Anticoagulation is recommended for all NSTE‐ACS patients undergoing PCI to reduce the risk of intracoronary and catheter thrombus formation. The type of anticoagulation is selected according to ischemic and bleeding risks as well as the efficacy–safety profile of the chosen agent for each patient individually. Options for parenteral anticoagulants for patients with NSTE‐ACS undergoing PCI include unfractionated heparin (UFH), low molecular weight heparin (LMWH, usually enoxaparin), bivalirudin, and fondaparinux.
Unfractionated heparin has been used for many years in PCI and is currently being used in the vast majority of patients. It has low cost; however, response to unfractionated heparin is variable, requiring measurement of its antithrombotic effect. In the largest study of enoxaparin in NSTE‐ACS, the Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial, 10 027 high risk NSTE‐ACS patients treated with an early invasive strategy were randomized to enoxaparin or UFH. Enoxaparin‐treated patients had similar incidence of death or MI compared with those treated with UFH, but higher incidence of major bleeding [56]. Consequently, enoxaparin is infrequently used during PCI for NSTE‐ACS, although it may be considered for those pre‐treated with subcutaneous enoxaparin [57].
Fondaparinux is a factor Xa inhibitor. In the OASIS 5 trial, patients receiving fondaparinux had lower 30‐day mortality compared with those receiving enoxaparin (2.9% vs 3.5%; p = 0.02), likely related to the lower risk for major bleeding at nine days (2.2% vs 4.1%; p < 0.001). However, the fondaparinux arm had a threefold higher rate of guide catheter thrombus (0.9% vs 0.4%; p=0.001), hence UFH (85 IU/kg without or 60 IU/kg with a GP IIb/IIIa inhibitor) [58] should be administered to patients on fondaparinux undergoing PCI [13,14].
Finally, bivalirudin is a direct thrombin inhibitor that may be considered as an alternative to UFH for certain patients. In the ACUITY trial, bivalirudin monotherapy was associated with a non‐inferior rate of the composite ischemia endpoint (death, MI, or unplanned revascularization) (7.8% and 7.3%, respectively; p = 0.32) and significantly lower rates of major bleeding (3.0% vs 5.7%; p < 0.001) as compared with bivalirudin + GP IIb/ IIIa inhibitor and UFH + GP IIb/IIIa inhibitor. However, among patients not pretreated with clopidogrel before PCI, the incidence of ischemic events was higher in the bivalirudin group (9.1% vs 7.1%, RR 1.29; p = 0.054 for interaction) [59,60]. The Bivalirudin versus Heparin monotherapy in patients with NSTEMI (VALIDATE‐SWEDEHEART) trial randomized 6,006 patients with acute MI to bivalirudin versus heparin monotherapy. After a six month follow‐up period both groups had similar incidence of death, MI, or major bleeding [61]. This finding was consistent with the results of the MATRIX trial [62]. As a result, bivalirudin is currently used very infrequently, mainly in patients with heparin‐induced thrombocytopenia. Pre‐ and periprocedural pharmacotherapy recommendations from the United States (2014) and Europe (2018) for NSTE‐ACS patients are summarized in Table 12.2.
Table 12.2 Guideline recommendations on pre‐ and periprocedural therapy for NSTE‐ACS patients.
| ACC/AHA Guidelines | ESC Guidelines |
|---|---|
| Antiplatelet therapy | |
| 1. Aspirin is recommended for all patients at an initial dose of 81–325 mg (325 mg if not already on aspirin prior to PCI) (class I) | 1. Aspirin is recommended for all patients without contraindications at an initial oral loading dose of 150–300 mg (or 80–150 mg IV), regardless of treatment strategy (class I). |
| 2. A P2Y12 inhibitor is recommended in addition to ASA (class I). Options include:Prasugrel 60 mg loading doseTicagrelor 180 mg loading doseClopidogrel 600 mg loading dose Ticagrelor is preferred to clopidogrel in patients treated with an early invasive strategy and/or stenting (class IIA), Prasugrel is preferred over clopidogrel in patients not at high risk of bleeding (class IIA), and without a history of stroke or TIA (class III) | 2. A P2Y12 inhibitor is recommended in addition to ASA (class I). Options include:Prasugrel (60mg loading dose) in P2Y12 naïve patients undergoing PCI (class I). Prasugrel should be avoided if coronary anatomy is not known (class III).Ticagrelor (180mg loading dose) irrespective of prior P2Y12 therapy (class I).Clopidogrel (300–600mg loading dose), when ticagrelor and prasugrel are not available or contraindicated (class I). For pretreatment ticagrelor (180mg loading dose) or clopidogrel (600mg loading dose) if ticagrelor is not available should be considered (class IIa). |
| 3. GP IIb/IIIa inhibitors are recommended in patients with NSTE‐ACS and high risk features (e.g. high troponin) not adequately pretreated with clopidogrel or ticagrelor (class I) or in high risk patients on UFH and adequately pretreated with clopidogrel (class IIa). Options include: • Eptifibatide • Tirofiban | 3. GP IIb/IIIa inhibitors should be considered for bail out if there is evidence of no‐reflow or a thrombotic complication (class IIa), may be considered in P2Y12 naïve patients undergoing PCI (class IIb), and should be avoided if coronary anatomy is not known (class III). Options include: Eptifibatide Tirofiban |
| 4. Cangrelor may be considered in P2Y12 naïve patients undergoing PCI (class IIb). | |
| Anticoagulation therapy | |
| 1. Intravenous UFH is useful in patients with NSTE‐ACS undergoing PCI (class I) and If PCI is performed while the patient is on fondaparinux, an additional 85 IU/kg UFH should be given intravenously immediately before PCI because of the risk of catheter thrombosis (60 IU/kg IV if a GP IIb/IIIa inhibitor used with UFH) (class I) | 1. UFH is recommended (class I) and in patients on fondaparinux (2.5 mg/day), a single bolus UFH (85 IU/kg, or 60 IU/kg in the case of concomitant use of GP IIb/IIIa receptor inhibitors) is indicated during PCI (class I). |
| 2. Performance of PCI with enoxaparin may be reasonable in patients treated with upstream subcutaneous enoxaparin for NSTE‐ACS (class IIb) | 2. Enoxaparin should be considered in patients pretreated with subcutaneous enoxaparin (class IIa). |
| 3. Fondaparinux should not be used as the sole anticoagulant to support PCI in patients with NSTE‐ACS due to an increased risk of catheter thrombosis (class III) | Crossover of UFH and LMWH is not recommended (class III). |
| 4. Bivalirudin is useful as an anticoagulant with or without prior treatment with UFH in NSTE‐ACS patients undergoing PCI (class I)For patients who have received UFH, wait 30 min, then give 0.75 mg/kg IV loading dose, then 1.75 mg/kg/h IV infusionFor patients already receiving bivalirudin infusion, give additional loading dose 0.5 mg/kg and increase infusion to 1.75 mg/kg/h during PCI In patients with NSTE‐ACS undergoing PCI who are at high risk of bleeding, bivalirudin monotherapy is preferred to the combination of UFH and a GP IIb/IIIa receptor antagonist (class IIa) | 3. Bivalirudin (0.75 mg/kg bolus, followed by 1.75 mg/kg/h for up to 4 h after the procedure) may be considered as alternative to UFH (class IIb) |
Conclusions
In summary, NSTE‐ACS are commonly encountered in daily clinical practice. Risk stratification is key for determining optimal treatment strategies, with higher risk patients deriving more benefit from an early invasive