered intraoperatively during the mid-CAB of same-session HCR and continued for the PCI of the revascularization. The optimal anti-coagulation strategy has not been determined in HCR.

Anti-platelet therapy is an additional consideration during HCR as PCI requires dual anti-platelet therapy (DAPT) with aspirin and an oral thienopyridine such as Clopidogrel which works at the platelet P2Y ADP receptor site. Continued DAPT through the surgical revascularization period when PCI is performed first clearly has implications for bleeding risk. Platelet inhibition strategy is most complex in the same-session approach as the timing interval between both revascularization periods is minimal. The timing of administration of a loading dose of a thienopyridine and protamine reversal are particularly relevant. Diverse strategies have been successfully implemented without a consensus in the literature regarding the ideal approach. Reicher and colleagues performed mid-CAB followed by PCI without protamine reversal with Clopidogrel loading immediately after PCI. In their series, they documented adequate platelet inhibition by 24 h by ADP-induced aggregation [8]. Zhao and colleagues have successfully used the strategy of administering a 300 mg loading dose of Clopidogrel just prior to PCI followed immediately by CABG with subsequent protamine reversal [21]. At our institution (University of Maryland), a strategy of CABG first followed by protamine reversal of heparin with subsequent re-heparinization and clopidogrel loading via NG tube for PCI after CABG has been used successfully in a same-session approach.

The optimal sequence of revascularization in HCR is not arbitrary as there are advantages and disadvantages inherent to the three potential revascularization approaches: Surgery prior to PCI versus PCI prior to surgery versus a same-session intervention where both revascularization procedures are performed in the same procedural setting with either procedure being performed first. Notably, patient presentation often dictates intervention sequence.