Only 22.2% of patients were restarted on eptifibatide following surgery. All 4 patients resumed the 2 mcg/kg/min maintenance dose with only 2 of the 4 patients receiving a loading dose of 180 mcg/kg. Two patients did not restart an oral P2Y12-receptor antagonist after surgery. Overall only 50% of patients received a loading dose of an oral P2Y12-receptor antagonist after surgery and 88.9% of patients started on a maintenance dose of the oral P2Y12-receptor antagonist. One patient was discharged on aspirin and warfarin combination therapy, while another only on aspirin monotherapy.
There were no systemic thromboembolic or stent thrombosis events in our patient population. One patient (patient 11) had a TIMI major bleeding event. This patient had a pericardial hematoma that required 8 units of packed red blood cells to be transfused and reoperation for resolution. This adverse event occurred on postoperative day 2. In addition, there was one documented TIMI minimal gastrointestinal bleed on postoperative day 6 (patient 10) in which the patient received 2 units of packed red blood cells. Both of these patients were on concurrent therapeutic heparin infusions at the time of the bleeding event. One patient died within 90 days of surgery due to cancer.
In this descriptive report, we found that antiplatelet therapy management in patients undergoing surgery within 1 year of intracoronary stent implantation was highly variable in the perioperative period. Half of patients did not continue aspirin throughout the surgery, 27.8% of patients stopped antiplatelet therapy less than 5 days before surgery, 27.8% did not receive a glycoprotein IIb/IIIa loading dose, and 61.1% of patients did not receive eptifibatide for the recommended duration of at least 3 days before procedure. After surgery 50% of patients did not receive a loading dose of an oral P2Y12-receptor antagonist.
Stent thrombosis has been reported to occur as frequently as 2% within the first year following implantation and is associated with a morbidity and mortality risk up to 45%.13 Our study focused on 18 individuals with intracoronary stent implantation within the past year who were bridged with eptifibatide for antiplatelet therapy. Currently, there is no consensus on guidelines for perioperative management of antiplatelet therapy.14,15 In the event that surgery cannot be postponed, the American College of Chest Physicians recommends discontinuation of DAPT around the time of surgery rather than stopping 7 to 10 days prior.5 In contrast, the American College of Cardiology/American Heart Association guidelines recommend stopping clopidogrel or ticagrelor 5 days and prasugrel 7 days before surgery in patients with a high risk of bleeding and those undergoing elective coronary bypass graft surgery.14,15 Furthermore, recent expert opinions suggest that a loading dose of eptifibatide may not be required for bridging in the absence of a need for immediate effect.16 The differences in recommendations appear largely due to the lack of evidence surrounding the use of short-acting intravenous GP IIb/IIIa inhibitors, such as eptifibatide or tirofiban, in the perioperative setting.5
Despite concerns of stent thrombosis caused by early interruption of antiplatelet therapy, the available data for periprocedural antiplatelet management are limited. One study reviewed 19 patients bridged with eptifibatide. Clopidogrel was stopped a mean of 6 days before the procedure, and 2 days before initiating eptifibatide infusion. Eptifibatide was stopped a mean of 10 hours before the procedure. Major bleeding occurred in 7/13 (53.9%) of cardiac surgery patients and no bleeding events were reported in noncardiac surgery patients. They also reported no thrombotic events.13 Another study also discontinued clopidogrel 5 days before the procedure and began a tirofiban infusion 2 to 3 days before surgery. Tirofiban was stopped approximately 4 hours before the procedure. Six major bleeding events were reported, only 2 (33.3%) corresponding with coronary artery bypass surgery. This study also reported no thrombotic events.17 The largest safety study to date analyzed 71 propensity matched patients who were bridged for surgery with eptifibatide for cardiovascular surgery and found that there was no increase in bleeding or any incidence of stent thrombosis in patients who were bridged compared to those who discontinued P2Y12 inhibitor therapy greater than 5 days prior to surgery but were not initiated on bridging therapy. The authors of this study observed an increased rate of transfusion requirements in patients who were bridged with eptifibatide and received concurrent aspirin and/or heparin.18 Both patients who experienced a bleeding event in our report were on therapeutic heparin infusions and aspirin therapy at the time of the event.
A recent metaanalysis of perioperative bridging in patients with coronary stents undergoing surgery included 8 studies with 280 patients and found stent thrombosis occurred in 1.3% of patients and major bleeding events in 7.4% of patients. Notably, the occurrence of stent thrombosis in the metaanalysis is driven by a single study in which 3 patients had a stent thrombosis in the setting of antiplatelet therapy interruption. In all 3 cases, both aspirin and clopidogrel were discontinued before surgery, contrary to our recommended protocol of continuing aspirin through the procedure while holding P2Y12 inhibitors. The authors concluded that perioperative bridging with a GP IIb/IIIa inhibitor did not eliminate stent thrombosis risk and may increase the risk for bleeding.19
A recent report reviewed a Massachusetts administrative claims database of 1838 BMS and 3565 DES patients requiring surgery within 12 months of stent placement.20 Through propensity score matching analyses, investigators determined that the incidence of adverse effects was significantly lower beyond 90 days after DES placement compared to BMSs and it may not be necessary to wait until 12 months after DES placement before performing noncardiac surgical procedures. From these reports, GP IIb/IIIa inhibitors have been effective at preventing stent thrombosis but with an associated bleeding risk.
GP IIb/IIIa inhibitors are advantageous for bridging antiplatelet therapy because of their short half-lives compared to aspirin and P2Y12 receptor antagonists. Cangrelor is a new direct P2Y12 platelet-receptor inhibitor with a short half-life and rapid onset. Normal platelet function is fully restored within 1 hour after discontinuation of infusion. Cangrelor has been recently approved by the Food and Drug Administration for PCI and may be a promising agent for perioperative use, though the dose studied for bridging is lower than the approved dose used for PCI.21,22 Also under development are new coronary stents with potentially lower rates of stent thrombosis. Strategies include bioresorbable stents and stents coated with antiplatelet drugs.23
The major limitation to our report is that there were no comparator groups to identify causality of outcomes related to eptifibatide bridging. In addition, there were a small number of patients identified and not all patients were treated uniformly. Few patients had received a BMS and variations in treatment strategies were common.
Management of patients requiring surgery less than 1 year after coronary stent placement with antiplatelet, anticoagulant, and aspirin remains complex. There is variation between patients on whether aspirin is continued through the procedure, the time between discontinuation of antiplatelet agents and surgery, and whether or not a patient receives a loading dose of eptifibatide for bridging or antiplatelet agent postprocedure. Prospective randomized-controlled trials would better define the risks and benefits of perioperative bridging and such trials are needed. Until then, standardizing therapy according to patient risk for thrombosis and bleeding might help optimize outcomes.
Dr. Deepak L. Bhatt discloses the following relationships - Advisory Board: Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care; Chair: American Heart Association Quality Oversight Committee; Data Monitoring Committees: Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Vice-Chair), VA CART Research and Publications Committee (Chair); Research Funding: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Medtronic, Pfizer, Roche, Sanofi Aventis, The Medicines Company; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); Site Co-Investigator: Biotronik, Boston Scientific, St. Jude Medical; Trustee: American College of Cardiology; Unfunded Research: FlowCo, PLx Pharma, Takeda. The other authors have no conflicts of interest to disclose.
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Keywords:Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved
antiplatelet therapy; bridging; eptifibatide