Antithrombin therapy to support PCI

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Anahita Deylamsalehi, M.D.[2]

Antithrombin Therapy to Support PCI

Drug For Patients Who Received Previous Anticoagulant Therapy For Patients Who Did Not Received Any Anticoagulant Therapy
UFH Additional UFH as needed (e.g., 2000 – 5000 U) to achieve the activated clotting time (ACT) of 250-300 seconds. 70–100 U/kg initial bolus to achieve the target ACT of 250–300 seconds.
Enoxaparin *An intravenous dose of 0.3 mg/kg of enoxaparin for patients who received previous treatment with subcutaneous tissue enoxaparin within the last 8 –12 hours. 0.5 – 0.75 mg/kg intravenous bolus
Bivalirudin For patients who have received UFH, repeat ACT, if ACT is not in the therapeutic range, then give a 0.75 mg/kg intravenous bolus, then continue with a 1.75 mg/kg/h intravenous infusion. 0.75 mg/kg bolus, then continue with a 1.75 mg/kg/h intravenous infusion.
Argatroban 200 mg/kg intravenous bolus, then continue with a 15 mg/kg/min intravenous infusion. 350 mg/kg, then continue with a 15 mg/kg/min intravenous infusion.

HemoTec (GmbH, Switzerland) or I-Stat (Abbott) device can be used to check activated clotting time (ACT) for UFH dosing. However, activated clotting time (ACT) goals are 50 seconds higher for Hemochron ACT (Werfen) devices. Furthermore, it is recommended to consider the higher target ACT in patients with chronic total occlusion. On the other hand, target ACT should be 200-250 seconds if a intravenous glycoprotein IIb/IIIa inhibitors is selected.[8][9][10][11][12][13]

Unfractionated Heparin (UFH)

Mechanism of action

Heparin is a glycosaminoglycan of 12-15 kDa that binds Anti-thrombin 3 and facilitates its ability to inhibit coagulation factors 2a (thrombin) and 10a by a factor of 1000. Thrombin plays a central role not only in plasma coagulation (by catalysing fibrinogen to fibrin as well as activating several coagulation factors) but platelet activation as well.

Advantages

and 250-350 without 2b/3a (these levels have been empirically derived and target ACT's have fallen in the stent era as the risk for acute vessel closure has diminished)

Disadvantages

Low Molecular Weight Heparinoids (LMWH)

Mechanism of Action

Advantages

Disadvantages

Trials with Bivalirudin

Replace 2: This trial compared bivalirudin plus provisional 2b/3a (which ended up being given in 7.2% of patients) vs heparin with planned 2b/3a. In this study of 6010 patients, ischemic events were similar but major bleeding (mostly vascular access site) was reduced by about 40%. There was no mortality difference at one year despite a 0.8% absolute increase in peri-procedural MI's in the bivalirudin group. Importantly ,85% of patients were pre-treated with plavix or ticlid. In Replace 2, bivalirudin strategy was found to be less expensive because of savings on 2b/3a as well as less bleeding.

ACUITY: Complex trial of 13,819 high risk UA or NSTEMI patients undergoing early invasive strategy comparing bivalirudin alone vs Bivalirudin with 2b/3a vs Heparin or Lovenox with 2b/3a. It was found that the ischemic composite endpoint (death, MI, revascularization) at 30 days was the same in all 3 arms. However, major bleeding was significantly less with bivalirudin alone at 3.1% vs bivalirudin and 2b/3a at 5.3% vs Heparin, Lovenox and 2b/3a at 5.7%. Again this was driven mostly by access site complications, but unlike in REPLACE 2 the bleeding endpoints were significant whether one used the study definition or TIMI definition. A major caveat is also that patients who did not get plavix had increased ischemic events in the bivalirudin only arm.

CONCLUSION: Bivalirudin is an excellent choice in most NSTEMI/UA patients managed with an early invasive strategy if they have been pre-treated with clopidogrel. If this has not been done then 2b/3a will need to be used and the benefits of bivalirudin are greatly attenuated.

2021 ACA Revascularization Guideline

Class 1 Recommendation, Level of Evidence: C-EO[1]
Administration of intravenous unfractionated heparin (UFH) is useful in reducing ischemia events in patients undergoing PCI.
Class 1 Recommendation, Level of Evidence: C-LD[1][18][19]
Bivalirudin or argatroban should be used instead of UFH in patients with heparin-induced thrombocytopenia who are undergoing PCI.
Class 2b Recommendation, Level of Evidence: A[1][20][21][22][23][24][25][26][27][28][29]
Bivalirudin could be used as a reasonable alternative to UFH in order to reduce bleeding in patients undergoing PCI.
Class 2b Recommendation, Level of Evidence: B-BR[1][30][31][32][33][34]
In patients who have been treated with upstream subcutaneous enoxaparin for either unstable angina or NSTE-ACS, intravenous enoxaparin could be considered at the time of PCI in order to reduce ischemic events.
Class 3 Recommendation (HARM), Level of Evidence: B-R[1][31][35][36]
UFH should be avoid in patients who are on therapeutic subcutaneous enoxaparin, and have received the last dose within 12 hours of PCI due to higher rate of bleeding.

ACCF/AHA/SCAI 2011 Guidelines for Percutaneous Coronary Intervention (DO NOT EDIT)[37]

Use of Parenteral Anticoagulants during PCI (DO NOT EDIT)[37]

Class I
"1. An anticoagulant should be administered to patients undergoing PCI. (Level of Evidence: C)"

Unfractionated Heparin (DO NOT EDIT)[37]

Class I
"1. Administration of intravenous UFH is useful in patients undergoing PCI. (Level of Evidence: C)"

Enoxaparin (DO NOT EDIT)[37]

Class I
"1. An additional dose of 0.3 mg/kg intravenous enoxaparin should be administered at the time of PCI to patients who have received fewer than 2 therapeutic subcutaneous doses (e.g., 1 mg/kg) or received the last subcutaneousenoxaparin dose 8 to 12 hours before PCI.[31][38][39][6][7](Level of Evidence: B)"
Class III (Harm)
"1. Unfractionated heparin (UFH) should not be given to patients already receiving therapeutic subcutaneous enoxaparin.[31][35](Level of Evidence: B)"
Class IIb
"1. Performance of PCI with enoxaparin may be reasonable in patients either treated with upstream subcutaneous enoxaparin forUA/NSTEMI or who have not received prior antithrombin therapy and are administered intravenous enoxaparin at the time ofPCI.[40][41][31][42] (Level of Evidence: B)"

Bivalirudin and Argatoban (DO NOT EDIT)[37]

Class I
"1. For patients undergoing PCI, bivalirudin is useful as an anticoagulant with or without prior treatment with unfractionated heparin (UFH).[43][44][20][45][46][47][48][26][49](Level of Evidence: B)"
"2. For patients with heparin-induced thrombocytopenia, it is recommended that bivalirudin or argatroban be used to replace unfractionated heparin (UFH).[18][19] (Level of Evidence: B)"

Fondaparinux (DO NOT EDIT)[37]

Class III (No Benefit)
"1. Fondaparinux should not be used as the sole anticoagulant to support PCI. An additional anticoagulant with anti-IIa activity should be administered because of the risk of catheter thrombosis.[2][3](Level of Evidence: C)"

References

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